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MayoTestCatalog Rochester SortedByTestName Duplex Interpretive PDF
MayoTestCatalog Rochester SortedByTestName Duplex Interpretive PDF
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Policies Mayo Medical Laboratories [POL 056279.001] Effective Date: 05/18/2015
POLICY STATEMENTS
Animal Specimens
We do not accept animal specimens for laboratory testing.
Billing
ClientEach month you will receive an itemized invoice/ statement which will indicate the date of service,
patient name, CPT code, test name, and test charge. Payment terms are net 30 days. When making payment,
please include our invoice number on your check to ensure proper credit to your account.
PatientMayo Medical Laboratories does not routinely bill patients insurance; however, if you have made
advanced arrangements to have Mayo Medical Laboratories bill your patients insurance, please include the
following required billing information: responsible party, patients name, current address, zip code, phone
number, Social Security number, and diagnosis code. Providing this information will avoid additional
correspondence to your office at some later date. Please advise your patients that they will receive a bill for
laboratory services from Mayo Medical Laboratories for any personal responsibility after insurance payment.
VISA and MasterCard are acceptable forms of payment.
BillingCPT Coding
It is your responsibility to determine correct CPT codes to use for billing. While this catalog lists CPT codes in
an effort to provide some guidance, CPT codes listed only reflect our interpretation of CPT coding requirements
and are not necessarily correct. Particularly, in the case of a test involving several component tests, this catalog
attempts to provide a comprehensive list of CPT codes for all of the possible components of the test. Only a
subset of component tests may be performed on your specimen. You should verify accuracy of codes listed.
Where multiple codes are listed, you should select codes for tests actually performed on your specimen. MAYO
MEDICAL LABORATORIES ASSUMES NO RESPONSIBILITY FOR BILLING ERRORS DUE TO
RELIANCE ON CPT CODES LISTED IN THIS CATALOG. For further reference, please consult the CPT
Coding Manual published by the American Medical Association. If you have any questions regarding use of a
code, please contact your local Medicare carrier.
Cancellation of Tests
Cancellations received prior to test setup will be honored at no charge. Requests received following test setup
cannot be honored. A report will be issued automatically and charged appropriately.
Chain-of-Custody
Chain-of-custody, a record of disposition of a specimen to document who collected it, who handled it, and who
performed the analysis, is necessary when results are to be used in a court of law. Mayo Medical Laboratories
has developed packaging and shipping materials that satisfy legal requirements for chain-of-custody. This
service is only offered for drug testing. 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com
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Compliance Policies
Mayo Medical Laboratories is committed to compliance with applicable laws and regulations such as the
Clinical Laboratory Improvement Amendments (CLIA). Regulatory agencies that oversee our compliance
include, but are not limited to, the Centers for Medicare and Medicaid Services (CMS), the Food and Drug
Administration (FDA), and the Department of Transportation (DOT). Mayo Medical Laboratories develops,
implements, and maintains policies, processes, and procedures throughout our organization which are designed
to meet relevant requirements. We expect clients utilizing our services will ensure their compliance with patient
confidentiality, diagnosis coding, anti-kick back statutes, professional courtesy, CPT-4 coding, CLIA
proficiency testing, and other similar regulatory requirements. Also see Accreditation and Licensure, HIPAA
Compliance, and Reportable Disease.
Confidentiality of Results
Mayo Medical Laboratories is committed to maintaining confidentiality of patient information. To ensure
Health Insurance Portability and Accountability Act of 1996 (HIPAA) and the College of American
Pathologists (CAP) compliance for appropriate release of patient results, Mayo Medical Laboratories has
adopted the following policies:
Under federal regulations, we are only authorized to release results to ordering physicians or health care
providers responsible for the individual patients care. Third parties requesting results including requests
directly from the patient are directed to the ordering facility. We appreciate your assistance in helping Mayo
Medical Laboratories preserve patient confidentiality. Provision of appropriate identifiers will greatly assist
prompt and accurate response to inquiries and reporting.
Critical Values
The Critical Values Policy of the Department of Laboratory Medicine and Pathology (DLMP), Mayo Clinic,
Rochester, Minnesota is described below. These values apply to Mayo Clinic patients as well as the extramural
practice administered through affiliate Mayo Medical Laboratories. Clients should provide Critical Value
contact information to Mayo Laboratory Inquiry to facilitate call-backs. To facilitate this process, a customized
form is available at mayomedicallaboratories.com
Definition of Critical ValueA critical value is defined by Mayo Clinic physicians as a value that represents a
pathophysiological state at such variance with normal (expected values) as to be life-threatening unless
something is done promptly and for which some corrective action could be taken.
Abnormals are Not Considered Critical Values Most laboratory tests have established reference ranges,
which represent results that are typically seen in a group of healthy individuals. While results outside these
reference ranges may be considered abnormal, abnormal results and critical values are not synonymous.
Analytes on the DLMP Critical Values List represent a subgroup of tests that meet the above definition.
Action Taken when a Result is Obtained that Exceeds the Limit Defined by the DLMP Critical Values ListIn
addition to the normal results reporting (eg, fax, interface), Mayo Medical Laboratories staff telephone the
ordering physician or the client-provided contact number within 60 minutes following laboratory release of the
critical test result(s). In the event that contact is not made within the 60-minute period, we continue to telephone
until the designated party is reached and the result is conveyed in compliance and adherence to the CAP.
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Semi-Urgent Results Semi-Urgent Results are defined by Mayo Clinic as those infectious disease-related
results that are needed promptly to avoid potentially serious health consequences for the patient (or in the case
of contagious diseases, potentially serious health consequences to other persons exposed to the patient) if not
acknowledged and/or treated by the physician. While not included on the Critical Values List, this information
is deemed important to patient care in compliance and adherence to the CAP.
To complement Mayo Medical Laboratories normal reporting mechanisms (eg, fax, interface), Mayo Medical
Laboratories staff will telephone results identified as significant microbiology findings to the ordering facility
within 2 hours following laboratory release of the result(s). In the event that contact is not made within the 2-
hour period, we will continue to telephone until the responsible party is reached and the result is conveyed. In
addition, in most instances, you will see the comment SIGNIFICANT RESULT appear on the final report.
For information regarding the Mayo Clinic Critical Value List, contact Mayo Medical Laboratories at
800-533-1710 or 507-266-5700 or visit mayomedicallaboratories.com.
Disclosures of Results
Under federal regulations, we are only authorized to release results to ordering physicians or other health care
providers responsible for the individual patients care. Third parties requesting results, including requests
directly from the patient, are directed to the ordering facility.
Fee Changes
Fees are subject to change without notification and complete pricing per accession number is available once
accession number is final. Specific client fees are available by calling Mayo Laboratory Inquiry at 800-533-
1710 or 507-266-5700 or by visiting mayomedicallaboratories.com.
A core principle at Mayo Medical Laboratories is the continuous improvement of all processes and services that
support the care of patients. Our continuous improvement process focuses on meeting the needs of you, our
client, to help you serve your patients.
Framework for Quality is composed of 12 Quality System Essentials. The policies, processes, and
procedures associated with the Quality System Essentials can be applied to all operations in the path of
workflow (eg, pre-analytical, analytical, and post-analytical). Performance is measured through constant
monitoring of activities in the path of workflow and comparing performance through benchmarking internal and
external quality indicators and proficiency testing.
Data generated by quality indicators drives process improvement initiatives to seek resolutions to system-wide
problems. Mayo Medical Laboratories utilizes Failure Modes and Effects Analysis (FMEA), Plan Do Study
Act (PDSA), LEAN, Root Cause Analysis, and Six Sigma quality improvement tools to determine
appropriate remedial, corrective, and preventive actions.
Quality IndicatorsMayo Medical Laboratories produces hundreds of Key Performance Indicators for our
business and operational areas, and we review them regularly to ensure that we continue to maintain our high
standards. A sampling of these metrics includes:
Pre-analytic performance indicators
o Lost specimens*
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oOn-time delivery
oSpecial handling calls
oSpecimen acceptability*
oSpecimen identification*
oIncoming defects*
Analytic performance indicators
o Proficiency testing
o Test reliability
o Turnaround (analytic) times
o Quantity-not-sufficient (QNS) specimens*
Post-analytic performance indicators
o Revised reports*
o Critical value reports*
Operational performance indicators
o Incoming call resolution*
o Incoming call abandon rate
o Call completion rate
o Call in-queue monitoring
o Customer complaints
o Customer satisfaction surveys
The system provides a planned, systematic program for defining, implementing, monitoring, and evaluating
our services.
HIPAA Compliance
Mayo Medical Laboratories is fully committed to compliance with all privacy, security, and electronic
transaction code requirements of the Health Insurance Portability and Accountability Act of 1996 (HIPAA). All
services provided by Mayo Medical Laboratories that involve joint efforts will be done in a manner which
enables our clients to be HIPAA and the College of American Pathologists (CAP) compliant.
Infectious Material
The Centers for Disease Control (CDC) in its regulations of July 21, 1980, has listed organisms/diseases for
which special packaging and labeling must be applied. Required special containers and packaging instructions
can be obtained from us by using the Request for Supplies form or by ordering from the online Supply
Catalog at mayomedicallaboratories.com/customer-service/supplies/index.php.
Shipping regulations require that infectious substances affecting humans be shipped in a special manner. See
Infectious Material. A copy of the regulations can be requested from the International Air Transport
Association (IATA); they may be contacted by phone at 514-390-6770 or faxed at 514-874-2660.
On occasion, we forward a specimen to an outside reference laboratory. The laws of the state where the
reference laboratory is located may require written informed consent for certain tests. Mayo Medical
Laboratories will request that ordering physician pursue and provide such consent. Test results may be delayed
or denied if consent is not provided.
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Non-Biologic Specimens
Due to the inherent exposure risk of non-biologic specimens, their containers, and the implied relationship to
criminal, forensic, and medico-legal cases, Mayo Medical Laboratories does not accept nor refer non-biologic
specimen types. Example specimens include: unknown solids and liquids in the forms of pills, powder,
intravenous fluids, or syringe contents.
Mayo Medical Laboratories uses multiple patient identifiers to verify the correct patient is matched with the
correct specimen and the correct order for the testing services. As a specimen is received at Mayo Medical
Laboratories, the client number, patient name, and patient age date of birth are verified by comparing the labels
on the specimen tube or container with the electronic order and any paperwork (batch sheet or form) which may
accompany the specimen to be tested. When discrepancies are identified, the Mayo Laboratory call center will
call the client to verify discrepant information to assure Mayo Medical Laboratories is performing the correct
testing for the correct patient. When insufficient or inconsistent identification is submitted, Mayo Medical
Laboratories will recommend that a new specimen be obtained, if feasible.
In addition, Anatomic Pathology consultation services require the Client Pathology Report. The pathology
report is used to match the patient name, patient age and/or date of birth, and pathology case number.
Since tissue blocks and slides have insufficient space to print the patient name on the block, the pathology
report provides Mayo Medical Laboratories another mechanism to confirm the patient identification with the
client order and labels on tissue blocks and slides.
Parallel Testing
Parallel testing may be appropriate in some cases to re-establish patient baseline results when converting to a
new methodology at Mayo Medical Laboratories. Contact your Regional Manager at 800-533-1710 or 507-266-
5700 for further information.
Proficiency Testing
We are a College of American Pathologists (CAP)-accredited, CLIA-licensed facility that voluntarily
participates in many diverse external and internal proficiency testing programs. It is Mayo Medical
Laboratories expectation that clients utilizing our services will adhere to CLIA requirements for proficiency
testing (42 CFR 493.801), including a prohibition on discussion about samples or results and sharing of
proficiency testing materials with Mayo Medical Laboratories during the active survey period. Referring of
specimens is acceptable for comparison purposes when outside of the active survey period or when an approved
proficiency testing program is not available for a given analyte.
Mayo Medical Laboratories proficiency testing includes participation in programs conducted by CAP and the
Centers for Disease Control and Prevention (CDC) along with independent state, national, and international
programs. Our participation includes:
American Association of Bioanalysts (AAB)
AABB (Formerly American Association of Blood Banks) Immunohematology Reference
Laboratory
The Binding Site
Centers for Disease Control and Lipid Standardization Program
Centers for Disease Control and Prevention (CDC)
College of American Pathologists (CAP) Surveys
Cystic Fibrosis European Network
EMQN EQA Scheme
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We conduct internal assessments and comparability studies to ensure the accuracy and reliability of patient
testing when an approved proficiency-testing program is not available or additional quality monitoring is
desired. We comply with the regulations set forth in Clinical Laboratory Improvement Amendments (CLIA-88),
the Occupational Safety and Health Administration (OSHA), or the Centers for Medicare & Medicaid Services
(CMS).
It is Mayo Medical Laboratories expectation that clients utilizing our services will adhere to CLIA
requirements for proficiency testing including a prohibition on discussion about samples or results and sharing
of proficiency testing materials with Mayo Medical Laboratories during the active survey period. Referring of
specimens is acceptable for comparison purposes when outside of the active survey period or when an approved
proficiency-testing program is not available for a given analyte.
Radioactive Specimens
Specimens from patients receiving radioactive tracers or material should be labeled as such. All incoming
shipment arriving at Mayo Medical Laboratories are routed through a detection process in receiving to
determine if the samples have any levels of radioactivity. If radioactive levels are detected, the samples are
handled via an internal process that assures we do not impact patient care and the safety of our respective staff.
This radioactivity may invalidate the results of radioimmunoassays (RIA).
Record Retention
Mayo Medical Laboratories retains all test requisitions and patient test results at a minimum for the retention
period required to comply with and adhere to the CAP. A copy of the original report can be reconstructed
including reference ranges, interpretive comments, flags, and footnotes with the source system as the
Department of Laboratory Medicines laboratory information system.
Reflex Testing
Mayo Medical Laboratories identifies tests that reflex when medically appropriate. In many cases, Mayo
Medical Laboratories offers components of reflex tests individually as well as together. Clients should
familiarize themselves with the test offerings and make a decision whether to order a reflex test or an individual
component. Clients, who order a reflex test, can request to receive an Additional Testing Notification Report
which indicates the additional testing that has been performed. This report will be faxed to the client. Clients
who wish to receive the Additional Testing Notification Report should contact their Regional Manager or
Regional Service Representative.
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Reportable Disease
Mayo Medical Laboratories, in compliance with and adherence to the College of American Pathologists (CAP)
Laboratory General Checklist (CAP GEN. 20373) strives to comply with laboratory reporting requirements for
each state health department regarding reportable disease conditions. We report by mail, fax, and/or
electronically, depending upon the specific state health department regulations. Clients shall be responsible for
compliance with any state specific statutes concerning reportable conditions, including, but not limited to, birth
defects registries or chromosomal abnormality registries. This may also include providing patient
address/demographic information. Mayo Medical Laboratories reporting does not replace the client/physician
responsibility to report as per specific state statues.
When necessary to the performance of a test, the ordering physicians name and phone number are
requested as part of Specimen Required. This information is needed to allow our physicians to make
timely consultations or seek clarification of requested services. If this information is not provided at the time
of specimen receipt, we will call you to obtain the information. By providing this information up front,
delays in patient care are avoided.
In some situations, additional information from ordering physician is necessary to clarify or interpret a test
result. At that time, Mayo Medical Laboratories will request physicians name and phone number so that 1
of our staff can consult with the physician.
We appreciate your rapid assistance in supplying us with the ordering physicians name and phone number
when we are required to call. Working together, we can provide your patients with the highest quality testing
services in the shortest possible time.
Special Handling
Mayo Medical Laboratories serves as a reference laboratory for clients around the country and world. Our test
information, including days and time assays are performed as well as analytic turnaround time, is included
under each test listing in the Test Catalog on mayomedicallaboratories.com. Unique circumstances may arise
with a patient resulting in a physician request that the specimen or results receive special handling. There are
several options available. These options can only be initiated by contacting Mayo Laboratory Inquiry at
800-533-1710 and providing patient demographic information.
Hold: If you would like to send us a specimen and hold that specimen for testing pending initial test
results performed at your facility, please call Mayo Laboratory Inquiry. We will initiate a hold and
stabilize the specimen until we hear from you.
Expedite: If you would like us to expedite the specimen to the performing laboratory, you can call Mayo
Laboratory Inquiry and request that your specimen be expedited. Once the shipment is received in our
receiving area, we will deliver the specimen to the performing laboratory for the next scheduled analytic
run. We will not set up a special run to accommodate an expedite request.
STAT: In rare circumstances, STAT testing from the reference laboratory may be required for patients
who need immediate treatment. These cases typically necessitate a special analytic run to turn results
around as quickly as possible. To arrange STAT testing, please have your pathologist, physician, or
laboratory director call Mayo Laboratory Inquiry. He/she will be connected with one of our medical
directors to consult about the patients case. Once mutually agreed upon that there is a need for a STAT,
arrangements will be made to assign resources to run the testing on a STAT basis when the specimen is
received.
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When insufficient or inconsistent identification is submitted, Mayo Medical Laboratories will recommend that a
new specimen be obtained, if feasible.
Specimen Rejection
All tests are unique in their testing requirements. To avoid specimen rejection or delayed turnaround times,
please check the Specimen Required field within each test. You will be notified of rejected or problem
specimens upon receipt.
Please review the following conditions prior to submitting a specimen to Mayo Medical Laboratories:
Full 24 hours for timed urine collection
pH of urine
Lack of hemolysis/lipemia
Specimen type (plasma, serum, whole blood, etc.)
Specimen volume
Patient information requested
Proper identification of patient/specimen
Specimen container (metal-free, separation gel, appropriate preservative, etc.)
Transport medium
Temperature (ambient, frozen, refrigerated)
Specimen Volume
The Specimen Required section of each test includes 2 volumes - preferred volume and minimum volume.
Preferred volume has been established to optimize testing and allows the laboratory to quickly process
specimen containers, present containers to instruments, perform test, and repeat test, if necessary. Many of our
testing processes are fully automated; and as a result, this volume allows hands-free testing and our quickest
turnaround time (TAT). Since patient values are frequently abnormal, repeat testing, dilutions, or other
specimen manipulations often are required to obtain a reliable, reportable result. Our preferred specimen
requirements allow expeditious testing and reporting.
When venipuncture is technically difficult or the patient is at risk of complications from blood loss (eg,
pediatric or intensive care patients), smaller volumes may be necessary. Specimen minimum volume is the
amount required to perform an assay once, including instrument and container dead space.
When patient conditions do not mandate reduced collection volumes, we ask that our clients submit preferred
volume to facilitate rapid, cost-effective, reliable test results. Submitting less than preferred volume may
negatively impact quality of care by slowing TAT, increasing the hands-on personnel time (and therefore cost)
required to perform test.
Mayo Clinic makes every possible effort to successfully test your patients specimen. If you have concerns
about submitting a specimen for testing, please call Mayo Laboratory Inquiry at 800-533-1710 or
507-266-5700. Our staff will discuss the test and specimen you have available. While in some cases specimens
are inadequate for desired test, in other cases, testing can be performed using alternative techniques.
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Supplies
Shipping boxes, specimen vials, special specimen collection containers, and request forms are supplied without
charge. Supplies can be requested using 1 of the following methods: use the online ordering functionality
available at mayomedicallaboratories.com/supplies or call Mayo Laboratory Inquiry at 800-533-1710 or 507-
266-5700.
Test Classifications
Analytical tests offered by Mayo Medical Laboratories are classified according to the FDA labeling of the test
kit or reagents and their usage. Where appropriate, analytical test listings contain a statement regarding these
classifications, test development, and performance characteristics. The classifications include:
Standard Method - This test uses a standard method. Its performance characteristics were
determined by Mayo Clinic in a manner consistent with CLIA requirements.
FDA Approved, Cleared, or Exempt (IVD) - This test has been cleared or approved by the U.S. Food
and Drug Administration (or is exempt from FDA review) and is used per manufacturers instructions.
Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA
requirements.
FDA Modified - This test has been modified from the manufacturer's instructions. Its performance
characteristics were determined by Mayo Clinic in a manner consistent with CLIA requirements.
Analyte Specific Reagent (ASR) - This test was developed using an analyte specific reagent. Its
performance characteristics were determined by Mayo Clinic in a manner consistent with CLIA
requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.
Laboratory Developed Test - This test was developed and its performance characteristics determined
by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or
approved by the U.S. Food and Drug Administration.
Investigational Use Only (IUO) - This test uses a kit labeled by the manufacturer as "investigational
use only" and it is used per manufacturer's instructions. Its performance characteristics were determined
by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or
approved by the U.S. Food and Drug Administration.
Research Use Only (RUO) - This test uses a reagent or kit labeled by the manufacturer as "research use
only" and it is used per manufacturer's instructions. Its performance characteristics were determined by
Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved
by the U.S. Food and Drug Administration.
Each assay utilized at Mayo Clinic, whether developed on site or by others, undergoes an extensive validation
and performance documentation period before the test becomes available for clinical use. Validations follow a
standard protocol that includes:
Accuracy
Precision
Sensitivity
Specificity and interferences
Reportable range
Linearity
Specimen stability
Specimen type comparisons
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Urine preservative studies: stability at ambient, refrigerated, and frozen temperatures and with 7
preservatives; at 1, 3, and 7 days
Comparative evaluation: with current and potential methods
Reference values: using medically evaluated healthy volunteers, male and female, across age groups.
The number of observations required for each test is determined by biostatistic analysis. Unless
otherwise stated, reference values provided by Mayo Medical Laboratories are derived from studies
performed in our laboratories. When reference values are obtained from other sources, the source is
indicated in the Reference Values field.
Workload recording
Limitations of the assay
Clinical utility and interpretation: written by Mayo Clinic medical experts, electronically available
(MayoAccess)
Time-Sensitive Specimens
Please contact Mayo Laboratory Inquiry at 800-533-1710 or 507-266-5700 prior to sending a specimen for
testing of a time-sensitive nature. Relay the following information: facility name, account number, patient name
and/or Mayo Medical Laboratories accession number, shipping information (ie, courier service, FedEx, etc.),
date to be sent, and test to be performed. Place specimen in a separate Mayo Medical Laboratories temperature
appropriate bag. Please write Expedite in large print on outside of bag.
Mayo Medical Laboratories defines TAT as the analytical test time (the time from which a specimen is received
at the testing location to time of result) required. TAT is monitored continuously by each performing laboratory
site within the Mayo Clinic Department of Laboratory Medicine and Pathology. For the most up-to-date
information on TAT for individual tests, please visit us at mayomedicallaboratories.com or contact our Mayo
Laboratory Inquiry at 800-533-1710 or 507-266-5700.
Unlisted Tests
Mayo Medical Laboratories does not list all available test offerings in the paper catalog. New procedures are
developed throughout the year; therefore, some tests are not listed in this catalog. Although we do not usually
accept referred tests of a more routine type, special arrangements may be made to provide your
laboratory with temporary support during times of special need such as sustained instrumentation failure. For
information about unlisted tests, please call Mayo Laboratory Inquiry at 800-533-1710 or 507-266-5700.
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GAAZ Pompe Disease, Full Gene Analysis
35430 Clinical Information: Pompe disease, also known as glycogen storage disease type II, is an
autosomal recessive condition caused by deficiency of acid alpha-glucosidase. Enzyme insufficiency
results in symptoms such as muscle weakness, cardiomyopathy, and respiratory problems. Mutations in
the GAA gene (which encodes acid alpha-glucosidase) are associated with Pompe disease. The diagnosis
of this heterogeneous condition relies on both clinical and laboratory evaluation. Clinically, the condition
is categorized into infantile and late-onset forms based on age of onset, organ involvement, and rate of
progression. The infantile form (or classic Pompe disease) is the most severe form and is characterized by
early onset and rapid progression of cardiac, liver, and muscle problems resulting in death within the first
year. The infantile variant form has a similar age of onset but a milder clinical presentation. On the less
severe end of the spectrum is the late-onset form with childhood, juvenile, or adult onset. The rate of
progression and severity of symptoms is quite variable, particularly in the late-onset forms. The incidence
varies by clinical type and ethnic population; the combined incidence is approximately 1 in 40,000
individuals. Biochemical testing of acid alpha-glucosidase in blood spot specimens or fibroblasts is useful
for individuals with a suspected diagnosis of Pompe disease (GAABS / Acid Alpha-Glucosidase, Blood
Spot). When clinical manifestations and results of that analysis are supportive of a diagnosis of Pompe
disease, mutation analysis of the GAA gene is warranted. Over 250 different mutations have been
identified in this gene including point mutations and large deletions. GAA full gene sequencing provided
by this test will detect 2 mutations in approximately 83% to 93% of individuals with confirmed GAA
enzyme deficiency. Identification of mutations provides confirmation of the diagnosis and allows for
subsequent testing of at risk family members.
Useful For: Confirmation of diagnosis of Pompe disease (as a follow-up to biochemical analyses)
Interpretation: All detected alterations are evaluated according to American College of Medical
Genetics recommendations.(1) Variants are classified based on known, predicted, or possible
pathogenicity and reported with interpretive comments detailing their potential or known significance.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for
standards of interpretation and reporting of sequence variations: revisions 2007. Genet Med
2008;10(4):294-300 2. Kishnani PS, Steiner RD, Bali D, et al: Pompe disease diagnosis and management
guideline. Genet Med 2006 May;8(5):267-288 3. Van der Ploeg AT, Reuser AJJ: Pompe's disease. Lancet
2008;372(9646):1342-1353 4. Kroos M, Pomponio RJ, van Vliet L, et al: Update of the Pompe disease
mutation database with 107 sequence variants and a format for severity rating. Hum Mut
2008;29(6):E13-26 5. Hirschhorn R, Reuser AJJ. Glycogen storage disease type II: (acid maltase)
deficiency. In Online Metabolic and Molecular Bases of Inherited Disease (OMMBID). Edited by CR
Scriver, AL Beaudet, WS Sly, et al: New York, McGraw-Hill, Inc., available at www.ommbid.com
Accessed 3-6-08
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nonregulated 1-alpha hydroxylase in the lesion may have elevated 1,25-dihydroxy vitamin D levels and
hypercalcemia. 1,25-Dihydroxy vitamin D levels are decreased in hypoparathyroidism and in chronic
renal failure. While 1,25-dihydroxy vitamin D is the most potent vitamin D metabolite, levels of the
25-OH forms of vitamin D more accurately reflect the body's vitamin D stores. Consequently, 25HDN /
25-Hydroxyvitamin D2 and D3, Serum is the preferred initial test for assessing vitamin D status.
However, in the presence of renal disease, 1,25-dihydroxy vitamin D levels may be needed to adequately
assess vitamin D status.
Useful For: As a second-order test in the assessment of vitamin D status, especially in patients with
renal disease Investigation of some patients with clinical evidence of vitamin D deficiency (eg, vitamin
D-dependent rickets due to hereditary deficiency of renal 1-alpha hydroxylase or end-organ resistance
to 1,25-dihydroxy vitamin D) Differential diagnosis of hypercalcemia
Interpretation: 1,25-Dihydroxy vitamin D concentrations are low in chronic renal failure and
hypoparathyroidism. 1,25-Dihydroxy vitamin D concentrations are high in sarcoidosis and other
granulomatous diseases, some malignancies, primary hyperparathyroidism, and physiologic
hyperparathyroidism. 1,25-dihydroxy vitamin D concentrations are not a reliable indicator of vitamin D
toxicity; normal (or even low) results may be seen in such cases.
Reference Values:
Males
<16 years: 24-86 pg/mL
> or =16 years: 18-64 pg/mL
Females
<16 years: 24-86 pg/mL
> or =16 years: 18-78 pg/mL
Clinical References: 1. Endres DB, Rude RK: Vitamin D and its metabolites. In Tietz Textbook of
Clinical Chemisty. Third edition. Edited by CA Burtis, ER Ashwood. Philadelphia, WB Saunders
Company, 1999, pp 1417-1423 2. Bringhurst FR, Demay MB, Kronenberg HM: Vitamin D
(calciferols): metabolism of vitamin D. In Williams Textbook of Endocrinology. Ninth edition. Edited
by JD Wilson, DW Foster, HM Kronenberg, PR Larsen. Philadelphia, WB Saunders Company, 1998,
pp 1166-1169
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inhibition in the TxA2 pathway, along with identification of a patients ability to benefit from
antiplatelet therapy, and their associated risk for developing future cardiovascular events.
Useful For: Assessing if a patient will derive benefit from aspirin therapy Determining an
individuals risk of coronary heart disease and stroke Identifying the effectiveness of antiplatelet
therapies
Interpretation: The normal reference range was derived from an in-house normal donor study with
individuals who were self-reported as not taking any aspirin, nonsteroidal anti-inflammatory drugs
(NSAIDs), or other lipid-lowering therapies. Elevated concentrations of urine thromboxane B2 (TxB2)
may indicate an increase in platelet activation and thrombosis resulting from atherosclerotic deposits or
other vascular obstructions and may identify those individuals who may be at increased risk for an
ischemic cardiovascular event. Elevations of TxB2 in patients already receiving antiplatelet therapies
suggest a failure in the suppression of laboratory-assessed platelet function, a continued hypercoagulable
state, and alternative antithrombotic or antiplatelet therapies may be considered. The liquid
chromatography-tandem mass spectrometry method is specific for TxB2 and is not subject to interference
from the other metabolite of thromboxane A2, the 2,3-dinor-TxB2 component.
Reference Values:
> or =18 years: 0-2,211 pg/mg creatinine
Reference values have not been established for patients who are <18 years of age.
Reference intervals apply to patients not taking agents known to influence platelet function (aspirin or
other nonsteroidal anti-inflammatory drugs, thienopyridines, etc). Healthy individuals taking aspirin
typically have 11-dehydro-thromboxane B2 concentrations below 500 pg/mg creatinine using this
method.
Clinical References: 1. Patrono C, Garcia Rodriguez LA, Landolfi R, Baigent C: Low-dose aspirin
for the prevention of atherothrombosis. N Engl J Med 2005;353:2373-2383 2. Gluckman TJ, McLean RC,
Schulman SP, et al: Effects of aspirin responsiveness and platelet reactivity on early vein graft thrombosis
after coronary artery bypass graft surgery. J Am Coll Cardiol 2011; 57:1069-1077 3. Pignone M,
Williams CD: Aspirin for primary prevention of cardiovascular disease in diabetes mellitus. Nature
2010;6:619-628 4. Eikelboom JW, Hankey GJ, Thom J, et al: Incomplete inhibition of thromboxane
biosynthesis by acetylsalicylic acid: determinants and effect on cardiovascular risk. Circulation
2008;118:1705-1712 5. Armstrong PC, Truss NJ, Ali FY, et al: Aspirin and the in vitro linear relationship
between thromboxane A2-mediated platelet aggregation and platelet production of thromboxane A2. J
Thromb Haemost 2008;6:1933-1943
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cases), and those with the extremely rare StAR (steroidogenic acute regulatory protein) or 20,22
desmolase deficiencies, might also suffer mineral corticoid deficiency, as the enzyme blocks in these
disorders are proximal to potent mineral corticoids. These patients might suffer salt-wasting crises in
infancy. By contrast, patients with the second most common form of CAH, 11-hydroxylase deficiency
(<5% of cases), are normotensive or hypertensive, as the block affects either CYP11B1 or CYP11B2, but
rarely both, thus ensuring that at least corticosterone is still produced. In addition, patients with all forms
of CAH might suffer the effects of substrate accumulation proximal to the enzyme block. In the 3 most
common forms of CAH, the accumulating precursors spill over into the sex steroid pathway, resulting in
virilization of females or, in milder cases, in hirsutism, polycystic ovarian syndrome, or infertility, as well
as in possible premature adrenarche and pubarche in both genders. Measurement of the various precursors
of mature mineral corticoids and glucocorticoids, in concert with the determination of sex steroid
concentrations, allows diagnosis of CAH and its precise type, and serves as an aid in monitoring steroid
replacement therapy and other therapeutic interventions. Measurement of 11-deoxycorticosterone and its
glucocorticoid pendant, 11-deoxycortisol (also known as compound S), is aimed at diagnosing:
-CYP11B1 deficiency (associated with cortisol deficiency) -The rarer CYP11B2 deficiency (no cortisol
deficiency) -The yet less common glucocorticoid-responsive hyperaldosteronism (where expression of the
gene CYP11B2 is driven by the CYP11B1 promoter, thus making it responsive to adrenocorticotrophic
hormone: ACTH rather than renin) For other forms of CAH, the following tests might be relevant:
-11-Hydroxylase deficiency: - DOC / 11-Deoxycortisol, Serum - CORTC / Corticosterone, Serum -
HYD18 / Hydroxycorticosterone, 18 - PRA / Renin Activity, Plasma - ALDS / Aldosterone, Serum
-3-Beta-steroid-dehydrogenase deficiency: - 17PRN / Pregnenolone and 17-Hydroxypregnenolone
-17-Hydroxylase deficiency or 17-lyase deficiency (CYP17A1 has both activities): - PREGN /
Pregnenolone, Serum - 17OHP / 17-Hydroxypregnenolone, Serum - PGSN / Progesterone, Serum -
OHPG / 17-Hydroxyprogesterone, Serum - DHEA / Dehydroepiandrosterone (DHEA), Serum - ANST /
Androstenedione, Serum Cortisol should be measured in all cases of suspected CAH. In the diagnosis of
suspected 11-hydroxylae deficiency and glucocorticoid-responsive hyperaldosteronism, this test should be
used in conjunction with measurements of 11-deoxycortisol, corticosterone, 18-hydroxycorticosterone,
cortisol, renin, and aldosterone.
Useful For: Diagnosis of suspected 11-hydroxylase deficiency, including the differential diagnosis of
11 beta-hydroxylase 1 (CYP11B1) versus 11 beta-hydroxylase 2 (CYP11B2) deficiency, and in the
diagnosis of glucocorticoid-responsive hyperaldosteronism Evaluating congenital adrenal hyperplasia
newborn screen-positive children, when elevations of 17-hydroxyprogesterone are only moderate,
suggesting possible 11-hydroxylase deficiency
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substantially elevated. Conversely, if the deficit affects aldosterone synthase function primarily,
18-hydroxycorticosterone concentrations will be very high. Expression of the CYP11B2 gene is
normally regulated by renin and not ACTH. In glucocorticoid-responsive hyperaldosteronism, the
ACTH-responsive promoter of CYP11B1 exerts aberrant control over CYP11B2 gene expression.
Consequently, corticosterone, 18-hydroxycorticosterone, and aldosterone are significantly elevated in
these patients and their levels follow a diurnal pattern, governed by the rhythm of ACTH secretion. In
addition, the high levels of CYP11B2 lead to 18-hydroxylation of 11-deoxycortisol (an event that is
ordinarily rare, as CYP11B1, which has much greater activity in 11-deoxycortisol conversion than
CYP11B2, lacks 18-hydroxylation activity). Consequently, significant levels of 18-hydroxycortisol,
which normally is only present in trace amounts, might be detected in these patients. Ultimate
diagnostic confirmation comes from showing direct responsiveness of mineral corticoid production to
ACTH1-24 injection. Normally, this has little if any effect on corticosterone, 18-hydroxycorticosterone,
and aldosterone levels. This testing may then be further supplemented by showing that mineral corticoid
levels fall after administration of dexamethasone. Sex steroid levels are moderately to significantly
elevated in CYP11B1 deficiency and much less, or minimally, pronounced in CYP11B2 deficiency. Sex
steroid levels in glucocorticoid-responsive hyperaldosteronism are usually normal. Most untreated
patients with 21-hydroxylase deficiency have serum 17-hydroxyprogesterone concentrations well in
excess of 1,000 ng/dL. For the few patients with levels in the range of higher than 630 ng/dL (upper
limit of reference range for newborns) to 2,000 or 3,000 ng/dL, it might be prudent to consider
11-hydroxylase deficiency as an alternative diagnosis. This is particularly true if serum androstenedione
concentrations are also only mildly to modestly elevated, and if the phenotype is not salt wasting but
either simple virilizing (female) or normal (female or male). 11-Hydroxylase deficiency, in particular if
it affects CYP11B1, can be associated with modest elevations in serum 17-hydroxyprogesterone
concentrations. In these cases, testing for CYP11B1 deficiency and CYB11B2 deficiency should be
considered and interpreted as described above. Alternatively, measurement of 21-deoxycortisol might
be useful. This minor pathway metabolite accumulates in CYP21A2 deficiency, as it requires
21-hydroxylaion to be converted to cortisol, but is usually not elevated in CYP11B1 deficiency, since
its synthesis requires via 11-hydroxylation of 17-hydroxyprogesterone.
Reference Values:
< or =18 years: <30 ng/dL
>18 years: <10 ng/dL
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(midnight) and 8 hours later (overnight test), or at baseline and once per day during a 2-day metyrapone
test (4-times a day metyrapone administration over 2 days). Two-day metyrapone testing has been largely
abandoned because of the logistical problems of multiple timed urine and blood collections and the fact
that overnight testing provides very similar results. In either case, the normal response to metyrapone
administration is a fall in serum cortisol levels, triggering a rise in pituitary ACTH secretion, which, in
turn, leads to a rise in 11-deoxycortisol levels due to the ongoing 11-deoxycortisol-to-cortisol conversion
block. In the diagnostic workup of suspected adrenal insufficiency, the results of overnight metyrapone
testing correlate closely with the gold standard of HPA-axis assessment, insulin hypoglycemia testing.
Combining 11-deoxycortisol measurements with ACTH measurements during metyrapone testing further
enhances the performance of the test. Impairment of any component of the HPA-axis results in a
subnormal rise in 11-deoxycortisol levels. By contrast, standard-dose or low-dose ACTH(1-24)
(cosyntropin)-stimulation testing, which forms the backbone for diagnosis of primary adrenal failure
(Addison disease), only assess the ability of the adrenal cells to respond to ACTH stimulation. While this
allows unequivocal diagnosis of primary adrenal failure, in the setting of secondary or tertiary adrenal
insufficiency, metyrapone testing is more sensitive and specific than either standard-dose or low-dose
ACTH(1-24)-stimulation testing. Metyrapone testing is also sometimes employed in the differential
diagnosis of Cushing syndrome. In Cushing disease (pituitary-dependent ACTH overproduction), the
ACTH-hypersecreting pituitary tissue remains responsive to the usual feedback stimuli, just at a higher
"set-point" than in the normal state, resulting in increased ACTH secretion and 11-deoxycortisol
production after metyrapone administration. By contrast, in Cushing syndrome due to primary adrenal
corticosteroid oversecretion or ectopic ACTH secretion, pituitary ACTH production is appropriately shut
down and there is usually no further rise in ACTH and, hence 11-deoxycortisol, after metyrapone
administration. The metyrapone test has similar sensitivity and specificity to the high-dose
dexamethasone suppression test in the differential diagnosis of Cushing disease, but is less widely used
because of the lack of availability of an easy, automated 11-deoxycortisol assay. In recent years, both tests
have been supplanted to some degree by corticotropin-releasing hormone (CRH)-stimulation testing with
petrosal sinus serum ACTH sampling. See Steroid Pathways in Special Instructions.
Useful For: Diagnostic workup of patients with congenital adrenal hyperplasia Part of metyrapone
testing in the workup of suspected secondary or tertiary adrenal insufficiency Part of metyrapone testing
in the differential diagnostic workup of Cushing syndrome
Reference Values:
< or =18 years: <344 ng/dL
>18 years: 10-79 ng/dL
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FDSOX 11-Desoxycortisol (Specific Compound S)
91690 Reference Values:
Age Range
Premature (26-28w) Day 4 110-1376
Premature (31-35w) Day 4 48-579
Newborn Day 3 13-147
31d-11m <10-156
Prepubertal 8:00 AM 20-155
Pubertal Children and
Adults 8:00 AM 12-158
Useful For: Detection of in utero drug exposure up to 5 months before birth Chain of custody is
required whenever the results of testing could be used in a court of law. Its purpose is to protect the rights
of the individual contributing the specimen by demonstrating that it was under the control of personnel
involved with testing the specimen at all times; this control implies that the opportunity for specimen
tampering would be limited. Since the evidence of illicit drug use during pregnancy can be cause for
separating the baby from the mother, a complete chain of custody ensures that the test results are
appropriate for legal proceedings.
Reference Values:
Negative
Positives are reported with a quantitative LC-MS/MS result.
Cutoff concentrations
Tetrahydrocannabinol carboxylic acid (marijuana metabolite) by LC-MS/MS: 10 ng/g
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Clinical References: 1. Huestis MA: Marijuana. In Principles of Forensic Toxicology. Second
edition. Edited by B Levine. Washington DC, AACC Press, 2003 pp 229-264 2. O'Brein CP: Drug
addiction and drug abuse. In Goodman and Gilman's The Pharmacological Basis of Therapeutics. 11th
edition. Edited by LL Burton, JS Lazo, KL Parker. McGraw-Hill Companies Inc, 2006. Available at
URL: www.accessmedicine.com/content.aspx?aID=941547 3. Baselt RC: Tetrahydrocannabinol. In
Disposition of Toxic Drugs and Chemical in Man. Edited by RC Baselt. Foster City, CA, Biomedical
Publications, 2008: pp1513-1518 4. Ostrea EM Jr, Knapop DK, Tannenbaum L, et al: Estimates of
illicit drug use during pregnancy by maternal interview, hair analysis, and meconium analysis. J Pediatr
2001;138:344-348 5. Ostrea EM Jr, Brady MJ, Parks PM, et al: Drug screening of meconium in infants
of drug-dependent mothers: an alternative to urine testing. J Pediatr 1989;115:474-477 6. Ahanya SN,
Lakshmanan J, Morgan BL, Ross MG: Meconium passage in utero: mechanisms, consequences, and
management. Obstet Gynecol Surv 2005;60:45-56
Reference Values:
Negative
Positives are reported with a quantitative LC-MS/MS result.
Cutoff concentrations
Tetrahydrocannabinol carboxylic acid (marijuana metabolite) by LC-MS/MS: 10 ng/g
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2001;138:344-348 5. Ostrea EM Jr, Brady MJ, Parks PM, et al: Drug screening of meconium in infants
of drug-dependent mothers: an alternative to urine testing. J Pediatr 1989;115:474-477 6. Ahanya SN,
Lakshmanan J, Morgan BL, Ross MG: Meconium passage in utero: mechanisms, consequences, and
management. Obstet Gynecol Surv 2005;60:45-56
Useful For: Supporting, in conjunction with other tests, a diagnosis of Creutzfeldt-Jakob disease in
patients with rapidly progressive dementia when other neurodegenerative conditions have been excluded.
Interpretation: A concentration of 14-3-3 protein in cerebrospinal fluid (CSF) of > or =1.5 ng/mL
supports the diagnosis of Creutzfeldt-Jakob disease (CJD) in patients who have been carefully preselected
based on various diagnostic criteria. CSF 14-3-3 measurement is particularly helpful in sporadic CJD,
where it is used as 1 of several diagnostic criteria. Sporadic CJD World Health Organization (WHO)
diagnostic criteria from 1998: 1. Definitive CJD: -Neuropathological diagnosis by standard techniques
AND/OR immunohistochemistry AND/OR Western blot confirmed protease-resistant prion protein
AND/OR presence of scrapie-associated fibrils 2. Probable CJD: -Progressive dementia -At least 2 of the
following symptoms: -Myoclonus, pyramidal/extrapyramidal, visual or cerebellar, akinetic mutism
-Positive electroencephalographs (EEG) (periodic epileptiform discharges) AND/OR positive CSF 14-3-3
protein and <2 years disease duration -No alternate diagnosis 3. Possible CJD: -Progressive dementia -At
least 2 of the following symptoms: -Myoclonus, pyramidal/extrapyramidal, visual or cerebellar, akinetic
mutism -No supportive EEG and <2 years disease duration Recently proposed, but not yet universally
accepted, amendments to these criteria center on including magnetic resonance imaging (MRI)
high-signal abnormalities in caudate nucleus and/or putamen on diffusion-weighted imaging (DWI) or
fluid attenuated inversion recovery (FLAIR) as diagnostic criteria for probable CJD. The USA Center of
Disease Control and Prevention supports these modified WHO criteria as of 2010
(http://www.cdc.gov/ncidod/dvrd/cjd/diagnostic_criteria.html). There is no established role for 14-3-3
measurement in the diagnosis of acquired or inherited CJD.
Reference Values:
Normal: < or =2.0 ng/mL
Elevated: >2.0 ng/mL
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Clinical References: 1. Day IN, Thompson RJ: Levels of immunoreactive aldolase C, creatine
kinase-BB, neuronal and non-neuronal enolase, and 14-3-3 protein in circulating human blood cells.
Clin Chim Acta 1984;136:219-228 2. Collins S, Boyd A, Fletcher A, et al: Creutzfeldt-Jakob disease:
diagnostic utility of 14-3-3 protein immunodetection in cerebrospinal fluid. J Clin Neurosci
2000;7:203-208 3. Preissner CM, Aksamit AJ, Parisi JE, Grebe SK: Development and validation of an
immunochemiluminometric assay for 14-3-3 protein. Clin Chem 2009;55(S6):page A199; abstract
D-149 4. Collins S, Boyd A, Fletcher A, et al: Creutzfeldt-Jakob disease: diagnostic utility of 14-3-3
protein immunodetection in cerebrospinal fluid. Clin Neuroscience 2000;7:203-208 5. Burkhard PR,
Sanchez JC, Landis T, et al: CSF detection of the 14-3-3 protein in unselected patients with dementia.
Neurology 2001;56:1528-1533 6. Aksamit AJ, Preissner CM, Homburger HA: Quantitation of 14-3-3
and neuron-specific enolase proteins in CSF in Creutzfeldt-Jakob disease. J Neurol 2001;57:728-730 7.
Castellani RJ, Colucci M, Xie Z, et al: Sensitivity of 14-3-3 protein test varies in subtypes of sporadic
Creutzfeldt-Jakob disease. Neurology 2004;63:436-442
Useful For: Differentiating between type I and type II deletions in patients with a known deletion of
15q11.1-11.3, causative of Prader-Willi syndrome or Angelman Evaluation of dic(15) marker
chromosomes
Interpretation: Any individual with a normal signal pattern (2 signals) in each metaphase is
considered negative for a deletion in the region tested by this probe (see Cautions). Any patient with a
FISH signal pattern indicating loss of the critical region will be reported as having a deletion of the
region tested by this probe.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Butler MG, Bittel DC, Kibiryeva N, et al: Behavioral differences among
subjects with Prader-Willi syndrome and type I and type II deletion and maternal disomy. Pediatrics
2004 Mar;113(3 pt 1):565-573 2. Varela MC, Kok F, Setian N, et al: Impact of molecular mechanisms,
including deletion size, on Prader-Willi syndrome phenotype: study of 75 patients. Clin Genet 2005
Jan;67(1):45-52 3. Chai JH, Locke DP, Greally JM, et al: Identification of four highly conserved genes
between breakpoint hotspots BP1 and BP2 of the Prader-Willi/Angelman syndromes deletion region
that have undergone evolutionary transposition mediated by flanking duplicons. Am J Hum Genet 2003
Oct;73(4):898-925
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D15F 15q11.2 Duplication, FISH
35253 Clinical Information: Individuals with autism spectrum disorders, individuals with supernumerary
chromosomes suspicious for a chromosome 15 origin, individuals with duplications of 15q11-q13
detected by multiplex ligation-dependent probe amplification (MLPA) or other testing methodologies (to
distinguish between interstitial tandem duplication and supernumerary marker). Cytogenetic abnormalities
at the 15q11-q13 locus are reported in up to 4% of patients with autism spectrum disorders. Duplications
in this chromosome region can occur as an interstitial tandem repeat or as a supernumerary isodicentric
chromosome 15, leading to trisomy or tetrasomy of genes at the 15q11-q13 locus. The majority of
interstitial tandem repeats in this region are not detectable by conventional chromosome analysis but can
be identified by FISH. Supernumerary chromosomes can often be identified by conventional chromosome
analysis but their origin must be confirmed by FISH analysis. Molecular analysis by MLPA can also
detect duplications of chromosome 15q, but FISH analysis is necessary to distinguish between interstitial
tandem duplication and a supernumerary marker. The phenotype associated with these abnormalities
depends largely on the amount of duplicated material, as well as parent of origin. Small dicentric markers
with little 15q material duplicated are often familial and result in a normal phenotype. Larger dicentric 15
markers are usually new mutations and result in mild dysmorphic features, mental retardation, and
behavioral abnormalities consistent with autism. Interstitial tandem duplications are associated with
autistic spectrum disorders when maternally inherited, but paternally inherited duplications are less likely
to cause phenotypic effects.
Useful For: Evaluating patients with autistic spectrum disorders for 15q11.1-11.3 region Confirming
the origin of supernumerary marker chromosomes suspected of being derived from chromosome 15
Resolving the origin when duplication of 15q11.1-11.3 is identified via molecular multiplex
ligation-dependent probe amplification analysis
Interpretation: Specimens with a normal signal pattern in metaphase and interphase cells are
considered negative for this probe. Specimens with a FISH signal pattern indicating duplication of the
critical region (3 signals) will be reported as having a duplication of the region tested by this probe.
Clinical References: 1. Mao R, Jalal SM, Snow K, et al: Characteristics of two cases with
dup(15)(q11.2-q12): one of maternal and one of paternal origin. Genet Med 2000;2:131-135 2. Thomas
JA, Johnson J, Peterson Kraai TL, et al: Genetic and clinical characterization of patients with an
interstitial duplication 15q11-q13, emphasizing behavioral phenotype and response to treatment. Am J
Med Genet 2003;119:111-120 3. Battaglia A: The inv dup(15) or idic(15) syndrome: a clinically
recognizable neurogenetic disorder. Brain Dev 2005;5:365-369 4. Muhle R, Trentacoste S, Rapin I: The
genetics of autism. Pediatrics 2004;113:472-486 5. Dennis NR, Veltman MW, Thompson R, et al:
Clinical findings in 33 subjects with large supernumerary marker(15) chromosomes and 3 subjects with
triplication of 15q11-q13. Am J Med Genet A 2006;140:434-441
Reference Values:
Pediatric Reference Ranges:
Newborns and Infants: 3 days to 1 year: Up to 50 ng/24 hrs
Children: 1 - 8 years: Up to 300 ng/24 hrs
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Adult Reference Ranges:
Male: Up to 2.0 ug/24 hrs.
Female: Up to 4.5 ug/24 hrs.
Useful For: As an ancillary test for congenital adrenal hyperplasia (CAH), particularly in situations
in which a diagnosis of 21-hydroxylase and 11-hydroxylase deficiency have been ruled out Confirming
a diagnosis of 3-beta-hydroxy dehydrogenase (3-beta-HSD) deficiency Analysis for
17-hydroxypregnenolone is also useful as part of a battery of tests to evaluate females with hirsutism or
infertility; both can result from adult-onset CAH.
Interpretation: Diagnosis and differential diagnosis of congenital adrenal hyperplasia (CAH) always
requires the measurement of several steroids. Patients with CAH due to steroid 21-hydroxylase gene
(CYP21A2) mutations usually have very high levels of androstenedione, often 5-fold to 10-fold
elevations. 17-hydroxyprogesterone (17-OHPG) levels are usually even higher, while cortisol levels are
low or undetectable. All 3 analytes should be tested. For the HSD3B2 mutation, cortisol, 17-OHPG and
progesterone levels will be will be decreased; 17-hydroxypregnenolone and pregnenolone and
dehydroepiandrosterone (DHEA) levels will be increased. In the much less common CYP11A1
mutation, androstenedione levels are elevated to a similar extent as in CYP21A2 mutation, and cortisol
is also low, but OHPG is only mildly, if at all, elevated. In the also very rare 17-alpha-hydroxylase
deficiency, androstenedione, all other androgen-precursors (17-alpha-hydroxypregnenolone, OHPG,
dehydroepiandrosterone sulfate), androgens (testosterone, estrone, estradiol), and cortisol are low, while
production of mineral corticoid and its precursors (in particular pregnenolone, 11-dexycorticosterone,
corticosterone, and 18-hydroxycorticosterone) are increased. See Steroid Pathways in Special
Instructions.
Reference Values:
CHILDREN*
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Males
Premature (26-28 weeks): 1,219-9,799 ng/dL
Premature (29-36 weeks): 346-8,911 ng/dL
Full term (1-5 months): 229-3,104 ng/dL
6 months-364 days: 221-1,981 ng/dL
1-2 years: 35-712 ng/dL
3-6 years: <277 ng/dL
7-9 years: <188 ng/dL
10-12 years: <393 ng/dL
13-15 years: 35-465 ng/dL
16-17 years: 32-478 ng/dL
TANNER STAGES
Stage I: <209 ng/dL
Stage II: <356 ng/dL
Stage III: <451 ng/dL
Stage IV-V: 35-478 ng/dL
Females
Premature (26-28 weeks): 1,219-9,799 ng/dL
Premature (29-36 weeks): 346-8,911 ng/dL
Full term (1-5 months): 229-3,104 ng/dL
6 months-364 days: 221-1,981 ng/dL
1-2 years: 35-712 ng/dL
3-6 years: <277 ng/dL
7-9 years: <213 ng/dL
10-12 years: <399 ng/dL
13-15 years: <408 ng/dL
16-17 years: <424 ng/dL
TANNER STAGES
Stage I: <236 ng/dL
Stage II: <368 ng/dL
Stage III: <431 ng/dL
Stage IV-V: <413 ng/dL
ADULTS
Males
> or =18 years: 55-455 ng/dL
Females
> or =18 years: 31-455 ng/dL
*Kushnir MM, Rockwood AL, Roberts WL, et al: Development and performance evaluation of a
tandem mass spectrometry assay for 4 adrenal steroids. Clin Chem 2006;52(8):1559-1567
Useful For: The analysis of 17-hydroxyprogesterone (17-OHPG) is 1 of the 3 analytes along with
cortisol and androstenedione, that constitutes the best screening test for congenital adrenal hyperplasia
(CAH), caused by either 11- or 21-hydroxylase deficiency. Analysis for 17-OHPG is also useful as part
of a battery of tests to evaluate females with hirsutism or infertility; both can result from adult-onset
CAH
Interpretation: Diagnosis and differential diagnosis of congenital adrenal hyperplasia (CAH) always
requires the measurement of several steroids. Patients with CAH due to steroid 21-hydroxylase gene
(CYP21A2) mutations usually have very high levels of androstenedione, often 5- to 10-fold elevations.
17-hydroxyprogesterone (OHPG) levels are usually even higher, while cortisol levels are low or
undetectable. All 3 analytes should be tested. In the much less common CYP11A1 mutation,
androstenedione levels are elevated to a similar extent as in CYP21A2 mutation, and cortisol is also
low, but OHPG is only mildly, if at all, elevated. In the also very rare 17-alpha-hydroxylase deficiency,
androstenedione, all other androgen-precursors (17-alpha-hydroxypregnenolone, OHPG,
dehydroepiandrosterone sulfate), androgens (testosterone, estrone, estradiol), and cortisol are low, while
production of mineral corticoid and its precursors, in particular progesterone, 11-deoxycorticosterone,
and 18-hydroxycorticosterone, are increased. The goal of CAH treatment is normalization of cortisol
levels and ideally also of sex-steroid levels. Traditionally, OHPG and urinary pregnanetriol or total
ketosteroid excretion are measured to guide treatment, but these tests correlate only modestly with
androgen levels. Therefore, androstenedione and testosterone should also be measured and used to
guide treatment modifications. Normal prepubertal levels may be difficult to achieve, but if testosterone
levels are within the reference range, androstenedione levels of up to 100 ng/dL are usually regarded as
acceptable. See Steroid Pathways in Special Instructions.
Reference Values:
Children
Preterm infants
Preterm infants may exceed 630 ng/dL, however, it is uncommon to see levels reach 1,000 ng/dL.
Term infants
0-28 days: <630 ng/dL
Levels fall from newborn (<630 ng/dL) to prepubertal gradually within 6 months.
Prepubertal males: <110 ng/dL
Prepubertal females: <100 ng/dL
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 25
Adults
Males: <220 ng/dL
Females
Follicular: <80 ng/dL
Luteal: <285 ng/dL
Postmenopausal: <51 ng/dL
Note: For pregnancy reference ranges, see: Soldin OP, Guo T, Weiderpass E, et al: Steroid hormone
levels in pregnancy and 1 year postpartum using isotope dilution tandem mass spectrometry. Fertil
Steril 2005 Sept;84(3):701-710
Clinical References: 1. Therrell BL: Newborn screening for congenital adrenal hyperplasia.
Endocrinol Metab Clin North Am 2001;30(1):15-30 2. Bachega TA, Billerbeck AE, Marcondes JA, et al:
Influence of different genotypes on 17-hydroxyprogesterone levels in patients with non-classical
congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Clin Endocrinol 2000;52(5):601-607 3.
Von Schnaken K, Bidlingmaier F, Knorr D: 17-hydroxyprogesterone, androstenedione, and testosterone
in normal children and in prepubertal patients with congenital adrenal hyperplasia. Eur J Pediatr
1980;133(3):259-267 4. Sciarra F, Tosti-Croce C, Toscano V: Androgen-secreting adrenal tumors.
Minerva Ednocrinol 1995;20(1):63-68 5. Collett-Solberg PF: Congenital adrenal hyperplasia: from
genetics and biochemistry to clinical practice, part I. Clin Pediatr 2001;40(1):1-16 6. Soldin OP, Guo T,
Weiderpass E, et al: Steroid hormone levels in pregnancy and 1 year postpartum using isotope dilution
tandem mass spectrometry. Fertil Steril 2005 Sept;84(3):701-710 7. Speiser PW, Azziz R, Baskin LS, et
al: Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: An Endocrine Society
Clinical Practice Guideline. J Clin Endocrinol Metab 2010;95(9):4133-4160 Available at:
jcem.endojournals.org
Useful For: Aids in diagnosing oligodendroglioma tumors and predicting the response of an
oligodendroglioma to therapy May be useful in tumors with a complex "hybrid" morphology requiring
differentiation from pure astrocytomas to support the presence of oligodendroglial differentiation/lineage
Indicated when a diagnosis of oligodendroglioma, both low-grade World Health Organization (WHO,
grade II) and anaplastic (WHO, grade III) is rendered Strongly recommended when a diagnosis of mixed
oligoastrocytomas is rendered
Interpretation: The presence of 1p deletion and combined 1p and 19q deletion supports a diagnosis of
oligodendroglioma may indicate that the patient may respond to chemotherapy and radiation therapy. The
presence of gain of chromosome 19 supports a diagnosis of high-grade astrocytoma (glioblastoma
multiforme). A negative result does not exclude a diagnosis of oligodendroglioma or high-grade
astrocytoma.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 26
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Eckel-Passow JE, Lachance DH, Molinaro AM, et al: Glioma Groups
Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors. N Engl J Med 2015 Jun
25;372(26):2499-2508 2. James CD, Smith JS, Jenkins RB: Genetic and molecular basis of primary
central nervous system tumors. In Cancer in the Nervous System. Edited by VA Levine. New York,
Oxford University Press, 2002, pp 239-251 3. Cairncross JG, Ueki K, Zlatescu MC, et al: Specific
genetic predictors of chemotherapeutic response and survival in patients with anaplastic
oligodendrogliomas. J Natl Cancer Inst 1998 October 7;90(19):1473-1479 4. Ino Y, Zlatescu MC,
Sasaki H, et al: Long survival and therapeutic responses in patients with histologically disparate
high-grade gliomas demonstrating chromosome 1p loss. J Neurosurg 2000 June;92(6):983-990 5. Smith
JS, Tachibana I, Passe SM, et al: PTEN mutation, EGFR amplification, and outcome in patients with
anaplastic astrocytoma and glioblastoma multiforme. J Natl Cancer Inst 2001 August
15;93(16):1246-1256 6. Smith JS, Alderete B, Minn Y, et al: Localization of common deletion regions
on 1p and 19q in human gliomas and their association with histological subtype. Oncogene 1999 July
15;18(28):4144-4152 7. Smith JS, Perry A, Borell TJ, et al: Alterations of chromosome arms 1p and 19q
as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas. J Clin
Oncol 2000 February;18(3):636-645 8. Jenkins RB, Curran W, Scott CB, et al: Pilot evaluation of 1p
and 19q deletions in anaplastic oligodendrogliomas collected by a national cooperative cancer treatment
group. Am J Clin Oncol 2001 October;24(5):506-508 9. Burger PC: What is an oligodendroglioma?
Brain Pathol 2002;12:257-259
Useful For: Establishing a diagnosis of 1p36 deletion syndrome Detecting cryptic rearrangements
involving 1p36.3 that are not demonstrated by conventional
Interpretation: Any individual with a normal signal pattern (2 signals) in each metaphase is
considered negative for a deletion in the region tested by this probe. Any patient with a FISH signal
pattern indicating loss of the critical region will be reported as having a deletion of the region tested by
this probe. This is consistent with a diagnosis of 1p microdeletion syndrome.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Hielstedt HA, Ballif BC, Howard LA, et al: Physical map of 1p36,
placement of breakpoints in monosomy 1p36, and clinical characterization of the syndrome. Am J Hum
Genet 2003;72:1200-1212 2. Heilstedt HA, Ballif BC, Howard LA, et al: Population data suggests that
deletions of 1p36 are a relatively common chromosome abnormality. Clin Genet 2003;64:310-316 3.
Battaglia A: 1p36 Deletion Syndrome. 2008 Feb 1 (Updated 2013 Jun 6). In: Pagon RA, Adam MP,
Ardinger HH, et al, editors. GeneReviews (Internet). Seattle (WA): University of Washington, Seattle;
1993-2014. Available at: http://www.ncbi.nlm.nih.gov/books/NBK1191/ Accessed 12/02/2013
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 27
Secondary erythrocytosis is associated with a number of disorders including chronic lung disease,
chronic increase in carbon monoxide (due to smoking), cyanotic heart disease, high-altitude living, renal
cysts and tumors, hepatoma, and other Epo-secreting tumors. When these common causes of secondary
erythrocytosis are excluded, a heritable cause involving hemoglobin or erythrocyte regulatory
mechanism may be suspected. Unlike PV, hereditary erythrocytosis is not associated with the risk of
clonal evolution and should present with isolated erythrocytosis that has been present since birth. A rare
subset of cases is associated with pheochromocytoma and paraganglioma formation later in life.
Hereditary erythrocytosis may be caused by mutations in one of several genes and inherited in either an
autosomal dominant or autosomal recessive manner. A family history of erythrocytosis would be
expected in these cases, although de novo mutations have also been reported. Genetic mutations causing
hereditary erythrocytosis have been found in genes coding for alpha and beta hemoglobins, hemoglobin
stabilization proteins (eg, 2,3-bisphosphoglycerate mutase: BPGM), the erythropoietin receptor
(EPOR), and oxygen-sensing pathway enzymes (hypoxia-inducible factor: HIF, prolyl hydroxylase
domain: PHD, and von Hippel Lindau: VHL), see table. High-oxygen-affinity hemoglobin variants and
BPGM abnormalities result in a decreased p50 result, whereas those affecting EPOR, HIF, PHD, and
VHL have normal p50 results. The true prevalence of mutations causing hereditary erythrocytosis is
unknown. Table. Erythrocytosis Testing Gene Inheritance Serum Epo p50 JAK2 V617F Acquired
Decreased Normal JAK2 exon 12 Acquired Decreased Normal EPOR Dominant Decreased to normal
level Normal PHD2/EGLN1 Dominant Normal level Normal BPGM Recessive Normal level Decreased
Beta Globin Dominant Normal level to increased Decreased Alpha Globin Dominant Normal level to
increased Decreased HIF2A/EPAS1 Dominant Normal level to increased Normal VHL Recessive
Markedly Increased Normal
Interpretation: An interpretive report will be provided and will include specimen information, assay
information, and whether the specimen was positive for any mutations in the gene. If positive, the
mutation will be correlated with clinical significance, if known.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Petousi N, Copley RR, Lappin TR, et al: Erythrocytosis associated with a
novel missense mutation in the BPGM gene. Haematologica 2014 Oct;99:e201-e204 2. Hoyer JD, Allen
SL, Beutler E, et al: Erythrocytosis due to bisphosphoglycerate mutase deficiency with concurrent
glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. Am J Hematol 2004;75(4):205-208 3. Rosa R,
Prehu MO, Beuzard Y, Rosa J: The first case of a complete deficiency of diphosphoglycerate mutase in
human erythrocytes. J Clin Invest 1978;62(5):907-915
Useful For: Screening for mast cell activation disorders including systemic mastocytosis
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Interpretation: Elevated urine 2,3-dinor-11beta-prostaglandin F2 alpha is consistent with systemic
mastocytosis.
Reference Values:
<5,205 pg/mg creatinine
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relevant: -11-Hydroxylase deficiency: - DOC / 11-Deoxycortisol, Serum - CORTC / Corticosterone,
Serum - PRA / Renin Activity, Plasma - ALDS / Aldosterone, Serum -3-Beta-steroid-dehydrogenase
deficiency: - 17PRN / Pregnenolone and 17-Hydroxypregnenolone -17-Hydroxylase deficiency or
17-lyase deficiency (CYP17A1 has both activities): - PREGN / Pregnenolone, Serum - 17OHP /
17-Hydroxypregnenolone, Serum - PGSN / Progesterone, Serum - OHPG / 17-Hydroxyprogesterone,
Serum - DHEA_ / Dehydroepiandrosterone (DHEA), Serum - ANST / Androstenedione, Serum Cortisol
should be measured in all cases of suspected CAH. It has been suggested that in the pubertal patient
with 21-hydroxylase deficiency, 21-deoxycortisol may be useful and better then
17-hydroxyprogesterone for therapeutic decisions.
Reference Values:
<5.0 ng/dL
Reference values apply to all ages.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 30
hyperplasia. Eur J Pediatr 1980;133(3):259-267 2. Therrell BL: Newborn screening for congenital adrenal
hyperplasia. Endocrinol Metab Clin North Am 2001;30(1):15-30 3. Collett-Solberg PF: Congenital
adrenal hyperplasia: from genetics and biochemistry to clinical practice, part I. Clin Pediatr 2001;40:1-16
4. Forest MG: Recent advances in the diagnosis and management of congenital adrenal hyperplasia due to
21-hydroxylase deficiency. Hum Reprod Update 2004;10:469-485 5. Tonetto-Fernandes V,
Lemos-Marini SH, Kuperman H, et al: Serum 21-deoxycortisol, 17-hydroxyprogesterone, and
11-deoxycortisol in classic congenital adrenal hyperplasia: clinical and hormonal correlations and
identification of patients with 11beta-hydroxylase deficiency among a large group with alleged
21-hydroxylase deficiency. J Clin Endocrinol Metab 2006;91:2179-2184
Useful For: Investigation of adrenal insufficiency Aid in the detection of those at risk of developing
autoimmune adrenal failure in the future
Interpretation: Positive results (> or =1 U/mL) indicate the presence of adrenal autoantibodies
consistent with Addison disease.
Reference Values:
<1 U/mL
Reference values apply to all ages.
Clinical References: 1. Husebye ES, Allolio B, Arlt W, et al: Consensus statement on the
diagnosis, treatment and follow-up of patients with primary adrenal insufficiency. J Intern Med 2014
Feb;275(2):104-115 2. Tanaka H, Perez M, Powell M, et al: Steroid 21 hydroxylase autoantibodies:
measurements with a new immunoprecipitation assay. J Clin Endocrinol Metab 1997;82:1440-1446
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 31
Screening, Blood Spot), or retesting after several weeks, is required for most positive screens because of
the high false-positive rates of the immunoassays (due to physiological elevations of
17-hydroxyprogesterone in premature babies and immunoassay cross-reactivity with other steroids). In
a small percentage of cases, additional testing will fail to provide a definitive diagnosis. In addition,
screening strategies can miss many non-classical cases, which may present later in childhood or
adolescence and require more extensive steroid hormone profiling, including testing before and after
adrenal stimulation with adrenocorticotropic hormone (ACTH)-1-24. For these reasons, genetic
diagnosis plays an important ancillary role in both classical and non-classical cases. In addition, the
high carrier frequency (approximately 1 in 50) for CYP21A2 mutations makes genetic diagnosis
important for genetic counseling. Genetic testing can also play a role in prenatal diagnosis of
21-hydroxylase deficiency. However, accurate genetic diagnosis continues to be a challenge because
most of the mutations arise from recombination events between CYP21A2 and its highly homologous
pseudogene, CYP21A1P (transcriptionally inactive). In particular, partial or complex rearrangements
(with or without accompanying gene duplication events), which lead to reciprocal exchanges between
gene and pseudogene, can present severe diagnostic challenges. Comprehensive genetic testing
strategies must therefore allow accurate assessment of most, or all, known rearrangements and
mutations, as well as unequivocal determination of whether the observed changes are located within a
potentially transcriptionally active genetic segment. Testing of additional family members is often
needed for clarification of genetic test results.
Useful For: Carrier screening and diagnosis of 21-hydroxylase deficient congenital adrenal hyperplasia
(CAH) in individuals with a personal or family history of 21-hydroxylase deficiency, or as follow-up to
positive CAH newborn screens and/or measurement of basal and adrenocorticotropic hormone- 1-24
stimulated 17-hydroxyprogesterone, androstenedione, and other adrenal steroid levels May be used to
identify CYP21A2 mutations in individuals with a suspected diagnosis of 21-hydroxylase deficient CAH
when a common mutation panel is negative or only identifies 1 mutation. In prenatal cases of ambiguous
genitalia detected by ultrasound, particularly when the fetus is confirmed XX female by chromosome
analysis. This test code should also be used for known/familial variant analysis for CYP21A2. Due to the
complexity of the CYP21A2 locus, site specific testing for known/familial variants is not offered for this
gene.
Interpretation: All detected alterations will be evaluated according to American College of Medical
Genetics and Genomics (ACMG) recommendations. Variants will be classified based on known,
predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or
known significance.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for
standards for interpretation and reporting of sequence variations: Revisions 2007. Genet Med
2008:10(4):294-300 2. Collett-Solberg PF: Congenital adrenal hyperplasias: from clinical genetics and
biochemistry to clinical practice, part I. Clin Pediatr 2001;40:1-16 3. Mercke DP, Bornstein SR, Avila
NA, Chrousos GP: NIH conference: future directions in the study and management of congenital adrenal
hyperplasia due to 21-hydroxylase deficiency. Ann Intern Med 2002;136:320-334 4. Speiser PW, White
PC: Medical progress: congenital adrenal hyperplasia. N Engl J Med 2003;349:776-788
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 32
Useful For: Establishing a diagnosis of 22q deletion/duplication syndromes Detecting cryptic
rearrangements involving 22q11.2 or 22q11.3 that are not demonstrated by conventional chromosome
studies
Interpretation: Any individual with a normal signal pattern in each metaphase is considered
negative for this probe. Any patient with a FISH signal pattern indicating loss of the critical region (1
signal) will be reported as having a deletion of the region tested by this probe. This is consistent with a
diagnosis of 22q deletion syndrome. Any patient with a FISH signal pattern indicating duplication of the
critical region (3 signals) will be reported as having a duplication of the region tested by this probe. This
is consistent with a diagnosis 22q duplication syndrome.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Ensenauer RE, Adeyinka A, Flynn HC, et al: Microduplication 22q11.2 an
emerging syndrome: clinical, cytogenetic and molecular analysis of thirteen patients. Am J Hum Genet
2003;73:1027-1040 2. Yobb TM, Sommerville MJ, Willatt L, et al: Microduplication and triplication of
22q11.2: a highly variable syndrome. Am J Hum Genet 2005;76:865-876 3. Bassett AS, Chow EWC,
Husted J, et al: Clinical features of 78 adults with 22q11 deletion syndrome. Am J Med Genet
2005;138A:307-313 4. Manji A, Roberson JR, Wiktor A, et al: Prenatal diagnosis of 22q11.2 deletion
when ultrasound examination reveals a heart defect. Genet Med 2001;3:65-66 5. McDonald-McGinn
DM, Emanuel BS, Zackai EH: 22q11.2 Deletion Syndrome. GeneReviews, Accessed 05/22/2013,
Available at www.ncbi.nlm.nih.gov/books/NBK1523/
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 33
vitamin D. When it occurs, it can result in severe hypercalcemia and hyperphosphatemia.
Useful For: Diagnosis of vitamin D deficiency Differential diagnosis of causes of rickets and
osteomalacia Monitoring vitamin D replacement therapy Diagnosis of hypervitaminosis D
Interpretation: Based on animal studies and large human epidemiological studies, 25-hydroxyvitamin
D2 and D3 (25-OH-VitD) <25 ng/mL are associated with an increased risk of secondary
hyperparathyroidism, reduced bone mineral density, and fractures, particularly in the elderly. Intervention
studies support this clinical cutoff, showing a reduction of fracture risk with 25-OH-VitD replacement.
Levels <10 ng/mL may be associated with more severe abnormalities and can lead to inadequate
mineralization of newly formed osteoid, resulting in rickets in children and osteomalacia in adults. In
these individuals, serum calcium levels may be marginally low, and parathyroid hormone (PTH) and
serum alkaline phosphatase are usually elevated. Definitive diagnosis rests on the typical radiographic
findings or bone biopsy/histomorphometry. Baseline biochemical work-up of suspected cases of rickets
and osteomalacia should include measurement of serum calcium, phosphorus, PTH, and 25-OH-VitD. In
patients where testing is not completely consistent with the suspected diagnosis, in particular if serum
25-OH-VitD levels are >10 ng/mL, an alternative cause for impaired mineralization should be considered.
Possible differential diagnosis includes: partly treated vitamin D deficiency, extremely poor calcium
intake, vitamin D resistant rickets, renal failure, renal tubular mineral loss with or without renal tubular
acidosis, hypophosphatemic disorders (eg, X-linked or autosomal dominant hypophosphatemic rickets),
congenital hypoparathyroidism, activating calcium sensing receptor mutations, and osteopetrosis.
Measurement of serum urea, creatinine, magnesium, and 1,25-OH-VitD is recommended as a minimal
additional work-up for these patients. 25-OH-VitD replacement in the United States typically consists of
VitD2. Lack of clinical improvement and no reduction in PTH or alkaline phosphatase may indicate
patient noncompliance, malabsorption, resistance to 25-OH-VitD, or additional factors contributing to the
clinical disease. Measurement of serum 25-OH-VitD levels can assist in further evaluation, in particular
as the liquid chromatography-tandem mass spectrometry methodology allows separate measurement of
25-OH-VitD3 and of 25-OH-VitD2, which is derived entirely from dietary sources or supplements.
Patients who present with hypercalcemia, hyperphosphatemia, and low PTH may suffer either from
ectopic, unregulated conversion of 25-OH-VitD to 1,25-OH-VitD, as can occur in granulomatous
diseases, particular sarcoid, or from nutritionally-induced hypervitaminosis D. Serum 1,25-OH-VitD
levels will be high in both groups, but only patients with hypervitaminosis D will have serum
25-OH-VitD concentrations of >80 ng/mL, typically >150 ng/mL.
Reference Values:
TOTAL 25-HYDROXYVITAMIN D2 AND D3 (25-OH-VitD)
<10 ng/mL (severe deficiency)*
10-19 ng/mL (mild to moderate deficiency)**
20-50 ng/mL (optimum levels)***
51-80 ng/mL (increased risk of hypercalciuria)****
>80 ng/mL (toxicity possible)*****
*Could be associated with osteomalacia or rickets
**May be associated with increased risk of osteoporosis or secondary hyperparathyroidism
***Optimum levels in the healthy population; patients with bone disease may benefit from higher levels
within this range
****Sustained levels >50 ng/mL 25OH-VitD along with prolonged calcium supplementation may lead
to hypercalciuria and decreased renal function
****80 ng/mL is the lowest reported level associated with toxicity in patients without primary
hyperparathyroidism who have normal renal function. Most patients with toxicity have levels >150
ng/mL. Patients with renal failure can have very high 25-OH-VitD levels without any signs of toxicity, as
renal conversion to the active hormone 1,25-OH-VitD is impaired or absent.
These reference ranges represent clinical decision values, based on the 2011 Institute of Medicine report,
that apply to males and females of all ages, rather than population-based reference values. Population
reference ranges for 25-OH-VitD vary widely depending on ethnic background, age, geographic location
of the studied populations, and the sampling season. Population-based ranges correlate poorly with serum
25-OH-VitD concentrations that are associated with biologically and clinically relevant vitamin D effects
and are therefore of limited clinical value.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 34
Clinical References: 1. Jones G, Strugnell SA, DeLuca HF: Current understanding of the
molecular actions of vitamin D. Physiol Rev 1998 Oct;78(4):1193-1231 2. Miller WL, Portale AA:
Genetic causes of rickets. Curr Opin Pediatr 1999 Aug;11(4):333-339 3. Vieth R: Vitamin D
supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr 1999
May;69(5):842-856 4. Vieth R, Ladak Y, Walfish PG: Age-related changes in the 25-hydroxyvitamin D
versus parathyroid hormone relationship suggest a different reason why older adults require more
vitamin D. J Clin Endocrinol Metab 2003 Jan;88(1):185-191 5. Wharton B, Bishop N: Rickets. Lancet
2003 Oct 25;362(9393):1389-1400 6. Institute of Medicine (US) Committee to Review Dietary
Reference Intakes for Vitamin D and Calcium; Edited by AC Ross, CL Taylor, AL Yaktine, HB Del
Valle. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC. National Academies
Press (US), 2011 Available from: http://www.ncbi.nlm.nih.gov/books/NBK56070
F5NUL 5'Nucleotidase
57285 Useful For:
Reference Values:
0 - 15 U/L
Useful For: Direct mutation analysis for the MTHFR A1298C mutation should be reserved for
patients with coronary artery disease, acute myocardial infarction, peripheral vascular artery disease,
stroke, or venous thromboembolism, who have increased basal homocysteine levels or an abnormal
methionine-load test.
Interpretation: The interpretive report will include specimen information, assay information,
background information, and conclusions based on the test results (negative, heterozygous MTHFR
A1298C, homozygous MTHFR A1298C).
Reference Values:
Negative
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 35
Clinical References: 1. Rees MM, Rodgers GM: Homocysteinemia: association of a metabolic
disorder with vascular disease and thrombosis. Thromb Res 1993;71:337-359 2. Frosst P, Blom HF,
Goyette P, et al: A candidate gene risk factor for vascular disease: a common mutation in
methylenetetrahydrofolate reductase. Nature Genet 1995;10:111-113 3. Deloughery TG, Evans A,
Sadeghi A, et al: Common mutation in methylenetetrahydrofolate reductase: correlation with
homocysteine metabolism and late-onset vascular disease. Circulation 1996;94:3074-3078 4. Henrik Z,
Antonio C, Armando D, et al: No association between the MTHFR A1298C and transcobalamin C776G
genetic polymorphisms and hyperhomocysteinemia in thrombotic disease. Thromb Res 2002;108:127-131
5. Heit JA: Thrombophilia: clinical and laboratory assessment and management. In Consultative
Hemostasis and Thrombosis. Fourth edition. Edited by CS Kitchens, BM Alving, CM Kessler
Useful For: Direct mutation analysis for the MTHFR C677T and/or A1298C mutations should be
reserved for patients with coronary artery disease, acute myocardial infarction, peripheral vascular artery
disease, stroke, or venous thromboembolism who have increased basal homocysteine levels or an
abnormal methionine-load test.
Interpretation: The interpretive report will include specimen information, assay information,
background information, and conclusions based on the test results (negative, heterozygous MTHFR
C677T, homozygous MTHFR C677T; negative, heterozygous MTHFR A1298C, homozygous MTHFR
A1298C).
Reference Values:
Negative
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 36
Thrombophilia: clinical and laboratory assessment and management. In Consultative Hemostasis and
Thrombosis. Fourth edition. Edited by CS Kitchens, BM Alving, CM Kessler. Saunders, 2012
Useful For: Direct mutation analysis for the MTHFR C677T mutation should be reserved for patients
with coronary artery disease, acute myocardial infarction, peripheral vascular artery disease, stroke, or
venous thromboembolism who have increased basal homocysteine levels or an abnormal
methionine-load test.
Interpretation: The interpretive report will include specimen information, assay information,
background information, and conclusions based on the test results (negative, heterozygous MTHFR
C677T, homozygous MTHFR C677T).
Reference Values:
Negative
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 37
Concerns with toxicity (bone marrow suppression, hepatic dysfunction) and development of fungal
resistance limit the use of flucytosine, particularly as a monotherapy. The drug is well-absorbed orally,
but can also be administered intravenously (available outside of the United States). There is good
correlation between serum concentrations of flucytosine with both efficacy and risk for toxicity.
Because of the drugs short half-life (3-6 hours), therapeutic monitoring is typically performed at peak
levels, 1 to 2 hours after an oral dose or 30 minutes after an intravenous administration. Flucytosine is
eliminated primarily as unmetabolized drug in urine. Patients with renal dysfunction may require dose
adjustments or more frequent monitoring to ensure that serum concentrations do not accumulate to
excessive levels. Nephrotoxicity associated with use of amphotericin B can affect elimination of
flucytosine when the drugs are coadministered.
Useful For: Monitoring serum concentration during therapy Evaluating potential toxicity May be
useful to evaluate patient compliance
Interpretation: Most individuals display optimal response to flucytosine when peak serum levels (1-2
hours after oral dosing) are greater than 25.0 mcg/mL. Some infections may require higher concentrations
for efficacy. Toxicity is more likely when peak serum concentrations are greater than 100.0 mcg/mL
Reference Values:
Therapeutic concentration:
Peak >25.0 mcg/mL (difficult infections may require higher concentrations)
Toxic concentration:
Peak >100.0 mcg/mL
Clinical References: 1. Goodwin ML, Drew RH: Antifungal serum concentration monitoring: an
update. J Antimicrob Chemother 2008;61:17-25 2. Andes D, Pascual A, Marchetti O: Antifungal
therapeutic drug monitoring: established and emerging indications. Antimicrob Agents Chemother
2009;53(1):24-34
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 38
Interpretation: Elevated excretion of 5-hydroxyindoleacetic acid is a probable indicator of the
presence of a serotonin-producing tumor, if pharmacological and dietary artifacts have been ruled out.
Reference Values:
< or =8 mg/24 hours
F5M 5-Methyltetrahydrofolate
57101 Reference Values:
5-Methyltetrahydrofolate
Age 5MTHF
(years) (nmol/L)
0-0.2 40-240
0.2-0.5 40-240
0.5-2.0 40-187
2.0-5.0 40-150
5.0-10 40-128
10-15 40-120
Adults 40-120
Note: If test results are inconsistent with the clinical presentation, please call our laboratory to discuss
the case and/or submit a second sample for confirmatory testing.
DISCLAIMER required by the FDA for high complexity clinical laboratories: HPLC testing was
developed and its performance characteristics determined by Medical Neurogenetics. These HPLC tests
have not been cleared or approved by the U.S. FDA.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 39
found in a specimen containing 6-MAM. Opiates, including heroin, have been shown to readily cross
the placenta and distribute widely into many fetal tissues.(4) Opiate use by the mother during pregnancy
increased the risk of prematurity and being small for gestational age. Furthermore, heroin-exposed
infants exhibit an early onset of withdrawal symptoms compared with methadone-exposed infants.
Heroin-exposed infants demonstrate a variety of symptoms including irritability, hypertonia,
wakefulness, diarrhea, yawning, sneezing, increased hiccups, excessive sucking, and seizures.
Long-term intrauterine drug exposure may lead to abnormal neurocognitive and behavioral
development as well as an increased risk of sudden infant death syndrome.(5) The disposition of drug in
meconium is not well understood. The proposed mechanism is that the fetus excretes drug into bile and
amniotic fluid. Drug accumulates in meconium either by direct deposit from bile or through swallowing
of amniotic fluid.(6) The first evidence of meconium in the fetal intestine appears at approximately the
10th to 12th week of gestation, and slowly moves into the colon by the 16th week of gestation.(7)
Therefore, the presence of drugs in meconium has been proposed to be indicative of in utero drug
exposure during the final 4 to 5 months of pregnancy, a longer historical measure than is possible by
urinalysis.(6) Chain of custody is a record of the disposition of a specimen to document who collected
it, who handled it, and who performed the analysis. When a specimen is submitted in this manner,
analysis will be performed in such a way that it will withstand regular court scrutiny.
Useful For: Detection of in utero drug exposure up to 5 months before birth Chain of custody is
required whenever the results of testing could be used in a court of law. Its purpose is to protect the rights
of the individual contributing the specimen by demonstrating that it was under the control of personnel
involved with testing the specimen at all times; this control implies that the opportunity for specimen
tampering would be limited. Since the evidence of illicit drug use during pregnancy can be cause for
separating the baby from the mother, a complete chain-of-custody ensures that the test results are
appropriate for legal proceedings.
Reference Values:
Negative
Positives are reported with a quantitative LC-MS/MS result.
Cutoff concentration:
6-MAM by LC-MS/MS: 5 ng/g
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 40
6-MAM to morphine, the dominant metabolite of heroin.(2,3) Heroin is rarely found intact in urine, since
only 0.1% of a dose is excreted unchanged. 6-MAM is a unique metabolite of heroin, and its presence is a
definitive indication of recent heroin use. Like heroin, 6-MAM has a very short half-life and detection
window.
Reference Values:
Negative
Cutoff concentrations:
6-MAM
<5 ng/mL
Useful For: Determination of heroin use Chain of custody is required whenever the results of testing
could be used in a court of law. Its purpose is to protect the rights of the individual contributing the
specimen by demonstrating that it was under the control of personnel involved with testing the
specimen at all times; this control implies that the opportunity for specimen tampering would be limited.
Reference Values:
Negative
Cutoff concentrations:
6-MAM
<5 ng/mL
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 41
Clinical References: 1. Giovannelli M, Bedforth N, Aitkenhead A: Survey of intrathecal opioid
usage in the UK. Eur J Anaesthesiol 2008;25:118-1122 2. Principles of Forensic Toxicology. Second
edition. Washington DC. AACC Press, 2003, pp 187-205 3. Hardman JG, Limbird LE, Gilman AG:
Goodman and Gilman's. The Pharmacological Basis of Therapeutics. 10th edition New York,
McGraw-Hill Book Company, 2001 pp 590-592
Reference Values:
Negative
Positives are reported with a quantitative LC-MS/MS result.
Cutoff concentration:
6-MAM by LC-MS/MS: 5 ng/g
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 42
Gynecol Surv 2005 Jan;60(1):45-56; quiz 73-74
Reference Values:
Qualitative test Positive or Negative
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 43
ACARP Acanthamoeba species Molecular Detection, PCR, Ocular
64717 Clinical Information: Acanthamoeba are ubiquitous, free-living, microscopic amebae that cause rare
but severe infections of the eye, skin, lungs, and central nervous system (CNS). They are found
worldwide in water and soil and may enter the body through inhalation, contamination of wounds, and
contact lens use. As many as 24 species comprising 18 genotypes (T1-T18) have been described, although
most human infections are due to genotype T4. Given their widespread distribution in the environment,
many people will be exposed to Acanthamoeba during their lifetime, but very few will become sick from
this exposure. The most common form of Acanthamoeba infection is amebic keratitis (AK). Infection
occurs primarily in contact lens wearers due to contamination of lenses, cleaning solutions, or storage
cases. Amebae can also enter the cornea following trauma. AK is a painful, sub-acute corneal infection
associated with extensive scarring and blindness if untreated. Cases generally respond to treatment but
relapse is common. Compared to corneal infection, involvement of the CNS is rare and seen primarily in
severely immunocompromised individuals such as organ transplant recipients and patients with AIDS.
CNS infection may also be caused by a related ameba, Balamuthia mandrillaris. AK is usually suspected
clinically based on symptoms and confocal ophthalmologic examination. Confirmation of infection is
classically identified made by microscopic examination and culture of corneal tissue and contact lenses or
equipment using tap water agar plate overlain with bacteria as a food source for the amebae.
Unfortunately, it must be held and examined for 7 days for maximum sensitivity. PCR provides a more
rapid result with similar sensitivity to culture and is therefore the preferred method for confirming the
clinical diagnosis of AK.
Useful For: Aid in the diagnosis of amebic keratitis in conjunction with clinical findings
Interpretation: A positive result indicates the presence of Acanthamoeba species DNA and is
consistent with active or recent infection. While positive results are highly specific indicators of disease,
they should be correlated with symptoms, clinical findings, and confocal ophthalmologic examination.
Reference Values:
Negative
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Reference Values:
Therapeutic: <30 mcg/mL
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 45
Toxic: >150 mcg/mL 4 hours after dose
Clinical References: Rumack BH, Peterson RG: Acetaminophen overdose: incidence, diagnosis,
and management in 416 patients. Pediatrics Nov 1978;62:898-903
Order MPCT / Muscle Pathology Consultation or MBCT / Muscle Biopsy Consultation, Outside Slides
and/or Paraffin Blocks. The consultant will determine the need for special stains.
Acetoacetate
Normal range for adults: 5-30 mcg/mL
Useful For: Confirming the diagnosis of myasthenia gravis (MG) Distinguishing acquired disease
(90% positive) from congenital disease (negative) Detecting subclinical MG in patients with thymoma or
graft-versus-host disease Monitoring disease progression in MG or response to immunotherapy An
adjunct to the test for P/Q-type calcium channel binding antibodies as a diagnostic aid for Lambert-Eaton
myasthenic syndrome (LES) or primary lung carcinoma
Interpretation: Values >0.02 nmol/L are consistent with a diagnosis of acquired myasthenia gravis
(MG), provided that clinical/electrophysiological criteria support that diagnosis. The assay for muscle
acetylcholine receptor (AChR) binding antibodies is positive in approximately 90% of
nonimmunosuppressed patients with generalized MG. The frequency of antibody detection is lower in
MG patients with weakness clinically restricted to ocular muscles (71%), and antibody titers are generally
low in ocular MG (eg, 0.03-1.0 nmol/L). Results may be negative in the first 12 months after symptoms of
MG appear or during immunosuppressant therapy. Note: In follow up of seronegative patients with
adult-acquired generalized MG, 17.4% seroconvert to positive at 12 months (ie, seronegativity rate at 12
months is 8.4%). Of persistently seronegative patients, 38% have muscle-specific kinase (MuSK)
antibody. Sera of nonmyasthenic subjects bind per liter 0.02 nmol or less of muscle AChR complexed
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 46
with (125)I-labeled-alpha-bungarotoxin. In general, there is not a close correlation between antibody titer
and severity of weakness, but in individual patients, clinical improvement is usually accompanied by a
decrease in titer.
Reference Values:
< or =0.02 nmol/L
Clinical References: 1. Lennon VA: Serological diagnosis of myasthenia gravis and distinction
from the Lambert-Eaton myasthenic syndrome. Neurology 1997;48(Suppl 5):S23-S27 2. Lachance DH,
Lennon VA: Chapter 19, Paraneoplastic neurological autoimmunity. In Neuroimmunology in Clinical
Practice. Edited by B Kalman, T Brannagan III. Blackwell Publishing Ltd, 2008, pp 210-217
Useful For: Diagnosing open neural tube defects, and to a lesser degree, ventral wall defects
Interpretation: The presence of acetylcholinesterase in amniotic fluid is consistent with open neural
tube defects and, to a lesser degree, ventral wall defects.
Reference Values:
Negative (reported as negative [normal] or positive [abnormal] for inhibitable acetylcholinesterase)
Reference values were established in conjunction with alpha-fetoprotein testing and include only
amniotic fluids from pregnancies between 14 and 21 weeks gestation.
Clinical References: Wilson RD, Audibert F, Brock JA, et al: Prenatal screening, diagnosis, and
pregnancy management of fetal neural tube defects. J Obstet Gynaecol Can 2014 Oct;36(10):927-939
Useful For: Detecting effects of remote (months) past exposure to cholinesterase inhibitors
(organophosphate insecticide poisoning)
Interpretation: Activities less than normal are suspect for exposure to certain insecticides.
Reference Values:
31.2-61.3 U/g of hemoglobin
Clinical References: 1. Robinson DG, Trites DG, Banister EW: Physiological effects of work stress
and pesticide exposure in tree planting by British Columbia silviculture workers. Ergonomics
1993;36:951-961 2. Fuortes LJ, Ayebo AD, Kross BC: Cholinesterase-inhibiting insecticide toxicity. Am
Fam Phys 1993;47:1613-1620
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 48
This leads to an accumulation of glycogen in the lysosome causing swelling, cell damage, and progressive
organ dysfunction. Pompe disease is caused by mutations in the GAA gene, and it is characterized by
muscle hypotonia, weakness, cardiomegaly, hypertrophic cardiomyopathy, and eventual death due to
either cardiorespiratory or respiratory failure. The clinical phenotype, in general, appears to be dependent
on residual enzyme activity, with complete loss of activity causing onset in infancy. Untreated, this leads
to death, typically within the first year of life. Juvenile and adult-onset forms are characterized by later
onset and longer survival. Primary symptoms of later-onset Pompe disease include muscle weakness and
respiratory insufficiency. Rarely, clinically significant cardiomyopathy can be seen. The estimated
incidence is 1 in 40,000 live births. Enzyme replacement therapy (ERT) improves outcome in many
patients with either classic infantile onset or later onset forms of Pompe disease. Early initiation of
treatment improves the prognosis and makes early diagnosis of Pompe disease desirable. Because of this,
newborn screening for Pompe disease has recently been implemented in some states. The early
identification and treatment of infants with Pompe disease has been shown to be helpful in reducing the
morbidity and mortality associated with this disease. Since Pompe disease is considered a rare condition
that progresses rapidly in infancy, the disease, in particular the juvenile and adult-onset forms, is often
considered late if at all, during the evaluation of patients presenting with proximal muscle weakness and
respiratory insufficiency. Testing traditionally required a skin or muscle biopsy to establish cultures for
enzyme testing. More recently, molecular genetic testing of the GAA gene (GAAZ / Pompe Disease, Full
Gene Analysis) became clinically available. Determination of the enzyme activity in dried blood spot
specimens can be performed in a timely fashion and provide better guidance in the decision to submit
samples for further confirmatory testing by molecular genetic analysis (GAAZ / Pompe Disease, Full
Gene Analysis).
Useful For: Evaluation of patients of any age with a clinical presentation suggestive of Pompe
disease (muscle hypotonia, weakness, or cardiomyopathy)
Interpretation: Normal results (>0.5 nmol/hour/mL) in properly submitted specimens are not
consistent with classic Pompe disease. Affected individuals typically have levels of 0.5 nmol/hour/mL
or less; however, some later onset cases may show higher enzyme activity. Results of 0.5 nmol/hour/mL
or less can be followed up by molecular genetic analysis of the GAA gene (GAAZ / Pompe Disease,
Full Gene Analysis) to determine carrier, pseudodeficiency, or disease status.
Reference Values:
Normal >0.5 nmol/mL/hour
Clinical References: 1. Chien YH, Hwu WL, Lee NC: Pompe Disease: early diagnosis and early
treatment make a difference. Pediatr Neonatol 2013;54:219-227 2. Gungor D, Kruijshaar ME, Plug I, et
al: Quality of life and participation in daily life of adults with Pompe Disease receiving enzyme
replacement therapy: 10 years of international follow-up. J Inher Metab Dis 2015 Nov;38:495-503 3.
Katzin LW, Amato AA: Pompe disease: a review of the current diagnosis and treatment
recommendations in the era of enzyme replacement therapy. J Clin Neuromuscul Dis 2008
Jun;9(4):421-431 4. Enns GM, Steiner RD, Cowan TM: Lysosomal disorders. In Pediatric
Endocrinology and Inborn Errors of Metabolism. Edited by K Sarafoglou, GF Hoffmann, KS Roth.
McGraw-Hill, Medical Publishing Division, 2009, pp 750-751 5. Matern D, Gavrilov D, Oglesbee D, et
al: Newborn screening for lysosomal storage disorders. Semin Perinatol 2015 Apr;39(3):206-216
Order MPCT / Muscle Pathology Consultation or MBCT / Muscle Biopsy Consultation, Outside
Slides and/or Paraffin Blocks. The consultant will determine the need for special stains.
Reference Values:
Negative (reported as positive or negative)
Useful For: Identification of cells expressing the alpha-smooth muscle isoform of actin
Interpretation: This test includes only technical performance of the stain (no pathologist interpretation
is performed). If diagnostic consultation by a pathologist is required, order 70012 / Pathology
Consultation. The positive and negative controls are verified as showing appropriate immunoreactivity. If
a control tissue is not included on the slide, a scanned image of the relevant quality control tissue is
available upon request; contact 855-516-8404. Interpretation of this test should be performed in the
context of the patient's clinical history and other diagnostic tests by a qualified pathologist.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 50
and female genital tracts. Their presence is important in preserving the usual bacterial populations of the
mouth and in preventing infection with pathogenic bacteria. Actinomyces are generally of low
pathogenicity but may be an important factor in the development of periodontal disease and may cause
soft tissue infections in colonized areas of the body following trauma (surgical or otherwise). The typical
lesion consists of an outer zone of granulation around central purulent loculations containing masses of
tangled organisms ("sulfur granule"). Chronic burrowing sinus tracts develop. Typical actinomycotic
infections occur around the head and neck, in the lung and chest wall, and in the peritoneal cavity and
abdominal wall. Actinomycosis of the female genital tract occurs in association with use of intrauterine
contraceptive devices. Purulent collections containing "sulfur granules" may drain from some sinus tracts
opening to the skin.
Reference Values:
No growth
Identification of probable pathogens
Clinical References: 1. Summanen P, Baron EJ, Citron DM, Jousimies-Somer HR, et al:
Wadsworth Anaerobic Bacteriology Manual, Sixth edition. Belmont CA, Star Publishing Co. 2002 2..
Hall V, Copsey SD: Propionibacterium, Lactobacillus, Actinomyces, and Other Non-Spore-Forming
Anaerobic Gram-Positive Rods. In Manual of Clinical Microbiology. 11th edition. Edited by J
Jorgensen. Washington DC, ASM Press, 2015 Chapters 52, pp 920-939 3. Morton A, Hall, GS:
Anaerobic Gram-Positive Bacilli. In Clinical Microbiology Procedures Handbook. Third edition. Vol. 1.
Edited by LS Garcia. Washington DC, ASM Press, 2010
Useful For: Monitoring heparin therapy (unfractionated heparin) Screening for certain coagulation
factor deficiencies Detection of coagulation inhibitors such as lupus anticoagulant, specific factor
inhibitors, and nonspecific inhibitors
Interpretation: Prolongation of the activated partial thromboplastin time (APTT) can occur as a
result of deficiency of one or more coagulation factors (acquired or congenital in origin), or the
presence of an inhibitor of coagulation such as heparin, a lupus anticoagulant, a nonspecific inhibitor
such as a monoclonal immunoglobulin, or a specific coagulation factor inhibitor. Prolonged clotting
times may also be observed in cases of fibrinogen deficiency, liver disease, and vitamin K deficiency.
Shortening of the APTT usually reflects either elevation of factor VIII activity in vivo that most often
occurs in association with acute or chronic illness or inflammation, or spurious results associated with
either difficult venipuncture and specimen collection or suboptimal specimen processing.
Reference Values:
25-37 seconds
Clinical References: 1. Clinical and Laboratory Standards Institute (CLSI). One-stage PT and
APTT test; Approved Guideline Second Edition. H47-A2, 2008 2. Greaves M, Preston FE: Approach to
the bleeding patient. In Hemostasis and Thrombosis: Basic Principles and Clinical Practice. Fourth
edition. Edited by RW Colman, J Hirsh, VJ Marder, et al. Philadelphia, JB Lippincott Co, 2001, pp
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1197-1234
Useful For: Evaluation of patients with incident or recurrent venous thromboembolism (VTE)
Evaluation of individuals with a family history of VTE
Interpretation: An activated protein C (APC) resistance ratio of <2.3 suggests abnormal resistance to
APC of hereditary origin. If the APC resistance test is abnormal, DNA-based testing for the factor V
Leiden mutation (F5DNA / Factor V Leiden [R506Q] Mutation, Blood) may be helpful in confirming or
excluding hereditary APC-resistance.
Reference Values:
APCRV RATIO
> or =2.3
Pediatric reference range has neither been established nor is available in scientific literature. The adult
reference range likely would be applicable to children older than 6 months.
Clinical References: 1. Nichols WL, Heit JA: Activated protein C resistance and thrombosis. Mayo
Clin Proc 1996;71:897-898 2. Dahlback B: Resistance to activated protein C as risk factor for thrombosis:
molecular mechanisms, laboratory investigation, and clinical management. Semin Hematol
1997;34(3):217-234 3. Rodeghiero F, Tosetto A: Activated protein C resistance and Factor V Leiden
mutation are independent risk factors for venous thromboembolism. Ann Intern Med 1999;130:643-650 4.
Grody WW, Griffin JH, Taylor AK, et al: American College of Medical Genetics consensus statement on
factor V Leiden mutation testing. Genet Med 2001;3:139-148 5. Press RD, Bauer KA, Kujovich JL, Heit
JA: Clinical utility of factor V Leiden (R506Q) testing for the diagnosis and management of
thromboembolic disorders. Arch Pathol Lab Med 2002;126:1304-1318
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Clinical Information: Protein C, a part of the natural anticoagulant system, is a vitamin
K-dependent protein zymogen (molecular weight=62,000 da) that is synthesized in the liver and
circulates at a plasma concentration of approximately 5 mcg/mL. Protein C is activated to activated
protein C (APC) via proteolytic cleavage by thrombin bound to thrombomodulin, an endothelial cell
surface membrane protein. APC downregulates the procoagulant system by proteolytically inactivating
procoagulant factors Va and VIIIa. Protein S, another vitamin K-dependent coagulation protein,
catalyzes APC inactivation of factors Va and VIIIa. APC interacts with and proteolyses factors V/Va
and VIII/VIIIa at specific APC binding and cleavage sites, respectively. Resistance to activated protein
C (APC resistance) is a term used to describe abnormal resistance of human plasma to the anticoagulant
effects of human APC. APC resistance is characterized by a reduced anticoagulant response of patient
plasma after adding a standard amount of APC. For this assay, the activated partial thromboplastin time
clotting test fails to prolong significantly after the addition of APC. The vast majority of individuals
with familial APC resistance have a specific point mutation in the procoagulant factor V gene
(1691G->A, factor V Leiden) encoding for a glutamine (Q) substitution for arginine (R)-506 in the
heavy chain of factor V (factor V R506Q). This amino acid change alters an APC cleavage site on
factor V such that factor V/Va is partially resistant to inactivation by APC. The carrier frequency for the
factor V Leiden mutation varies depending on the population. Approximately 5% of asymptomatic
white Americans of non-Hispanic ancestry are heterozygous carriers, while the carrier frequency among
African Americans, Asian Americans, and Native Americans is <1%, and the carrier frequency for
Hispanics is intermediate (2.5%). The carrier frequency can be especially high (up to 14%) among
whites of Northern European or Scandinavian ancestry. Homozygosity for factor V Leiden is much less
common, but may confer a substantially increased risk for thrombosis. The degree of abnormality of the
APC-resistance assay correlates with heterozygosity or homozygosity for the factor V Leiden mutation;
homozygous carriers have a very low APC-resistance ratio (eg, 1.1-1.4), while the ratio for
heterozygous carriers is usually 1.5 to 1.8.
Useful For: Evaluation of patients with incident or recurrent venous thromboembolism (VTE)
Evaluation of individuals with a family history of VTE
Interpretation: An activated protein C (APC) resistance ratio of <2.3 suggests abnormal resistance
to APC of hereditary origin. If the screening APC resistance test is abnormal, DNA-based testing for the
factor V Leiden mutation (F5DNA / Factor V Leiden [R506Q] Mutation, Blood) is performed to
confirm or exclude hereditary APC-resistance.
Reference Values:
APCRV RATIO
> or =2.3
Pediatric reference range has neither been established nor is available in scientific literature. The adult
reference range likely would be applicable to children older than 6 months.
Clinical References: 1. Nichols WL, Heit JA: Activated protein C resistance and thrombosis.
Mayo Clin Proc 1996;71:897-898 2. Dahlback B: Resistance to activated protein C as risk factor for
thrombosis: molecular mechanisms, laboratory investigation, and clinical management. Semin Hematol
1997;34(3):217-234 3. Rodeghiero F, Tosetto A: Activated protein C resistance and Factor V Leiden
mutation are independent risk factors for venous thromboembolism. Ann Intern Med 1999;130:643-650
4. Grody WW, Griffin JH, Taylor AK, et al: American College of Medical Genetics consensus
statement on factor V Leiden mutation testing. Genet Med 2001;3:139-148 5. Press RD, Bauer KA,
Kujovich JL, Heit JA: Clinical utility of factor V Leiden (R506Q) testing for the diagnosis and
management of thromboembolic disorders. Arch Pathol Lab Med 2002;126:1304-1318
Reference Values:
HEPATITIS B SURFACE ANTIGEN
Negative
Interpretation depends on clinical setting. See Viral Hepatitis Serologic Profiles in Special Instructions.
Clinical References: 1. Roque-Afonso AM, Desbois D, Dussaix E: Hepatitis A virus: serology and
molecular diagnostics. Future Virology 2010;5(2):233-242 2. De Paula VS: Laboratory diagnosis of
hepatitis A. Future Virology 2012;7(5):461-472 3. Bonino F, Piratvisuth T, Brunetto MR, et al:
Diagnostic markers of chronic hepatitis B infection and disease. Antiviral Therapy 2010;15(Suppl.
3):35-44 4. Wasley A, Fiore A, Bell BP: Hepatitis A in the era of vaccination. Epidemiol Rev
2006;28:101-111 5. American Association for the Study of Liver Diseases/Infectious Diseases Society of
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 54
America/International Antiviral Society-USA. Recommendations for Testing, Managing, and Treating
Hepatitis C. Accessed on January 27, 2015. Available at www.hcvguidelines.org
Useful For: Detecting a neoplastic clone associated with the common chromosome abnormalities
seen in patients with acute myeloid leukemia or other myeloid malignancies Evaluating specimens in
which standard cytogenetic analysis is unsuccessful Identifying and tracking known chromosome
abnormalities in patients with myeloid malignancies and tracking response to therapy
Interpretation: A neoplastic clone is detected when the percent of cells with an abnormality exceeds
the normal reference range for any given probe. Detection of an abnormal clone likely indicates a
diagnosis of an acute myeloid leukemia of various subtypes. The absence of an abnormal clone does not
rule out the presence of a neoplastic disorder.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Grimwade D, Hills RK, Moorman AV, et al: Refinement of cytogenetics
classification in acute myeloid leukemia: determination of prognostic significance or rare recurring
chromosomal abnormalities among 5879 younger adult patients treated in the United Kingdom
Research Council trials. Blood 2010 Jul;116(3):354-365 2. International Agency for Research on
Cancer (IARC): World Health Organization (WHO) classification of tumour of haematopoietic and
lymphoid tissues. Edited by SH Swerdlow, E Campo, NL Harris, et al. IARC Press, Oxford: Oxford
University Press (distributor), 2008
Useful For: Confirmation of acute porphyria for patients with clinical features of the disease
Interpretation: All detected alterations are evaluated according to American College of Medical
Genetics recommendations.(1) Variants are classified based on known, predicted, or possible
pathogenicity and reported with interpretive comments detailing their potential or known significance.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for
standards of interpretation and reporting of sequence variations: revisions 2007. Genet Med
2008;10(4):294-300 2. Siegesmund M, van Tuyll van Serooskerken AM, Poblete-Gutierrez P, Frank J:
The acute hepatic porphyrias: current status and future challenges. Best Pract Res Clin Gastroenterol 2010
Oct;24(5):593-605 3. Anderson KE, Bloomer JR, Bonkovsky HL, et al: Recommendations for the
diagnosis and treatment of the acute porphyrias. Ann Intern Med 2005 Mar 15;142(6):439-450
Usual therapeutic range (vs. Genital Herpes) during chronic oral daily divided dosages of 1200 2400
mg:
Peak: 0.40 2.0 mcg/mL plasma
Trough: 0.14 1.2 mcg/mL plasma
Useful For: Diagnosis of fatty acid oxidation disorders and several organic acidurias Evaluating
treatment during follow-up of patients with fatty acid beta-oxidation disorders and several organic
acidurias
Interpretation: An interpretive report is provided. The individual quantitative results support the
interpretation of the acylcarnitine profile but are not diagnostic by themselves. The interpretation is
based on pattern recognition. Abnormal results are not sufficient to conclusively establish a diagnosis of
a particular disease. To verify a preliminary diagnosis based on an acylcarnitine analysis, independent
biochemical (eg, in vitro enzyme assay) or molecular genetic analyses are required. For information on
the follow-up of specific acylcarnitine elevations, see Special Instructions for the following algorithms:
-Newborn Screening Follow-up for Elevations of C8, C6, and C10 Acylcarnitines (also applies to any
plasma C8, C6, and C10 acylcarnitine elevations) -Newborn Screening Follow-up for Isolated C4
Acylcarnitine Elevations (also applies to any plasma C4 acylcarnitine elevation) -Newborn Screening
Follow-up for Isolated C5 Acylcarnitine Elevations (also applies to any plasma C5 acylcarnitine
elevation)
Reference Values:
< or =7 days 8 days-7 years > or =8 years
(nmol/mL) (nmol/mL) (nmol/mL)
Acrylylcarnitine, C3:1
Propionylcarnitine, C3
Formiminoglutamate, FIGLU
Iso-/Butyrylcarnitine, C4
Tiglylcarnitine, C5:1
Isovaleryl-/2-Methylbutyrylcarn C5
3-OH-iso-/butyrylcarnitine, C4-OH
Hexenoylcarnitine, C6:1
Hexanoylcarnitine, C6
3-OH-isovalerylcarnitine, C5-OH
Benzoylcarnitine
Heptanoylcarnitine, C7
3-OH-hexanoylcarnitine, C6-OH
Phenylacetylcarnitine
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Salicylcarnitine
Octenoylcarnitine, C8:1
Octanoylcarnitine, C8
Malonylcarnitine, C3-DC
Decadienoylcarnitine, C10:2
Decenoylcarnitine, C10:1
Decanoylcarnitine, C10
Methylmalonyl-/succinylcarn, C4-DC
3-OH-decenoylcarnitine, C10:1-OH
Glutarylcarnitine, C5-DC
Dodecenoylcarnitine, C12:1
Dodecanoylcarnitine, C12
3-Methylglutarylcarnitine, C6-DC
3-OH-dodecenoylcarnitine, C12:1-OH
3-OH-dodecanoylcarnitine, C12-OH
Tetradecadienoylcarnitine, C14:2
Tetradecenoylcarnitine, C14:1
Tetradecanoylcarnitine, C14
Octanedioylcarnitine, C8-DC
3-OH-tetradecenoylcarnitine C14:1OH
3-OH-tetradecanoylcarnitine, C14-OH
Hexadecenoylcarnitine, C16:1
Hexadecanoylcarnitine, C16
3-OH-hexadecenoylcarnitine,C16:1-OH
3-OH-hexadecanoylcarnitine, C16-OH
Octadecadienoylcarnitine, C18:2
Octadecenoylcarnitine, C18:1
Octadecanoylcarnitine, C18
Dodecanedioylcarnitine, C12-DC
3-OH-octadecadienoylcarn, C18:2-OH
3-OH-octadecenoylcarnitine C18:1-OH
3-OH-octadecanoylcarnitine, C18-OH
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ACYLG Acylglycines, Quantitative, Urine
81249 Clinical Information: Acylglycines are glycine conjugates of acyl-CoA species. Acylglycines are
normal intermediates of amino acid and fatty acid metabolism; however, in abnormal concentrations
acylglycines are biochemical markers of selected inborn errors of metabolism (IEM). Analysis of
acylglycines is a useful screening test in the evaluation of patients with a suspected IEM, though
additional studies are necessary to establish a diagnosis. The biochemical diagnosis of these disorders is
a complex process achieved by multiple tests and their integrated interpretation. Although acylglycines
are often ordered in conjunction with organic acids, acylglycine analysis is more sensitive and specific
for the identification of asymptomatic patients and those with mild and/or intermittent biochemical
phenotypes that could be missed by organic acid analysis alone. The quantitative analysis of urinary
acylglycines is particularly effective for identifying asymptomatic patients affected with disorders
including: -Short chain acyl-CoA dehydrogenase (SCAD) deficiency -Medium-chain acyl-CoA
dehydrogenase (MCAD) deficiency -Medium-chain 3-ketoacyl-CoA thiolase (MCKAT) deficiency
-Glutaric acidemia type II -Ethylmalonic encephalopathy -2-Methylbutyryl-CoA dehydrogenase
deficiency -Isovaleryl-CoA dehydrogenase deficiency -Glutaryl-CoA dehydrogenase deficiency
Useful For: Biochemical screening of asymptomatic patients affected with 1 of the following inborn
errors of metabolism: -Short chain acyl-CoA dehydrogenase (SCAD) deficiency -Medium-chain
acyl-CoA dehydrogenase (MCAD) deficiency -Medium-chain 3-ketoacyl-CoA thiolase (MCKAT)
deficiency -Glutaric acidemia type II -Ethylmalonic encephalopathy -2-Methylbutyryl-CoA
dehydrogenase deficiency -Isovaleryl-CoA dehydrogenase deficiency -Glutaryl-CoA dehydrogenase
deficiency
Interpretation: When abnormal results are detected, a detailed interpretation is given, including an
overview of the results and of their significance; a correlation to available clinical information; elements
of differential diagnosis; recommendations for additional biochemical testing and in vitro confirmatory
studies (enzyme assay, molecular analysis); name and phone number of key contacts who may provide
these studies at Mayo Clinic or elsewhere; and a phone number to reach one of the laboratory directors
in case the referring physician has additional questions.
Reference Values:
Control Values Results Expressed as mg/g Creatinine
Range
Isobutyrylglycine 0.00-11.0
n-Butyrylglycine 0.1-2.1
2-Methylbutyrylglycine 0.3-7.5
Isovalerylglycine 0.3-14.3
n-Hexanoylglycine 0.2-1.9
n-Octanoylglycine 0.1-2.1
3-Phenylpropionylglycine 0.00-1.1
Suberylglycine 0.00-11.0
trans-Cinnamoylglycine 0.2-14.7
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 59
Clinical References: 1. Rinaldo P: Laboratory diagnosis of inborn errors of metabolism. In Liver
Disease in Children. Second edition. Edited by FJ Suchy. Philadelphia, Lippincott, Williams and Wilkins,
2001, pp 171-184 2. Rinaldo P, Hahn SH, Matern D: Inborn errors of amino acid, organic acid, and fatty
acid metabolism. In Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Fourth edition.
Edited by CA Burtis, ER Ashwood, DE Bruns. WB Saunders Company, 2005, pp 2207-2247 3. Rinaldo
P: Organic Acids. In Laboratory Guide to the Methods in Biochemical Genetics. Edited by N Blau, M
Duran, KM Gibson. Springer-Verlag Berlin Heidelberg, 2008, pp 137-170
In the presence of anti-adalimumab antibodies, they adalimumab drug level reflects the
antibody-unbound fraction of adalimumab concentration in serum.
Anti-Adalimumab Antibody
-Quantitation Limit: <25 ng/mL
Results of 25 or higher indicates detection of anti-adalimumab antibodies.
Useful For: Assisting with the diagnosis of congenital or acquired thrombotic thrombocytopenic
purpura
Reference Values:
ADAMTS13 ACTIVITY ASSAY
> or =70%
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ADAMTS13 INHIBITOR SCREEN
Negative
Clinical References: 1. Sadler JE: Von Willebrand factor, ADAMTS13, and thrombotic
thrombocytopenic purpura. Blood 2008 Jul 1;112(1):11-18 2. George JN: How I treat patients with
thrombotic thrombocytopenic purpura: 2010. Blood 2010 Nov 18;116(20):4060-4069 3. Upshaw JD, Jr:
Congenital deficiency of a factor in normal plasma that reverses microangiopathic hemolysis and
thrombocytopenia. N Engl J Med 1978 Jun 15;298(24):1350-1352
Clinical References:
Interpretive Criteria:
<1:8 Antibody Not Detected
> or =1:8 Antibody Detected
Single titers of > or =1:64 are indicative of recent or current infection. Titers of 1:8-1:32 may be
indicative of either past or recent infection, since CF antibody levels persist for only a few months. A
four-fold or greater increase in titer between acute and convalescent specimens confirms the diagnosis.
A positive test result in association with diarrhea highly suggests that Adenovirus is the cause of the
gastroenteritis. Adenovirus may shed asymptomatically up to 18 months after infection. The virus may
also become latent, then reactivate. If the patient, in fact, has a bacterial enterocolitis due to
Staphylococcus aureus, high levels of the bacterial protein A may cross-react with this test and result in a
false positive.
Clinical References: 1. Wu E, Nemerow GR: Virus yoga: the role of flexibility in virus host cell
recognition. Trends Microbiol 2004;124(4):162-169 2. Ohori NP, Michaels MG, Jaffe R, et al:
Adenovirus pneumonia in lung transplant recipients. Hum Pathol 1995;26(10):1073-1079 3. Koneru B,
Jaffe R, Esquivel CO, et al: Adenoviral infections in pediatric liver transplant recipients. JAMA
1987;258(4):489-492
Reference Values:
Negative
Clinical References: 1. Ebner K, Pinsker W, Lion T: Comparative sequence analysis of the hexon
gene in the entire spectrum of human adenovirus serotypes: phylogenetic, taxonomic, and clinical
implications. J Virol 2005;79:12635-12642 2. Ebner K, Suda M, Watzinger F, Lion T: Molecular
detection and quantitative analysis of the entire spectrum of human adenoviruses by a two-reaction
real-time PCR assay. J Clin Microbiol 2005;43:3049-3053 3. Jothikumar N, Cromeans TL, Hill VR, et
al: Quantitative real-time PCR assays for the detection of human adenoviruses and identification of
serotypes 40 and 41. Appl Environ Microbiol 2005;71:3131-3136 4. Robinson C, Echavarria M:
Adenovirus. In Manual of Clinical Microbiology. Edited by PR Murray, EJ Baron, JH Jorgensen, et al:
Ninth edition. Washington, DC, ASM Press, 2007, pp 1589-1600 5. Thavagnanam S, Christie SN,
Doherty GM, et al: Respiratory viral infection in lower airways o asymptomatic children. Acta Paediatr
Mar;99(3):394-398 6. Kaneko H, Maruko I, Iida T, et al: The possibility of human adenovirus detection
in the conjunctiva in asymptomatic cases during a nosocomial infection. Cornea Jun
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2008;27(5):527-530
Reference Values:
Negative
Clinical References: 1. Ebner K, Pinsker W, Lion T: Comparative sequence analysis of the hexon
gene in the entire spectrum of human adenovirus serotypes: phylogenetic, taxonomic, and clinical
implications. J Virol 2005;79:12635-12642 2. Ebner K, Suda M, Watzinger F, Lion T: Molecular
detection and quantitative analysis of the entire spectrum of human adenoviruses by a two-reaction
real-time PCR assay. J Clin Microbiol 2005;43:3049-3053 3. Jothikumar N, Cromeans TL, Hill VR, et al:
Quantitative real-time PCR assays for the detection of human adenoviruses and identification of serotypes
40 and 41. Appl Environ Microbiol 2005;71:3131-3136 4. Robinson C, Echavarria M: Adenovirus. In
Manual of Clinical Microbiology. Edited by PR Murray, EJ Baron, JH, et al: Washington, DC, ASM
Press, 2007, pp 1589-1600 5. Thavagnanam S, Christie SN, Doherty GM, et al: Respiratory viral infection
in lower airways of asymptomatic children. Acta Paediatr 2010 Mar;99(3):394-398 6. Kaneko H, Maruko
I, Iida T, et al: The possibility of human adenovirus detection in the conjunctiva in asymptomatic cases
during a nosocomial infection. Cornea 2008 Jun;27(5):527-530
FADIP Adiponectin
91378 Reference Values:
Reference Ranges for Adiponectin:
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caused by the release of proinflammatory mediators (histamine, leukotrienes, and prostaglandins) from
immunoglobulin E (IgE)-sensitized effector cells (mast cells and basophils) when cell-bound IgE
antibodies interact with allergen. In vitro serum testing for IgE antibodies provides an indication of the
immune response to allergen(s) that may be associated with allergic disease. The allergens chosen for
testing often depend upon the age of the patient, history of allergen exposure, season of the year, and
clinical manifestations. In individuals predisposed to develop allergic disease(s), the sequence of
sensitization and clinical manifestations proceed as follows: eczema and respiratory disease (rhinitis and
bronchospasm) in infants and children less than 5 years due to food sensitivity (milk, egg, soy, and wheat
proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: An aid in the classification of pituitary adenomas and neoplasms with ectopic hormone
production
Interpretation: This test includes only technical performance of the stain (no pathologist
interpretation is performed). If diagnostic consultation by a pathologist is required, order 70012 /
Pathology Consultation. The positive and negative controls are verified as showing appropriate
immunoreactivity. If a control tissue is not included on the slide, a scanned image of the relevant quality
control tissue is available upon request; contact 855-516-8404. Interpretation of this test should be
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performed in the context of the patient's clinical history and other diagnostic tests by a qualified
pathologist.
Clinical References: 1. Hamid Z, Mrak RE, Ijaz MT, Faas FH: Sensitivity and Specificity of
Immunohistochemistry in Pituitary Adenomas. The Endocrinologist 2009;19(1):38-43 2. Osamura RY,
Kajiva H, Takei M, et al: Pathology of the human pituitary adenomas. Histochem Cell Biol
2008;130(3):495-507 3. Scheithauer BW, Jaap AJ, Horvath E, et al: Clinically Silent Corticotroph
Tumors of the Pituitary Gland. Neurosurgery 2000;47(3):723-730
Reference Values:
10-60 pg/mL (a.m. draws)
No established reference values for p.m. draws
Pediatric reference values are the same as adults, as confirmed by peer reviewed literature.
Petersen KE: ACTH in normal children and children with pituitary and adrenal diseases. I. Measurement
in plasma by radioimmunoassay-basal values. Acta Paediatr Scand 1981;70:341-345
Clinical References: 1. Demers LM: In Tietz Textbook of Clinical Chemistry and Molecular
Diagnostics, 2006; pp 2014-2027 2. Petersen KE: ACTH in normal children and children with pituitary
and adrenal diseases I. Measurement in plasma by radioimmunoassay-basal values. Acta Paediatr Scan
1981;70:341-345
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nitrite. Chain of custody is a record of the disposition of a specimen to document who collected it, who
handled it, and who performed the analysis. When a specimen is submitted in this manner, analysis will
be performed in such a way that it will withstand regular court scrutiny. Chain of custody is required
whenever the results of testing could be used in a court of law. Its purpose is to protect the rights of the
individual contributing the specimen by demonstrating that it was under the control of personnel involved
with testing the specimen at all times; this control implies that the opportunity for specimen tampering
would be limited.
Useful For: Assess the possible adulteration of a urine specimen submitted for drug of abuse testing,
as well as for providing the urine creatinine for "creatinine normalization" This chain-of-custody test is
intended to be used in a setting where the test results can be used definitively to make a diagnosis.
Clinical References: 1. MRO Guidance for Interpreting Specimen Validity Test Results.
Washington, DC: Office of the Secretary of Transportation, US Department of Transportation,
September 28, 1998. Memorandum 2. Substance Abuse and Mental Health Services Administration
(SAMHSA) Division of Workplace Programs: Specimen Validity Testing. In Mandatory Guidelines for
Federal Workplace Drug Testing Programs. Federal Register April 13, 2004 (69 FR 19644), effective
November 1, 2004. Memorandum posted: February 2005
Useful For: Assess the possible adulteration of a urine specimen submitted for drug of abuse testing,
as well as for providing the urine creatinine for "creatinine normalization"
Reference Values:
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Immunoglobulin E (IgE)
Reference Ranges (IU/MI)
Age Related Reference Range
1-11 months 0-12
1 year 0-15
2 year 1-29
3 year 4-35
4 year 2-33
5 year 8-56
6 year 3-95
7 year 2-88
8 year 5-71
9 year 3-88
10 year 7-110
11-14 year 7-111
15-19 year 6-96
20-30 year 4-59
31-51 year 5-79
51-80 year 3-48
A 24 year old reference range is shown when no age is given.
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known, but prevalence rates of 1 to 3 per million population and incidences of 0.1 per million/year have
been estimated from population surveys. Biochemical testing is indicated in patients with possible
primary hyperoxaluria. Measurement of urinary oxalate is strongly preferred, with correction to adult
body surface area in pediatric patients (HYOX / Hyperoxaluria Panel, Urine; OXU / Oxalate, 24 Hour,
Urine). Abnormal urinary excretion of oxalate is strongly suggestive of, but not diagnostic for, this
disorder, as there are other forms of inherited (type 2 and non-PH1/PH2) hyperoxaluria and secondary
hyperoxaluria that may result in similarly elevated urine oxalate excretion rates. An elevated urine
glycolate in the presence of hyperoxaluria is suggestive of PH1. Historically, the diagnosis of PH1 was
confirmed by AGT enzyme analysis performed on liver biopsy; however, this has been replaced by
molecular testing, which forms the basis of confirmatory or carrier testing in most cases. PH1 is inherited
as an autosomal recessive disorder caused by mutations in the AGXT gene, which encodes the enzyme
AGT. Several common AGXT mutations have been identified including c.33dupC, p.Gly170Arg
(c.508G->A), and p.Ile244Thr (c.731T->C). These mutations account for at least 1 of the 2 affected
alleles in approximately 70% of individuals with PH1. Direct sequencing of the AGXT gene is predicted
to identify 99% of alleles in individuals who are known by enzyme analysis to be affected with PH1.
While age of onset and severity of disease is variable and not necessarily predictable by genotype, a
correlation between pyridoxine responsiveness and homozygosity for the p.Gly170Arg mutation has been
observed. (Note: testing for the p.Gly170Arg mutation only is available by ordering AGXTG /
Alanine:Glyoxylate Aminotransferase [AGXT] Mutation Analysis [G170R], Blood). Pyridoxine (vitamin
B6) is a known cofactor of AGT and is effective in reducing urine oxalate excretion in some PH1 patients
treated with pharmacologic doses. Individuals with 2 copies of the p.Gly170Arg mutation have been
shown to normalize their urine oxalate when treated with pharmacologic doses of pyridoxine and those
with a single copy of the mutation show reduction in urine oxalate. This is valuable because not all
patients have been shown to be responsive to pyridoxine, and strategies that help to identify the
individuals most likely to benefit from such targeted therapies are desirable.
Useful For: Confirming a diagnosis of primary hyperoxaluria type 1 Carrier testing for individuals
with a family history of primary hyperoxaluria type 1 in the absence of known mutations in the family
Interpretation: All detected alterations are evaluated according to American College of Medical
Genetics recommendations.(1) Variants are classified based on known, predicted, or possible
pathogenicity and reported with interpretive comments detailing their potential or known significance.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for
standards of interpretation and reporting of sequence variations: revisions 2007. Genet Med
2008;10(4):294-300 2. Milliner DS: The primary hyperoxalurias: an algorithm for diagnosis. Am J
Nephrol 2005;25(2):154-160 3. Monico CG, Rossetti S, Olson JB, Milliner DS: Pyridoxine effect in
type I primary hyperoxaluria is associated with the most common mutant allele. Kidney Int
2005;67(5):1704-1709 4. Monico CG, Rossetti S, Schwanz HA, et al: Comprehensive mutation
screening in 55 probands with type 1 primary hyperoxaluria shows feasibility of a gene-based diagnosis.
J Am Soc Nephrol 2007;18:1905-1914 5. Rumsby G, Williams E, Coulter-Mackie M: Evaluation of
mutation screening as a first line test for the diagnosis of the primary hyperoxalurias. Kidney Int
2004;66(3):959-963 6. Williams EL, Acquaviva C, Amoroso, A, et al: Primary hyperoxaluria type I:
update and additional mutation analysis of the AGXT gene. Hum Mutat 2009;30:910-917 7. Williams
E, Rumsby G: Selected exonic sequencing of the AGXT gene provides a genetic diagnosis in 50% of
patients with primary hyperoxaluria type 1. Clin Chem 2007;53(7):1216-1221 8. Communique April
2007: Laboratory and Molecular Diagnosis of Primary Hyperoxaluria and Oxalosis
Useful For: Diagnosis and monitoring of liver disease associated with hepatic necrosis
Interpretation: Elevated alanine aminotransferase (ALT) values are seen in parenchymal liver
diseases characterized by a destruction of hepatocytes. Values are typically at least ten times above the
normal range. Levels may reach values as high as one hundred times the upper reference limit, although
twenty to fifty-fold elevations are most frequently encountered. In infectious hepatitis and other
inflammatory conditions affecting the liver, ALT is characteristically as high as or higher than aspartate
aminotransferase (AST), and the ALT/AST ratio, which normally and in other condition is <1, becomes
greater than unity. ALT levels are usually elevated before clinical signs and symptoms of disease appear.
Reference Values:
Males
> or =1 year: 7-55 U/L
Reference values have not been established for patients who are <12 months of age.
Females
> or =1 year: 7-45 U/L
Reference values have not been established for patients who are <12 months of age.
Useful For: Identifying patients with the pyridoxine responsive form of primary hyperoxaluria type 1
(PH1) Determining the presence of the Gly170Arg (G170R) mutation in the AGXT gene Carrier testing
of at-risk family members
Reference Values:
An interpretive report will be provided.
Useful For: Plasma or serum levels of albumin are frequently used to assess nutritional status
Interpretation: Hyperalbuminemia is of little diagnostic significance except in the case of
dehydration. When plasma or serum albumin values fall below 2.0 g/dL, edema is usually present.
Reference Values:
> or =12 months: 3.5-5.0 g/dL
Reference values have not been established for patients who are <12 months of age.
Synonym(s): Proventil
Methanol (methyl alcohol) concentrations greater than 3 mg/dL are potentially toxic.
Order MPCT / Muscle Pathology Consultation or MBCT / Muscle Biopsy Consultation Outside Slides
and/or Paraffin Blocks. The consultant will determine the need for special stains.
Reference Values:
0-16 years: <14.5 U/L
> or =17 years: <7.7 U/L
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pituitary adrenocorticotropic hormone can stimulate aldosterone secretion. Urinary aldosterone levels are
inversely correlated with urinary sodium excretion. Normal subjects will show a suppression of urinary
aldosterone with adequate sodium repletion. Primary hyperaldosteronism, which may be caused by
aldosterone-secreting adrenal adenoma/carcinomas or adrenal cortical hyperplasia, is characterized by
hypertension accompanied by increased aldosterone levels, hypernatremia, and hypokalemia. Secondary
hyperaldosteronism (eg, in response to renovascular disease, salt depletion, potassium loading, cardiac
failure with ascites, pregnancy, Bartters syndrome) is characterized by increased aldosterone levels
and increased plasma rennin activity.
Useful For: Investigation of primary aldosteronism (eg, adrenal adenoma/carcinoma and adrenal
cortical hyperplasia) and secondary aldosteronism (renovascular disease, salt depletion, potassium
loading, cardiac failure with ascites, pregnancy, Bartter syndrome)
Interpretation: Under normal circumstances, if the 24-hour urinary sodium excretion is >200 mEq,
the urinary aldosterone excretion should be <10 mcg/24 hours. Urinary aldosterone excretion >12
mcg/24 hours as part of an aldosterone suppression test is consistent with hyperaldosteronism. 24-Hour
urinary sodium excretion should exceed 200 mEq to document adequate sodium repletion. See
Renin-Aldosterone Studies in Special Instructions. Note: Advice on stimulation or suppression tests is
available from Mayo Clinic's Division of Endocrinology and may be obtained by calling Mayo Medical
Laboratories.
Reference Values:
ALDOSTERONE
0-30 days: 0.7-11.0 mcg/24 hours*
1-11 months: 0.7-22.0 mcg/24 hours*
> or =1 year: 2.0-20.0 mcg/24 hours
*Loeuille GA, Racadot A, Vasseur P, Vandewalle B: Blood and urinary aldosterone levels in normal
neonates, infants and children. Pediatrie 1981;36:335-344
SODIUM
41-227 mmol/24 hours
If the 24-hour urinary sodium excretion is >200 mmol, the urinary aldosterone excretion should be <10
mcg.
Clinical References: 1. Young WF Jr: Primary aldosteronism: A common and curable form of
hypertension. Cardiol Rev 1999;7:207-214 2. Young WF Jr: Pheochromocytoma and primary
aldosteronism: diagnostic approaches. Endocrinol Metab Clin North Am 1977;26:801-827
Useful For: Investigation of primary aldosteronism (eg, adrenal adenoma/carcinoma and adrenal
cortical hyperplasia) and secondary aldosteronism (renovascular disease, salt depletion, potassium
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loading, cardiac failure with ascites, pregnancy, Bartter syndrome)
Interpretation: Under normal circumstances, if the 24-hour urinary sodium excretion is greater than
200 mEq, the urinary aldosterone excretion should be less than 10 mcg/24 hours. Urinary aldosterone
excretion greater than 12 mcg/24 hours as part of an aldosterone suppression test is consistent with
hyperaldosteronism. 24-Hour urinary sodium excretion should exceed 200 mEq to document adequate
sodium repletion. See Renin-Aldosterone Studies in Special Instructions. Note: Advice on stimulation or
suppression tests is available from Mayo Clinic's Division of Endocrinology and may be obtained by
calling Mayo Medical Laboratories.
Reference Values:
0-30 days: 0.7-11.0 mcg/24 hours*
31 days-11 months: 0.7-22.0 mcg/24 hours*
> or =1 year: 2.0-20.0 mcg/24 hours
*Loeuille GA, Racadot A, Vasseur P, Vandewalle B: Blood and urinary aldosterone levels in normal
neonates, infants and children. Pediatrie 1981;36:335-344
Clinical References: 1. Young WF Jr: Primary aldosteronism: A common and curable form of
hypertension. Cardiol Rev 1999;7:207-214 2. Young WF Jr: Pheochromocytoma and primary
aldosteronism: diagnostic approaches. Endocrinol Metab Clin North Am 1997;26:801-827
Useful For: Investigation of primary aldosteronism (eg, adrenal adenoma/carcinoma and adrenal
cortical hyperplasia) and secondary aldosteronism (renovascular disease, salt depletion, potassium
loading, cardiac failure with ascites, pregnancy, Bartter syndrome)
Interpretation: A high ratio of serum aldosterone (SA) in ng/dL to plasma renin activity (PRA) in
ng/mL per hour, is a positive screening test result, a finding that warrants further testing. An SA/PRA
ratio > or =20 is only interpretable with an SA > or =15 ng/dL and indicates probable primary
aldosteronism. Renal disease, such as unilateral renal artery stenosis, results in elevated renin and
aldosterone levels. Renal venous catheterization may be helpful. A positive test is a renal venous renin
ratio (affected/normal) >1.5. See Renin-Aldosterone Studies and Steroid Pathways in Special Instructions.
Note: Advice on stimulation or suppression tests is available from Mayo Clinic's Division of
Endocrinology and may be obtained by calling Mayo Medical Laboratories.
Reference Values:
No established reference values.
Clinical References: 1. Young WF Jr: Primary aldosteronism: A common and curable form of
hypertension. Cardiol Rev 1999;7:207-214 2. Young WF Jr: Pheochromocytoma and primary
aldosteronism: diagnostic approaches. Endocrinol Metab Clin North Am 1997;26:801-827 3. Hurwitz S,
Cohen RJ, Williams GH: Diurnal variation of aldosterone and plasma renin activity: timing relation to
melatonin and cortisol and consistency after prolonged bed rest. J Appl Physiol 2004;96:1406-1414
Useful For: Investigation of primary aldosteronism (eg, adrenal adenoma/carcinoma and adrenal
cortical hyperplasia) and secondary aldosteronism (renovascular disease, salt depletion, potassium
loading, cardiac failure with ascites, pregnancy, Bartter syndrome)
Interpretation: A high ratio of serum aldosterone (SA) in ng/dL to plasma renin activity (PRA) in
ng/mL per hour, is a positive screening test result, a finding that warrants further testing. An SA/PRA
ratio > or =20 is only interpretable with an SA > or =15 ng/dL and indicates probable primary
aldosteronism. Renal disease, such as unilateral renal artery stenosis, results in elevated renin and
aldosterone levels. Renal venous catheterization may be helpful. A positive test is a renal venous renin
ratio (affected/normal) >1.5. See Renin-Aldosterone Studies and Steroid Pathways in Special
Instructions. Note: Advice on stimulation or suppression tests is available from Mayo Clinic's Division
of Endocrinology and may be obtained by calling Mayo Medical Laboratories.
Reference Values:
No established reference values.
Clinical References: 1. Young WF Jr: Primary aldosteronism: A common and curable form of
hypertension. Cardiol Rev 1999;7:207-214 2. Young WF Jr: Pheochromocytoma and primary
aldosteronism: diagnostic approaches. Endocrinol Metab Clin North Am 1997;26:801-827 3. Hurwitz S,
Cohen RJ, Williams GH: Diurnal variation of aldosterone and plasma renin activity: timing relation to
melatonin and cortisol and consistency after prolonged bed rest. J Appl Physiol 2004;96:1406-1414
Useful For: Investigation of primary aldosteronism (eg, adrenal adenoma/carcinoma and adrenal
cortical hyperplasia) and secondary aldosteronism (renovascular disease, salt depletion, potassium
loading, cardiac failure with ascites, pregnancy, Bartter syndrome)
Interpretation: A high ratio of serum aldosterone (SA) in ng/dL to plasma renin activity (PRA) in
ng/mL per hour, is a positive screening test result, a finding that warrants further testing. An SA/PRA
ratio > or =20 is only interpretable with an SA > or =15 ng/dL and indicates probable primary
aldosteronism. Renal disease, such as unilateral renal artery stenosis, results in elevated renin and
aldosterone levels. Renal venous catheterization may be helpful. A positive test is a renal venous renin
ratio (affected/normal) >1.5. See Renin-Aldosterone Studies and Steroid Pathways in Special
Instructions. Note: Advice on stimulation or suppression tests is available from Mayo Clinic's Division
of Endocrinology and may be obtained by calling Mayo Medical Laboratories.
Reference Values:
No established reference values.
Clinical References: 1. Young WF Jr: Primary aldosteronism: A common and curable form of
hypertension. Cardiol Rev 1999;7:207-214 2. Young WF Jr: Pheochromocytoma and primary
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 75
aldosteronism: diagnostic approaches. Endocrinol Metab Clin North Am 1997;26:801-827 3. Hurwitz S,
Cohen RJ, Williams GH: Diurnal variation of aldosterone and plasma renin activity: timing relation to
melatonin and cortisol and consistency after prolonged bed rest. J Appl Physiol 2004;96:1406-1414
Useful For: Investigation of primary aldosteronism (eg, adrenal adenoma/carcinoma and adrenal
cortical hyperplasia) and secondary aldosteronism (renovascular disease, salt depletion, potassium
loading, cardiac failure with ascites, pregnancy, Bartter syndrome)
Interpretation: A high ratio of serum aldosterone (SA) in ng/dL to plasma renin activity (PRA) in
ng/mL per hour, is a positive screening test result, a finding that warrants further testing. An SA/PRA
ratio > or =20 is only interpretable with an SA > or =15 ng/dL and indicates probable primary
aldosteronism. Renal disease, such as unilateral renal artery stenosis, results in elevated renin and
aldosterone levels. Renal venous catheterization may be helpful. A positive test is a renal venous renin
ratio (affected/normal) >1.5. See Renin-Aldosterone Studies and Steroid Pathways in Special Instructions.
Note: Advice on stimulation or suppression tests is available from Mayo Clinic's Division of
Endocrinology and may be obtained by calling Mayo Medical Laboratories.
Reference Values:
0-30 days: 17-154 ng/dL*
31 days-11 months: 6.5-86 ng/dL*
1-10 years:
< or =40 ng/dL (supine)*
< or =124 ng/dL (upright)*
> or =11 years: < or =21 ng/dL (a.m. peripheral vein specimen)
*Loeuille GA, Racadot A, Vasseur P, Vandewalle B: Blood and urinary aldosterone levels in normal
neonates, infants and children. Pediatrie 1981;36:335-344
Clinical References: 1. Young WF Jr: Primary aldosteronism: A common and curable form of
hypertension. Cardiol Rev 1999;7:207-214 2. Young WF Jr: Pheochromocytoma and primary
aldosteronism: diagnostic approaches. Endocrinol Metab Clin North Am 1997;26:801-827 3. Hurwitz S,
Cohen RJ, Williams GH: Diurnal variation of aldosterone and plasma renin activity: timing relation to
melatonin and cortisol and consistency after prolonged bed rest. J Appl Physiol 2004;96:1406-1414
Reference Values:
<0.35 kU/L
Order MPCT / Muscle Pathology Consultation or MBCT / Muscle Biopsy Consultation, Outside
Slides and/or Paraffin Blocks. The consultant will determine the need for special stains.
Useful For: Detection of rearrangements involving the ALK gene region at 2p23 in patients with
non-small cell lung carcinoma who may benefit from treatment with the ALK inhibitor drugs, like
Xalkori (Crizotinib), on previously stained routine cytology slides
Clinical References: 1. Soda M, Choi YL, Enomoto M, et al: Identification of the transforming
EML4-ALK fusion gene in non-small-cell lung cancer. Nature 2007;448:561-566 2. Betz BL, Dixon
CA, et al: The use of stained cytologic direct smears for ALK gene rearrangement analysis of lung
adenocarcinoma. Cancer Cytopathology 2013;121(9):489-499 3. Minca EC, Lanigan CP, et al: ALK
Status Testing in NonSmall-Cell Lung Carcinoma by FISH on ThinPrep Slides with Cytology
Material. J Thor Oncol 2014;9(4):464-468 4. Rosenblum F, Hutchinson LM, et al: Cytology specimens
offer an effective alternative to formalin-fixed tissue as demonstrated by novel automated detection for
ALK break-apart FISH testing and immunohistochemistry in lung adenocarcinoma. Cancer
Cytopathology 2014;122(11):810-821 5. Salido M, Pijuan L, et al: Increased ALK Gene Copy Number
and Amplification are Frequent in Non-small Cell Lung Cancer. J Thor Oncol 2011;6(1):21-27
Reference Values:
Males
4 years: 149-369 U/L
5 years: 179-416 U/L
6 years: 179-417 U/L
7 years: 172-405 U/L
8 years: 169-401 U/L
9 years: 175-411 U/L
10 years: 191-435 U/L
11 years: 185-507 U/L
12 years: 185-562 U/L
13 years: 182-587 U/L
14 years: 166-571 U/L
15 years: 138-511 U/L
16 years: 102-417 U/L
17 years: 69-311 U/L
18 years: 52-222 U/L
> or =19 years: 45-115 U/L
Females
4 years: 169-372 U/L
5 years: 162-355 U/L
6 years: 169-370 U/L
7 years: 183-402 U/L
8 years: 199-440 U/L
9 years: 212-468 U/L
10 years: 215-476 U/L
11 years: 178-526 U/L
12 years: 133-485 U/L
13 years: 120-449 U/L
14 years: 153-362 U/L
15 years: 75-274 U/L
16 years: 61-264 U/L
17-23 years: 52-144 U/L
24-45 years: 37-98 U/L
46-50 years: 39-100 U/L
51-55 years: 41-108 U/L
56-60 years: 46-118 U/L
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 78
61-65 years: 50-130 U/L
> or =66 years: 55-142 U/L
Reference values have not been established for patients that are <4 years of age.
Clinical References: Tietz NW: Textbook of Clinical Chemistry. Third edition, Edited by Burtis
and Ashwood. Philadelphia, PA, WB Saunders Company, Philadelphia, 1999.
Useful For: Diagnosis and treatment of liver, bone, intestinal, and parathyroid diseases Determining
the tissue source of increased alkaline phosphatase (ALP) activity in serum Differentiating between
liver and bone sources of elevated ALP
Interpretation: Total Alkaline Phosphatase (ALP): ALP elevations tend to be more marked (more
than 3-fold) in extrahepatic biliary obstructions (eg, by stone or cancer of the head of the pancreas) than
in intrahepatic obstructions, and the more complete the obstruction, the greater the elevation. With
obstruction, serum ALP activities may reach 10 to 12 times the upper limit of normal, returning to
normal upon surgical removal of the obstruction. The ALP response to cholestatic liver disease is
similar to the response of gamma-glutamyltransferase (GGT), but more blunted. If both GGT and ALP
are elevated, a liver source of the ALP is likely. Among bone diseases, the highest level of ALP activity
is encountered in Paget's disease, as a result of the action of the osteoblastic cells as they try to rebuild
bone that is being resorbed by the uncontrolled activity of osteoclasts. Values from 10 to 25 times the
upper limit of normal are not unusual. Only moderate rises are observed in osteomalacia, while levels
are generally normal in osteoporosis. In rickets, levels 2 to 4 times normal may be observed. Primary
and secondary hyperparathyroidism are associated with slight to moderate elevations of ALP; the
existence and degree of elevation reflects the presence and extent of skeletal involvement. Very high
enzyme levels are present in patients with osteogenic bone cancer. A considerable rise in ALP is seen in
children following accelerated bone growth. ALP increases of 2 to 3 times normal may be observed in
women in the third trimester of pregnancy, although the reference interval is very wide and levels may
not exceed the upper limit of normal in some cases. In pregnancy, the additional enzyme is of placental
origin. ALP Isoenzymes: Liver ALP isoenzyme is associated with biliary epithelium and is elevated in
cholestatic processes. Various liver diseases (primary or secondary cancer, biliary obstruction) increase
the liver isoenzyme. Liver 1 (L1) is increased in some non-malignant diseases (such as cholestasis,
cirrhosis, viral hepatitis and in various biliary and hepatic pathologies). It is also increased in
malignancies with hepatic metastasis, in cancer of the lungs and digestive tract and in lymphoma. An
increase of Liver 2 (L2) may occur in cholestasis and biliary diseases (eg, cirrhosis, viral hepatitis) and
in malignancies (eg, breast, liver, lung, prostate, digestive tract) with liver metastasis. Osteoblastic bone
tumors and hyperactivity of osteoblasts involved in bone remodeling (eg, Paget's disease) increase the
bone isoenzyme. Paget's disease leads to a striking, solitary elevation of bone ALP. The intestinal
isoenzyme may be increased in patients with cirrhosis and in individuals who are blood group O or B
secretors. The placental (carcinoplacental antigen) and Regan isoenzyme can be elevated in cancer
patients.
Reference Values:
ALKALINE PHOSPHATASE
Males
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4 years: 149-369 U/L
5 years: 179-416 U/L
6 years: 179-417 U/L
7 years: 172-405 U/L
8 years: 169-401 U/L
9 years: 175-411 U/L
10 years: 191-435 U/L
11 years: 185-507 U/L
12 years: 185-562 U/L
13 years: 182-587 U/L
14 years: 166-571 U/L
15 years: 138-511 U/L
16 years: 102-417 U/L
17 years: 69-311 U/L
18 years: 52-222 U/L
> or =19 years: 45-115 U/L
Females
4 years: 169-372 U/L
5 years: 162-355 U/L
6 years: 169-370 U/L
7 years: 183-402 U/L
8 years: 199-440 U/L
9 years: 212-468 U/L
10 years: 215-476 U/L
11 years: 178-526 U/L
12 years: 133-485 U/L
13 years: 120-449 U/L
14 years: 153-362 U/L
15 years: 75-274 U/L
16 years: 61-264 U/L
17-23 years: 52-144 U/L
24-45 years: 37-98 U/L
46-50 years: 39-100 U/L
51-55 years: 41-108 U/L
56-60 years: 46-118 U/L
61-65 years: 50-130 U/L
> or =66 years: 55-142 U/L
Reference values have not been established for patients who are <4 years of age.
Clinical References: 1. Tietz NW: Textbook of Clinical Chemistry, Third edition. Edited by CA
Burtis, ER Ashwood. Philadelphia, PA, WB Saunders Company, 1999 2. Moss DW: Alkaline
phosphatase isoenzymes. Clin Chem 1982;28:2007-2016 3. Teitelbaum JE, Laskowski A, Barrows FP:
Benign transient hyperphosphatasemia in infants and children: a prospective cohort. J Pediatr
Endocrinol Metab 2011;24:351-353 4. Jassam NJ, Horner J, Marzo-Ortega H, et al: Transient rise in
alkaline phosphatase activity in adults. BMJ Case Rep 2009;2009: bcr09.2009.2250. PMC3028401,
Published online Dec 3, 2009
Reference Values:
Immunoglobulin E (IgE)
Age Related Reference Range
1-11 months 0-12
1 year 0-15
2 year 1-29
3 year 4-35
4 year 2-33
5 year 8-56
6 year 3-95
7 year 2-88
8 year 5-71
9 year 3-88
10 year 7-110
11-14 year 7-111
15-19 year 6-96
20-30 year 4-59
31-50 year 5-79
51-80 year 3-48
The gel diffusion method was used to test this patients serum for the presence of precipitating
antibodies (IgG) to the antigens indicated. These antibodies are serological markers for exposure and
immunological sensitization. The clinical significance varies, depending on the history and symptoms.
This test was developed and its performance characteristics determined by Viracor Eurofins. It has not
been cleared or approved by the FDA.
Patients with allergic bronchopulmonary aspergillosis (ABPA) are expected to have the following
serological features:
Useful For: Evaluation of newborn screening specimens that test positive for branched-chain amino
acids elevations Follow-up of patients with maple-syrup urine disease
Reference Values:
Allo-isoleucine: <2 nmol/mL
Leucine: 35-215 nmol/mL
Isoleucine: 13-130 nmol/mL
Valine: 51-325 nmol/mL
An interpretive report will also be provided.
Clinical References: 1. Chace DH, Kalas TA, Naylor EW: Use of tandem mass spectrometry for
multianalyte screening of dried blood specimens from newborns. Clin Chem 2003;49(11):1797-1817 2.
Simon E, Fingerhut R, Baumkotter J, et al: Maple syrup urine disease: Favorable effect of early
diagnosis by newborn screening on the neonatal course of the disease. J Inherit Metab Dis
2006;29:532-537 3. Morton DH, Strauss KA, Robinson DL, et al: Diagnosis and treatment of maple
syrup disease: a study of 36 patients. Pediatrics 2002;109:999-1008 4. Oglesbee D, Sanders KA, Lacey
JM, et al: Second-tier test for quantification of alloisoleucine and branched-chain amino acids in dried
blood spots to improve newborn screening for maple syrup urine disease (MSUD). Clin Chem 2008
Mar;54(3):542-549 5. Strauss KA, Puffenberger EG, Morton DH: Maple Syrup Urine Disease. Updated
2013 May 9. Edited by RA Pagon, MP Adam, HH Ardinger. University of Washington, Seattle,
1993-2016. Available at http://www.ncbi.nlm.nih.gov/books/NBK1319
Reference Values:
<2 mcg/mL
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical
utility of food-specific IgG tests has not been established. These tests can be used in special clinical
situations to select foods for evaluation by diet elimination and challenge in patients who have
food-related complaints. It should be recognized that the presence of food-specific IgG alone cannot be
taken as evidence of food allergy and only indicates immunologic sensitization by the food allergen in
question. This test should only be ordered by physicians who recognize the limitations of the test.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 83
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
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Useful For: Diagnosing autoimmune lymphoproliferative syndrome, primarily in patients <45 years
of age
Interpretation: The presence of increased circulating T cells (CD3+) that are negative for CD4 and
CD8 (double-negative T cells: DNT) and positive for the alpha/beta T-cell receptor (TCR) is required
for the diagnosis of autoimmune lymphoproliferative syndrome (ALPS). The laboratory finding of
increased alpha beta TCR+DNT cells is consistent with ALPS only with the appropriate clinical picture
(nonmalignant lymphadenopathy, splenomegaly, and autoimmune cytopenias). Conversely, there are
other immunological disorders, including common variable immunodeficiency (CVID), which have
subsets for patients with this clinical picture, but no increase in alpha beta TCR+DNT cells. If the
percent of the absolute count of either the alpha beta TCR+DNT cells or alpha beta TCR+DNT B220+
cells is abnormal, additional testing is indicated. All abnormal alpha beta TCR+DNT cell results should
be confirmed (for ALPS) with additional testing for defective in vitro lymphocyte apoptosis, followed
by confirmatory genetic testing for FAS mutations (contact Mayo Medical Laboratories for test
forwarding information).
Reference Values:
Alpha beta TCR+DNT cells
2-18 years: <2% CD3 T cells
19-70+ years: <3% CD3 T cells
Reference values have not been established for patients that are less than 24 months of age.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 85
in persons from any ethnic group. Four alpha globin genes are normally present, 2 copies on each
chromosome 16. Alpha thalassemia mutations result in decreased alpha globin chain production. In
general, alpha thalassemia is characterized by hypochromic, microcytic anemia and varies clinically
from asymptomatic (alpha thalassemia silent carrier and alpha thalassemia trait) to lethal hemolytic
anemia (hemoglobin: Hb Barts hydrops fetalis). Large deletions of the alpha globin genes account for
approximately 90% of alpha thalassemia mutations, and these mutations will not be detected by alpha
globin gene sequencing. Other mutations, such as point mutations or small deletions within the alpha
globin genes, account for most of the remaining 10% of alpha thalassemia mutations. These
nondeletional subtypes can be detected by alpha globin gene sequencing. The most common
nondeletional alpha thalassemia mutation is Hb Constant Spring (Hb CS). The majority of alpha globin
chain variants are clinically and hematologically benign; however some cause erythrocytosis and
chronic hemolytic anemia. Hemoglobin electrophoresis may not be able to confirm their identity. In
these instances alpha globin gene sequencing can be useful.
Useful For: Diagnosing nondeletional alpha thalassemia Testing for nondeletional alpha thalassemia in
a symptomatic individual Follow-up testing to an abnormal hemoglobin electrophoresis that identified an
alpha globin chain variant
Clinical References: 1. Harteveld CL, Higgs DR: Alpha-thalassemia. Orphanet J Rare Dis
2010;5:13 2. Hoyer JD, Hoffman DR: The Thalassemia and hemoglobinopathy syndromes. In Clinical
Laboratory Medicine. Second edition. Edited by KD McMlatchey. Philadelphia, Lippincott Williams and
Wilkins. 2002, pp 866-895
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical utility
of food-specific IgG tests has not been established. These tests can be used in special clinical situations to
select foods for evaluation by diet elimination and challenge in patients who have food-related
complaints. It should be recognized that the presence of food-specific IgG alone cannot be taken as
evidence of food allergy and only indicates immunologic sensitization by the food allergen in question.
This test should only be ordered by physicians who recognize the limitations of the test.
Clinical References: 1. Callea F, Fevery J, Massi G, et al: Alpha-1-antitrypsin (AAT) and its
stimulation in the liver of PiMZ phenotype individuals. A "recruitment-secretory block" ("R-SB")
phenomenon. Liver 1984:4(5):325-337 2. Lam M, Torbenson M, Yeh MM, et al: HFE mutations in
alpha-1-antitrypsin deficiency: an examination of cirrhotic explants. Mod Pathol 2010;23:637-643 3.
Theaker JM, Fleming KA: Alpha-1-antitrypsin and the liver: a routine immunohistological screen. J
Clin Pathol 1986;39(1):58-62
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Reference Values:
Clearance: < or =27 mL/24 hours
Fecal alpha-1-antitrypsin concentration: < or =54 mg/dL
Serum alpha-1-antitrypsin concentration: 100-190 mg/dL
Interpretation: There are >40 alpha-1-antitrypsin (A1A) phenotypes (most of these are associated
with normal quantitative levels of protein). The most common normal phenotype is M (M, M1, or M2),
and >90% of Caucasians are genetically homozygous M (MM). A1A deficiency is usually associated with
the Z phenotype (homozygous ZZ), but SS and SZ are also associated with decreased A1A levels.
Reference Values:
ALPHA-1-ANTITRYPSIN
100-190 mg/dL
ALPHA-1-ANTITRYPSIN PHENOTYPE
The interpretive report will identify the alleles present. For rare alleles, the report will indicate whether
or not they have been associated with reduced quantitative levels of alpha-1-antitrypsin.
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occurs much less commonly than emphysema in adults. A1A deficiency is a relatively common disorder
in Northern European Caucasians. The diagnosis of A1A deficiency is initially made by quantitation of
protein levels in serum followed by determination of specific allelic variants by isoelectric focusing (IEF).
While there are many different alleles in this gene, only 3 are common. The 3 major alleles include: M
(full functioning, normal allele), S (associated with reduced levels of protein), and Z (disease-causing
mutation associated with liver disease and premature emphysema). The S and Z alleles account for the
majority of the abnormal alleles detected in affected patients. As a codominant disorder, both alleles are
expressed. An individual of SZ or S-null genotype may have a small increased risk for emphysema (but
not liver disease) due to slightly reduced protein levels. On the other hand, an individual with the ZZ
genotype is at greater risk for early onset liver disease and premature emphysema. Smoking appears to
hasten development of emphysema by 10 to 15 years. These individuals should be monitored closely for
lung and liver function. Historically, IEF has been the primary method for characterizing variants, though
in some cases the interpretation is difficult and prone to error. Serum quantitation is helpful in
establishing a diagnosis, but can be influenced by other factors. A proteomic method using
trypsin-digested sera can detect the mutated peptides of the S and Z alleles, but can miss disease alleles
other than the S and Z alleles. This test combines all of these methods to provide a comprehensive result.
Useful For: Determining the specific proteotype for prognosis and genetic counseling for patients
with alpha-1-antitrypsin deficiency
Interpretation: For each of the possible alpha-1-antitrypsin (A1A) genotypes there is an expected
range for the total serum level of A1A. However, a number of factors can influence either the A1A
serum level or the A1A proteotype results, including acute illness (A1A is an acute-phase reactant),
protein replacement therapy, the presence of other rare variants, or the presence of DNA
polymorphisms. When the serum level differs from what is expected for that proteotype (ie, discordant),
additional studies are performed to ensure the most appropriate interpretation of test results. Additional
follow-up may include A1A phenotyping by isoelectric focusing, obtaining additional clinical
information, and DNA sequencing. See Alpha-1-Antitrypsin Reflex Table in Special Instructions.
Reference Values:
ALPHA-1-ANTITRYPSIN
100-190 mg/dL
ALPHA-1-ANTITRYPSIN PROTEOTYPE
Negative for S and Z phenotype (Non S Non Z)
Useful For: Diagnosing protein-losing enteropathies, especially when used in conjunction with
serum alpha-1-antitrypsin (A1A) levels as a part of A1A clearance studies (see CA1A /
Alpha-1-Antitrypsin Clearance, Feces and Serum; preferred test)
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Reference Values:
< or =54 mg/dL
Useful For: Workup of individuals with suspected disorders such as familial chronic obstructive lung
disease Diagnosis of alpha-1-antitrypsin deficiency
Interpretation: Patients with serum levels <70 mg/dL may have a homozygous deficiency and are at
risk for early lung disease. Alpha-1-antitrypsin proteotyping should be done to confirm the presence of
homozygous deficiency alleles. If clinically indicated, patients with serum levels <125 mg/dL should be
proteotyped in order to identify heterozygous individuals. Heterozygotes do not appear to be at increased
risk for early emphysema.
Reference Values:
100-190 mg/dL
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Useful For: Assessment of renal tubular injury or dysfunction Screening for tubular abnormalities
Detecting chronic asymptomatic renal tubular dysfunction(2)
Reference Values:
> or =16 years: <19 mg/24 hours
7 mg/g creatinine is a literature suggested upper reference limit for pediatrics 1 month to 15 years of
age.*
*Hjorth L, Helin I, Grubb A: Age-related reference limits for protein HC in children. Scand J Clin Lab
Invest 2000 Feb;60(1):65-73
Useful For: Assessment of renal tubular injury or dysfunction Screening for tubular abnormalities
Detecting chronic asymptomatic renal tubular dysfunction
Interpretation: Alpha-1-microglobulin above the reference values may indicate a proximal tubular
dysfunction. As suggested in the literature, 7 mg/g creatinine is an upper reference limit for pediatric
patients of 1 month to 15 years of age.
Reference Values:
<50 years: <13 mg/g creatinine
> or =50 years: <20 mg/g creatinine
Useful For: Diagnosing congenital alpha-2 plasmin inhibitor deficiencies (rare) Providing a more
complete assessment of disseminated intravascular coagulation, intravascular coagulation and fibrinolysis,
or hyperfibrinolysis (primary fibrinolysis), when measured in conjunction with fibrinogen, fibrin D-dimer,
fibrin degradation products, soluble fibrin monomer complex, and plasminogen Evaluating liver disease
Evaluating the effects of fibrinolytic or antifibrinolytic therapy
Interpretation: Patients with congenital homozygous deficiency (with levels of <10%) are clinically
affected (bleeding). Heterozygotes having levels of 30% to 60% of mean normal activity are usually
asymptomatic. Lower than normal levels may be suggestive of consumption due to activation of
plasminogen and its inhibition by alpha-2 plasmin inhibitor. The clinical significance of high levels of
alpha-2 plasmin inhibitor is unknown.
Reference Values:
Adults: 80-140%
Normal, full-term newborn infants may have borderline low or mildly decreased levels (> or =50%)
which reach adult levels within 5 to 7 days postnatal.*
Healthy, premature infants (30-36 weeks gestation) may have mildly decreased levels which reach adult
levels in < or =90 days postnatal.*
*See Pediatric Hemostasis References in Coagulation Studies in Special Instructions.
Clinical References: 1. Lijnen HR, Collen D: Congenital and acquired deficiencies of components
of the fibrinolytic system and their relation to bleeding or thrombosis. Blood Coagul Fibrinolysis
1989;3:67-77 2. Francis RB Jr: Clinical disorders of fibrinolysis: A critical review. Blut 1989;59:1-14 3.
Aoki N: Hemostasis associated with abnormalities of fibrinolysis. Blood Rev 1989;3:11-17
Reference Values:
100-280 mg/dL
Clinical References: 1. McMahon MJ, Bowen M, Mayer AD, Cooper EH: Relation of
alpha-2-macroglobulin and other antiproteases to the clinical features of acute pancreatitis. Am J Surg
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 92
1984;147:164-170 2. Haines AP, Howarth D, North WR, et al: Haemostatic variables and the outcome of
myocardial infarction. Thromb Haemost 1983;50:800-803 3. Hofmann W, Schmidt D, Guder WG, Edel
HH: Differentiation of hematuria by quantitative determination of urinary marker proteins. Klin
Wochenschr 1991;69:68-75 4. Solerte SB, Adamo S, Viola C, et al: Acute-phase protein reactants pattern
and alpha 2 macroglobulin in diabetes mellitus. Pathophysiological aspects in diabetic microangiopathy.
La RIC Clin Lab 1994;14:575-579 5. Silverman LM, Christenson RH, Grant GH: Basic chemistry of
amino acids and proteins. In Clinical Guide to Laboratory Tests. Second edition. Edited by NW Tietz.
Philadelphia, WB Saunders Company, 1990, pp 380-381
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Clinical References: 1. Romi F, Helgeland G, Gilhus NE: Heat-shock proteins in clinical neurology.
Eur Neurol 2011;66(2):65-69 2. Fort PE, Lampi KJ: New focus on alpha-crystallins in retinal
neurodegenerative diseases. Exp Eye Res 2011 Feb;92(2):98-103 3. Pinder SE, Balsitis M, Ellis IO, et al:
The expression of alpha B-crystallin in epithelial tumours: a useful tumour marker? J Pathol 1994
Nov;174(3):209-215 4. Leach IH, Tsang ML, Church RJ, Lowe J: Alpha-B crystallin in the normal
human myocardium and cardiac conducting system. J Pathol 1994 Jul;173(3):255-260 5. Lowe J,
McDermott H, Pike I, et al: alpha B crystallin expression in non-lenticular tissues and selective presence
in ubiquitinated inclusion bodies in human disease. J Pathol 1992 Jan;166(1):61-68 6. Iwaki T,
Wisniewski T, Iwaki A, et al: Accumulation of alpha B-crystallin in central nervous system glia and
neurons in pathologic conditions. Am J Pathol 1992 Feb;140(2):345-356
Useful For: Distinguishing between hepatocellular carcinoma and chronic liver disease Monitoring
individuals with hepatic cirrhosis from any etiology for progression to hepatocellular carcinoma
Surveillance for development of hepatocellular carcinoma in individuals with a positive family history of
hepatic cancer Surveillance for development of hepatocellular carcinoma in individuals within specific
ethnic and gender groups who do not have hepatic cirrhosis, but have a confirmed diagnosis of chronic
infection by hepatitis B acquired early in life including: -African males above the age of 20 -Asian males
above the age of 40 -Asian females above the age of 50
Interpretation: Alpha-fetoprotein (AFP)-L3 > or =10% is associated with a 7-fold increased risk of
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 94
developing hepatocellular carcinoma. Patients with AFP-L3 > or =10% should be monitored more
intensely for evidence of hepatocellular carcinoma according to current practice guidelines. Total serum
AFP >200 ng/mL is highly suggestive of a diagnosis of hepatocellular carcinoma. In patients with liver
disease, a total serum AFP of >200 ng/mL is near 100% predictive of hepatocellular carcinoma. With
decreasing total AFP levels, there is an increased likelihood that chronic liver disease, rather than
hepatocellular carcinoma, is responsible for the AFP elevation. Based on a retrospective study at the
Mayo Clinic, for patients with total AFP levels < or =200 ng/mL, AFP-L3 specificity approaches 100%
for hepatocellular carcinoma when its percentage exceeds 35% of the total AFP.(4) AFP concentrations
over 100,000 ng/mL have been reported in normal newborns, and the values rapidly decline in the first 6
years of life.
Reference Values:
<10%
Useful For: The follow-up management of patients undergoing cancer therapy, especially for
testicular and ovarian tumors and for hepatocellular carcinoma Often used in conjunction with human
chorionic gonadotropin(2)
Reference Values:
<6.0 ng/mL
Reference values are for nonpregnant subjects only; fetal production of AFP elevates values in
pregnant women.
Range for newborns is not available, but concentrations over 100,000 ng/mL have been reported in
normal newborns, and the values rapidly decline in the first 6 months of life.(See literature reference:
Ped Res 1981;15:50-52) For further interpretive information, see Alpha-Fetoprotein (AFP) in Special
Instructions.
Serum markers are not specific for malignancy, and values may vary by method.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 95
Clinical References: 1. Sturgeon CM, Duffy MJ, Stenman UH, et al: National Academy of Clinical
Biochemistry laboratory medicine practice guidelines for use of tumor markers in testicular, prostate,
colorectal, breast, and ovarian cancers. Clin Chem 2008 Dec; 54(12):e11-79 2. Blohm ME,
Vesterling-Horner D, Calaminus G, et al: Alpha-1-fetoprotein (AFP) reference values in infants up to 2
years of age. Pediatr Hematol Onco 1998 Mar-April;15(2):135-142 3. Milose JC, Filson CP, Weizer AZ,
et al: Role of biochemical markers in testicular cancer: diagnosis, staging, and surveillance. Open Access
J Urol 2011 Dec 30;4:1-8 4. Schefer H, Mattmann S, Joss RA: Hereditary persistence of
alpha-fetoprotein. Case report and review of the literature. Ann Oncol 1998 June;9(6):667-672
Useful For: An aid in the identification of yolk sac tumors and hepatocellular carcinoma
Interpretation: This test includes only technical performance of the stain (no pathologist interpretation
is performed). If diagnostic consultation by a pathologist is required, order 70012 / Pathology
Consultation. The positive and negative controls are verified as showing appropriate immunoreactivity. If
a control tissue is not included on the slide, a scanned image of the relevant quality control tissue is
available upon request; contact 855-516-8404. Interpretation of this test should be performed in the
context of the patient's clinical history and other diagnostic tests by a qualified pathologist.
Clinical References: 1. Porcell AI, De Young BR, Proca DM, Frankel WL: Immunohistochemical
analysis of hepatocellular and adenocarcinoma in the liver: MOC31 compares favorably with other
putative markers. Mod Pathol 2000;13(7):773-778 2. Suzuki A, Koide N, Kitazawa M, et al: Gastric
composite tumor of alpha fetoprotein-producing carcinoma/hepatoid adenocarcinoma and endocrine
carcinoma with reference to cellular phenotypes. Patholog Res Int 2012;2012:1-8 3. Tsung SH: The
Characteristics of Immunoreactivity of Alpha-fetoprotein Producing Gastric Cancer. Cancer and Clinical
Oncology 2013;2(1):73-79
Useful For: An adjunct to cytology to differentiate between malignancy-related ascites and benign
causes of ascites formation
Interpretation: A peritoneal fluid alpha-fetoprotein (AFP) concentration >6.0 ng/mL is suspicious but
not diagnostic of ascites related to hepatocellular carcinoma (HCC). This clinical decision limit cutoff
yielded a sensitivity of 58%, specificity of 96% in a study of 137 patients presenting with ascites. AFP
concentrations were significantly higher in ascites caused by HCC. Ascites caused by malignancies other
than HCC routinely had AFP concentrations <6.0 ng/mL. Therefore, negative results should be interpreted
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 96
with caution.
Reference Values:
An interpretive report will be provided.
Clinical References: Sari R, Yildirim B, Sevinc A, et al: The importance of serum and ascites
fluid alpha-fetoprotein, carcinoembryonic antigen, CA 19-9, and CA 15-3 levels in differential
diagnosis of ascites etiology. Hepatogastroenterology 2001 Nov-Dec;48(42):1616-1621
Reference Values:
NEURAL TUBE DEFECTS
An AFP multiple of the median (MoM) <2.5 is reported as screen negative. AFP MoMs > or =2.5
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 97
(singleton and twin pregnancies) are reported as screen positive.
Clinical References: Christensen RL, Rea MR, Kessler G, et al: Implementation of a screening
program for diagnosing open neural tube defects: selection, evaluation, and utilization of
alpha-fetoprotein methodology. Clin Chem 1986;32:1812-1817
Useful For: An adjunct in the diagnosis of central nervous system (CNS) germinomas and meningeal
carcinomatosis Evaluating germ-cell tumors, including testicular cancer metastatic to the CNS in
conjunction with beta-human chorionic gonadotropin measurement(1) An adjunct in distinguishing
between suprasellar dysgerminomas and craniopharyngiomas A supplement to cerebrospinal fluid
cytologic analysis
Interpretation: Alpha-fetoprotein (AFP) concentrations that exceed the upper end of normal are
consistent with the presence of central nervous system germinoma, meningeal carcinomatosis, or
metastatic nonseminomatous testicular cancer. AFP is not elevated in the presence of a
craniopharyngioma.
Reference Values:
<1.5 ng/mL
Values for alpha-fetoprotein in cerebrospinal fluid have not been formally established for newborns and
infants. The available literature indicates that by 2 months of age, levels comparable to adults should be
reached.(Ann Clin Biochem 2005;42:24-29)
Clinical References: 1. Jubran RF, Finlay J: Central nervous system germ cell tumors: controversies
in diagnosis and treatment. Oncology 2005;19:705-711 2. Seregni E, Massimino M, Nerini Molteni S, et
al: Serum and cerebrospinal fluid human chorionic gonadotropin (hCG) and alpha-fetoprotein (AFP) in
intracranial germ cell tumors. Int J Biol Markers 2002;17(2):112-118 3. Coakley J, Kellie SJ:
Interpretation of alpha-fetoprotein concentrations in cerebrospinal fluid of infants. Ann Clin Biochem
2005;42:24-29
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 98
Useful For: Screening for open neural tube defects or other fetal abnormalities Follow-up testing for
patients with elevated serum alpha-fetoprotein results or in conjunction with cytogenetic testing
Reference Values:
< or =2.0 multiples of median (MoM)
Clinical References: Assessing the Quality of Systems for Alpha-Fetoprotein (AFP) Assays Used
in Prenatal Screening and Diagnosis of Open Neural Tube Defects: Approved Guideline. NCCLS
I/LA17-A Vol 17. No 5. April 1997
Reference Values:
> or =0.41 nmol/min/mg protein
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 99
Division, 2009, pp 747-748 3. Thomas GH. Disorders of Glycoprotein Degradation:
Alpha-Mannosidosis, Beta-Mannosidosis, Fucosidosis, and Sialidosis. Edited by Valle D, Beaudet AL,
Vogelstein B, et al. New York, NY: McGraw-Hill; 2014. . Accessed April 20, 2015. Available at:
http://ommbid.mhmedical.com/content.aspx?bookid=971&Sectionid=62642875 4. Barlow JJ,
DiCioccio RA, Dillard PH, et al: Frequency of an allele for low activity of alpha-L-fucosidase in sera:
possible increase in epithelial ovarian cancer patients. J Natl Cancer Inst 1981 Nov;67(5):1005-1009
Reference Values:
Beef IgE <0.35 kU/L
Lamb/Mutton IgE <0.35 kU/L
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 100
Pork IgE <0.35 kU/L
Galactose-alpha-1,3-galactose (Alph Gal) IgE* <0.35 kU/L
Previous reports (JACI 2009; 123:426-433) have demonstrated that patients with IgE antibodies to
galactose-a-1, 3-galactose are at risk for delayed anaphylaxis, angioedema, or urticaria following
consumption of beef, pork, or lamb.
* This test was developed and its performance characteristics determined by Viracor Eurofins. It has not
been cleared or approved by the FDA.
Useful For: Evaluation of patients with a clinical presentation suggestive of Fabry disease Follow-up
to an abnormal newborn screen for Fabry disease
Interpretation: In male patients, results less than 1.2 nmol/mL/hour in properly submitted
specimens are consistent with Fabry disease. Normal results (> or =1.2 nmol/mL/hour) are not
consistent with Fabry disease. In female patients, normal results (> or =2.8 nmol/mL/hour) in properly
submitted specimens are typically not consistent with carrier status for Fabry disease; however, enzyme
analysis, in general, is not sufficiently sensitive to detect all carriers. Because a carrier range has not
been established in females, molecular genetic analysis of the GLA gene (FABRZ / Fabry Disease, Full
Gene Analysis) should be considered when alpha-galactosidase A activity is less than 2.9
nmol/mL/hour, or if clinically indicated. Pseudodeficiency results in low measured alpha-galactosidase
A, but is not consistent with Fabry disease; FABRZ / Fabry Disease, Full Gene Analysis should be
performed to resolve the clinical question. See Fabry Disease Testing Algorithm in Special Instructions.
Reference Values:
Males: > or =1.2 nmol/mL/hour
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 101
Females: > or =2.8 nmol/mL/hour
An interpretive report will be provided.
Clinical References: 1. Chamoles NA, Blanco M, Gaggioli D: Fabry disease: enzymatic diagnosis
in dried blood spots on filter paper. Clin Chim Acta 2001;308:195-196 2. De Schoenmakere G, Poppe B,
Wuyts B, et al: Two-tier approach for the detection of alpha-galactosidase A deficiency in kidney
transplant recipients. Nephrol Dial Transplant 2008;23:4044-4048 3. Spada M, Pagliardini S, Yasuda M,
et al: High incidence of later-onset Fabry disease revealed by newborn screening. Am J Hum Genet
2006;79:31-40 4. Matern D, Gavrilov D, Oglesbee D, et al: Newborn screening for lysosomal storage
disorders. Semin Perinatol 2015 Apr;39(3):206-216 5. Mehta A, Hughes DA: Fabry Disease. In
GeneReviews. Accessed 1/23/2017. Available atwww.ncbi.nlm.nih.gov/books/NBK1292/
Useful For: Diagnosis of Fabry disease in males Verifying abnormal serum alpha-galactosidase results
in males with a clinical presentation suggestive of Fabry disease
Reference Values:
> or =23.1 nmol/hour/mg protein
An interpretative report will be provided.
Note: Results from this assay do not reflect carrier status because of individual variation of
alpha-galactosidase enzyme levels.
Clinical References: 1. Desnick RJ, Ioannou YA, Eng CM: Chapter 150: Alpha-galactosidase A
deficiency: Fabry disease. In The Metabolic Basis of Inherited Disease. Eighth edition. Edited by D Valle,
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 102
AL Beaudet, B Vogelstein. New York, McGraw-Hill Book Company. Available at www.ommbid.com.
Accessed 01/23/15 2. De Schoenmakere G, Poppe B, Wuyts B, et al: Two-tier approach for the detection
of alpha-galactosidase A deficiency in kidney transplant recipients. Nephrol Dial Transplant
2008;23:4044-4048 3. Mehta A, Hughes DA: Fabry Disease. In GeneReviews. 2002 Aug 5, Updated 2013
Oct 17. Edited by RA Pagon, MP Adam, HH Ardinger, et al: Seattle, WA. University of Washington,
Seattle; 1993-2015. Available at www.ncbi.nlm.nih.gov/books/NBK1292/. Accessed 1/23/15 4. Laney
DA, Bennett RL, Clarke V, et al: Fabry disease practice guidelines: recommendations of the National
Society of Genetic Counselors. J Genet Couns 2013;22:555-564 5. Laney DA, Peck DS, Atherton AM, et
al: Fabry disease in infancy and early childhood: a systematic literature review. Genet Med 2014; Epub
ahead of print. Available at www.nature.com/gim/journal/vaop/ncurrent/pdf/gim2014120a.pdf. Accessed
1/23/15
Useful For: Diagnosis of Fabry disease in males Serum testing is the preferred screen for Fabry
disease
Reference Values:
0.074-0.457 U/L
Note: Results from this assay are not useful for carrier determination. Carriers usually have levels in
the normal range.
Clinical References: 1. Desnick RJ, Ioannou YA, Eng CM: Chapter 150: Alpha-galactosidase A
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 103
deficiency: Fabry disease. In The Metabolic Basis of Inherited Disease. Eighth edition. Edited by D
Valle, AL Beaudet, B Vogelstein. New York, McGraw-Hill Book Company. Available at
www.ommbid.com. Accessed 01/23/15 2. De Schoenmakere G, Poppe B, Wuyts B, et al: Two-tier
approach for the detection of alpha-galactosidase A deficiency in kidney transplant recipients. Nephrol
Dial Transplant 2008;23:4044-4048 3. Mehta A, Hughes DA: Fabry Disease. In GeneReviews. 2002
Aug 5, Updated 2013 Oct 17. Edited by RA Pagon, MP Adam, HH Ardinger, et al: Seattle, WA.
University of Washington, Seattle; 1993-2015. Available at www.ncbi.nlm.nih.gov/books/NBK1292/.
Accessed 1/23/15 4. Laney DA, Bennett RL, Clarke V, et al: Fabry disease practice guidelines:
recommendations of the National Society of Genetic Counselors. J Genet Couns 2013;22:555564 5.
Laney DA, Peck DS, Atherton AM, et al: Fabry disease in infancy and early childhood: a systematic
literature review. Genet Med 2014;Epub ahead of print. Available at
www.nature.com/gim/journal/vaop/ncurrent/pdf/gim2014120a.pdf. Accessed 1/23/15
Order MPCT / Muscle Pathology Consultation or MBCT / Muscle Biopsy Consultation Outside Slides
and/or Paraffin Blocks. The consultant will determine the need for special stains.
Interpretation: Specimens with results below 1.0 nmol/hour/mL in properly submitted specimens
are consistent with alpha-L-iduronidase deficiency (mucopolysaccharidosis I). Further differentiation
between Hurler, Scheie, and Hurler-Scheie is dependent upon the clinical findings. Normal results (> or
=1.0 nmol/h/mL) are not consistent with alpha-L-iduronidase deficiency.
Reference Values:
> or =1.0 nmol/hour/mL
An interpretive report will be provided.
Clinical References: 1. Neufeld EF, Muenzer J: The mucopolysaccharidoses. Chapter 136. In The
Metabolic Basis of Inherited Disease. Eighth edition. Edited by D Valle, AL Beaudet, B Vogelstein.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 105
New York, McGraw-Hill Book Company. Accessed 1/25/2017. Available at: www.ommbid.com 2.
Chamoles NA, Blanco M, Gaggioli D, Casentini C: Hurler-like phenotype: enzymatic diagnosis in dried
blood spots on filter paper. Clin Chem 2001;47:2098-2102 3. Martins AM, Dualibi AP, Norato D, et al:
Guidelines for the management of mucopolysaccharidosis type I. J Pediatr 2009 Oct:155(4
Suppl):S32-S46 4. Enns GM, Steiner RD, Cowan TM: Lysosomal disorders: mucopolysaccharidoses. In
Pediatric Endocrinology and Inborn Errors of Metabolism. Edited by K Sarafoglou, GF Hoffmann, KS
Roth. McGraw-Hill, Medical Publishing Division, 2009, pp 721-730 5. Clarke LA.
Mucopolysaccharidosis Type I. In GeneReviews. Edited by RA Pagon, MP Adam, HH Ardinger et al.
University of Washington, Seattle. Updated 2016 Feb 11. 1993-2017. Available at
www.ncbi.nlm.nih.gov/books/NBK1162/
Useful For: Diagnosis of mucopolysaccharidosis I, Hurler, Scheie, and Hurler-Scheie syndromes using
dried blood spot specimens
Interpretation: Specimens with results below 1.0 nmol/hour/mL in properly submitted specimens are
consistent with alpha-L-iduronidase deficiency (mucopolysaccharidosis I). Further differentiation between
Hurler, Scheie, and Hurler-Scheie is dependent on the clinical findings. Normal results (> or =1.0
nmol/hour/mL) are not consistent with alpha-L-iduronidase deficiency.
Reference Values:
> or =1.0 nmol/h/mL
An interpretive report will be provided.
Clinical References: 1. Neufeld EF, Muenzer J: The mucopolysaccharidoses. Chapter 136. In The
Metabolic and Molecular Basis of Inherited Disease. Eighth edition. Edited by D Valle, AL Beaudet, B
Vogelstein. New York, McGraw-Hill Book Company. Accessed 1/25/2017. Available at:
www.ommbid.com 2. Chamoles NA, Blanco M, Gaggioli D, Casentini C: Hurler-like phenotype:
enzymatic diagnosis in dried blood spots on filter paper. Clin Chem 2001;47:2098-2102 3. Martins AM,
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 106
Dualibi AP, Norato D, et al: Guidelines for the management of mucopolysaccharidosis type I. J Pediatr
2009 Oct:155(4 Suppl):S32-S46 4. Enns GM, Steiner RD, Cowan TM: Lysosomal disorders:
mucopolysaccharidoses. In Pediatric Endocrinology and Inborn Errors of Metabolism. Edited by K
Sarafoglou, GF Hoffmann, KS Roth. McGraw-Hill, Medical Publishing Division, 2009, pp 721-730 5.
Clarke LA. Mucopolysaccharidosis Type I. In GeneReviews. Edited by RA Pagon, MP Adam, HH
Ardinger et al. University of Washington, Seattle. Updated 2016 Feb 11. Available at
www.ncbi.nlm.nih.gov/books/NBK1162/
Useful For: Diagnosis of mucopolysaccharidosis I (MPS I), Hurler syndrome (MPS IH), Scheie
syndrome (MPS IS), and Hurler-Scheie syndrome (MPS IH/S) in fibroblasts
Reference Values:
> or =0.87 nmol/min/mg protein
Clinical References: 1. Martins AM, Dualibi AP, Norato D, et al: Guidelines for the management
of mucopolysaccharidosis type I. J Pediatr 2009 Oct:155(4 Suppl):S32-S46 2. Neufeld EF, Muenzer J:
The Mucopolysaccharidoses. In: The Online Metabolic and Molecular Bases of Inherited Disease.
Edited by D Valle, AL Beaudet, B Vogelstein B, et al: New York, NY: McGraw-Hill; 2014. Accessed
May 04, 2015. Available at:
http://ommbid.mhmedical.com/content.aspx?bookid=971&Sectionid=62642135 3. Enns GM, Steiner
RD, Cowan TM: Lysosomal disorders: mucopolysaccharidoses. In Pediatric Endocrinology and Inborn
Errors of Metabolism. Edited by K Sarafoglou, GF Hoffmann, KS Roth. McGraw-Hill, Medical
Publishing Division, 2009, pp 721-730 4. Clarke LA. Mucopolysaccharidosis Type I. 2002 Oct 31
[Updated 2016 Feb 11]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews [Internet].
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 107
Seattle (WA): University of Washington, Seattle; 1993-2016. Accessed February 23, 2016. Available at:
http://www.ncbi.nlm.nih.gov/books/NBK1162/
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 108
respect to age of onset and clinical presentation. Type 1 is generally classified by a mild presentation and
slow progression with onset after 10 years of age and absence of skeletal abnormalities. Type 2 is
generally a more moderate form with slow progression and onset prior to 10 years of age with skeletal
abnormalities and myopathy. Type 3 is the most severe form with onset in early infancy, skeletal
abnormalities (dysostosis multiplex), and severe central nervous system involvement. Although treatment
is mostly supportive and aimed at preventing complications, hematopoietic stem cell transplant (HSCT)
has been reported to be a feasible therapeutic option. The incidence of alpha-mannosidosis is estimated at
1 in 500,000 live births. An initial diagnostic workup for alpha-mannosidosis includes a multienzyme
screening assay for several oligosaccharidoses, including mannosidosis in leukocytes or fibroblasts
(OLIWB / Oligosaccharidoses Screen, Leukocytes or OLITC / Oligosaccharidoses Screen, Fibroblasts). If
the screening assay is suggestive of alpha-mannosidosis, enzyme analysis of acid alpha-mannosidase can
confirm the diagnosis. Sequencing of MAN2B1 allows for detection of disease-causing mutations in
affected patients and identification of familial mutations allows for testing of at-risk family members.
Reference Values:
> or =0.53 nmol/min/mg protein
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 109
alpha-mannosidosis.
Reference Values:
> or =0.54 nmol/min/mg protein
Reference Values:
> or =0.05 nmol/min/mg protein
Clinical References: 1. Heron B, Mikaeloff Y, Froissart R, et al: Incidence and natural history of
mucopolysaccharidosis type III in France and comparison with United Kindgom and Greece. Am J Med
Genet A 2011;155A(1):58-68 2. Neufeld EF, Muenzer J: The Mucopolysaccharidoses. In: The Online
Metabolic and Molecular Bases of Inherited Disease. Edited by D Valle, AL Beaudet, B Vogelstein B, et
al: New York, NY: McGraw-Hill; 2014 Available at
http://ommbid.mhmedical.com/content.aspx?bookid=971&Sectionid=62642135. Accessed May 04, 2015
3. Valstar MJ, Bruggenwirth HT, Olmer R, et al: Mucopolysaccharidosis type IIIB may predominantly
present with an attenuated clinical phenotype. J Inherit Metab Dis 2010;33:759-767
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 110
sulfate, keratan sulfate, or chondroitin sulfate (glycosaminoglycans GAG). Accumulation of GAG in
lysosomes interferes with normal functioning of cells, tissues, and organs resulting in the clinical features
observed in MPS disorders. Sanfilippo syndrome (MPS type III) is an autosomal recessive MPS with 4
recognized types (A-D). Each type is caused by a deficiency in 1 of 4 enzymes involved in the
degradation of heparan sulfate resulting in its lysosomal accumulation. Though biochemically different,
the clinical presentation of all types is indistinguishable. Sanfilippo syndrome is characterized by severe
central nervous system (CNS) degeneration, but other symptoms seen in MPS, such as coarse facial
features and skeletal involvement, tend to be milder. Onset of clinical features usually occurs between 2
and 6 years in a child who previously appeared normal. The presenting symptoms are most commonly
developmental delay and severe behavioral problems. Severe neurologic degeneration occurs in most
patients by 6 to 10 years of age, accompanied by a rapid deterioration of social and adaptive skills. Death
generally occurs by age 20, although individuals with an attenuated phenotype may have a longer life
expectancy. Sanfilippo syndrome type B is due to the absence of the enzyme
N-acetyl-alpha-D-glucosaminidase (alpha-hexosaminidase), caused by mutations in the NAGLU gene.
Diagnostic sequencing of the NAGLU gene (MP3BZ / Mucopolysaccharidosis IIIB, Full Gene Analysis)
and deletion/duplication studies are available for patients with an enzyme deficiency.
Useful For: Preferred assay for diagnosis of Sanfilippo syndrome type B (mucopolysaccharidoses
type IIIB)
Reference Values:
0.09-0.58 U/L
Clinical References: 1. Heron B, Mikaeloff Y, Froissart R, et al: Incidence and natural history of
mucopolysaccharidosis type III in France and comparison with United Kingdom and Greece. Am J Med
Genet A 2011;155A(1):58-68 2. Neufeld EF, Muenzer J: Chapter 136: The Mucopolysaccharidoses. In
The Metabolic and Molecular Bases of Inherited Disease. Eighth edition. Edited by D Valle, AL
Beaudet, B Vogelstein, et al. New York, McGraw-Hill Book Company. Available at
www.ommbid.com. Accessed 01/13/2015 3. Valstar MJ, Bruggenwirth HT, Olmer R, et al:
Mucopolysaccharidosis type IIIB may predominantly present with an attenuated clinical phenotype. J
Inherit Metab Dis 2010;33:759-767
Order MPCT / Muscle Pathology Consultation or MBCT / Muscle Biopsy Consultation, Outside
Slides and/or Paraffin Blocks. The consultant will determine the need for special stains.
Useful For: Adjunct in the diagnosis of pituitary tumors As part of the follow-up of treated pituitary
tumor patients Differential diagnosis of thyrotropin-secreting pituitary tumor versus thyroid hormone
resistance Differential diagnosis of constitutional delay of puberty versus hypogonadotrophic
hypogonadism
Interpretation: In the case of pituitary adenomas that do not produce significant amounts of intact
tropic hormones, diagnostic differentiation between sellar- and tumors of nonpituitary origin (eg,
meningiomas or craniopharyngiomas) can be difficult. In addition, if such nonsecreting adenomas are
very small, then they can be difficult to distinguish from physiological pituitary enlargements. In a
proportion of these cases, free alpha-subunit may be elevated, aiding in diagnosis. Overall, 5% to 30% of
pituitary adenomas produce measurable elevation in serum free alpha-subunit concentrations. There is
also evidence that an exuberant free alpha-subunit response to thyrotropin-releasing hormone (TRH)
administration may occur in some pituitary adenoma patients that do not have elevated baseline free
alpha-subunit levels. A more than 2-fold increase in free alpha-subunit serum concentrations at 30 to 60
minutes following intravenous administration of 500 mcg of TRH is generally considered abnormal, but
some investigators consider any increase of serum free alpha-subunit that exceeds the reference range as
abnormal. TRH testing is not performed in the laboratory, but in specialized clinical testing units under
the supervision of a physician. In pituitary tumors patients with pre-treatment elevations of serum free
alpha-subunit, successful treatment is associated with a reduction of serum free alpha-subunit levels.
Failure to lower levels into the normal reference range may indicate incomplete cure, and secondary rises
in serum free alpha-subunit levels can indicate tumor recurrence. Small thyrotropin (TSH)-secreting
pituitary tumors are difficult to distinguish from thyroid hormone resistance. Both types of patients may
appear clinically euthyroid or mildly hyperthyroid and may have mild-to-modest elevations in peripheral
thyroid hormone levels along with inappropriately (for the thyroid hormone level) detectable TSH, or
mildly-to-modestly elevated TSH. Elevated serum free alpha-subunit levels in such patients suggest a
TSH secreting tumor, but mutation screening of the thyroid hormone receptor gene may be necessary for a
definitive diagnosis. Constitutional delay of puberty (CDP), is a benign, often familial condition, in which
puberty onset is significantly delayed, but eventually occurs and then proceeds normally. By contrast,
hypogonadotrophic hypogonadism (HH) represents a disease state characterized by lack of gonadotropin
production. Its causes are varied, ranging from idiopathic over specific genetic abnormalities to
hypothalamic and pituitary inflammatory or neoplastic disorders. In children, it results in complete failure
to enter puberty without medical intervention. CDP and HH can be extremely difficult to distinguish from
each other. Intravenous administration of 100 mcg gonadotropin releasing hormone (GnRH) results in
much more substantial rise in free alpha-subunit levels in CDP patients, compared with HH patients. A
>6-fold rise at 30 or 60 minutes post-injection is seen in >75% of CDP patients, while a <2-fold rise
appears diagnostic of HH. Increments between 2-fold and 6-fold are nondiagnostic. GnRH testing is not
performed in the laboratory, but in specialized clinical testing units under the supervision of a physician.
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Reference Values:
PEDIATRIC
< or =5 days: < or =50 ng/mL
6 days-12 weeks: < or =10 ng/mL
3 months-17 years: < or =1.2 ng/mL
Tanner II-IV*: < or =1.2 ng/mL
ADULTS
Males: < or =0.5 ng/mL
Premenopausal females: < or =1.2 ng/mL
Postmenopausal females: < or =1.8 ng/mL
*Puberty onset (transition from Tanner stage I to Tanner stage II) occurs for boys at a median age of
11.5 (+/-2) years and for girls at a median age of 10.5 (+/-2) years. There is evidence that it may occur
up to 1 year earlier in obese girls and in African American girls. For boys, there is no proven
relationship between puberty onset and body weight or ethnic origin. Progression through Tanner stages
is variable. Tanner stage V (adult) should be reached by age 18.
Clinical References: 1. Preissner CM, Klee GG, Scheithauer BW, Abboud CF: Free alpha subunit
of the pituitary glycoprotein hormones. Am J Clin Pathol 1990;94:417-421 2. Mainieri AS, Viera JGH,
Elnecave RH: Response of the free alpha-subunit to GnRH distinguishes individuals with "functional"
from those with permanent hypogonadotropic hypogonadism. Horm Res 1998;50:212-216 3. Samejima
N, Yamada S, Takada K, et al: Serum alpha-subunit levels in patients with pituitary adenomas. Clin
Endocrinol 2001:54:479-484 4. Mainieri AS, Elnecave RH: Usefulness of the free alpha-subunit to
diagnose hypogonadotropic hypogonadism. Clin Endocrionol 2003;59:307-313 5. Socin HV, Chanson
P, Delemer B, et al: The changing spectrum of TSH-secreting pituitary adenomas: diagnosis and
management in 43 patients. Eur J Endocrinol 2003;148:433-442
Reference Values:
Reporting of immunofluorescent (IF) double staining for alpha 2 and alpha 5 chains of type IV collagen
on kidney biopsies:
1) Normal pattern of staining (ie, preserved linear alpha 5 staining of glomerular basement
membranes, Bowman capsule, and distal tubular basement membranes). This pattern of staining is seen
in normal individuals and patients with thin glomerular basement membrane disease but does not
exclude the diagnosis of hereditary nephritis/Alport syndrome.
2) Consistent with X-linked hereditary nephritis (Alport syndrome). There is global or segmental loss
of alpha 5 staining of glomerular basement membranes, Bowman capsule, and distal tubular basement
membranes. This pattern of loss of staining is usually due to mutations in the COL4A5 gene on the X
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chromosome.
3) Consistent with autosomal hereditary nephritis (Alport syndrome). There is global or segmental loss
of alpha 5 staining of glomerular basement membranes but preserved alpha 5 staining of Bowman
capsule and distal tubular basement membranes. This pattern of loss of staining is usually due to
mutations in the COL4A3 or COL4A4 genes on chromosome 2.
4) No interpretation can be reported if the specimen contains no intact glomeruli.
Reporting of IF double staining for alpha 2 and alpha 5 chains of type IV collagen on skin biopsies:
1) Normal pattern of staining (ie, preserved linear alpha 5 staining of epidermal basement
membranes). This pattern of staining is seen in normal individuals and patients with thin glomerular
basement membrane disease but does not exclude the diagnosis of hereditary nephritis/Alport
syndrome.
2) Consistent with X-linked hereditary nephritis (Alport syndrome): There is global or segmental loss
of alpha 5 staining of epidermal basement membranes. This pattern of loss of staining is usually due to
mutations in the COL4A5 gene on the X chromosome.
3) No interpretation can be reported if the biopsy contains no epidermis.
Notes:
1) Approximately one-third of patients with established hereditary nephritis based on typical
ultrastructural findings and family history show loss of glomerular basement membrane or epidermal
basement membrane staining for the alpha 5 chain of type IV collagen. Therefore, a normal staining
pattern does not exclude the diagnosis of hereditary nephritis.
2) In patients with hereditary nephritis, preserved alpha 5 staining indicates small mutations (eg,
missense, splice site) and is generally associated with a better renal outcome, while loss of alpha 5
staining indicates larger mutations (eg, deletion, nonsense, frame-shift) and a worse renal outcome.
3) Because alpha 3 and alpha 4 chains of type IV collagen are not expressed in the epidermal basement
membranes, patients with autosomal hereditary nephritis have preserved staining for alpha 5 on
epidermal basement membranes and, therefore, skin biopsy cannot exclude autosomal hereditary
nephritis.
4) Kagawa M, et al. Epitope-defined monoclonal antibodies against type-IV collagen for diagnosis of
Alport's syndrome. Nephrol Dial Transplant. 1997 Jun;12(6):1238-41.
Clinical References: 1. Markowitz GS, Gelber C, DAgati VD: An 18-year-old male with
hematuria, renal insufficiency, and defective synthesis of type IV collagen. Kidney Int
2006;69(12):2278-2282 2. Van Der Loop FTL, Monnens LAH, Schroder CH, et al: Identification of
COL4A5 defects in Alports syndrome by immunohistochemistry of skin. Kidney Int
1999;55(4):1217-1224 3. Gubler MC, Knebelmann B, Beziau A, et al: Autosomal recessive Alport
syndrome: immunohistochemical study of type IV collagen chain distribution. Kidney Int
1995;47(4):1142-1147
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Monitoring aluminum exposure Monitoring metallic prosthetic implant wear
Interpretation: Daily excretion less than 10 mcg/24 hours indicates exposure to excessive amounts
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of aluminum. In renal failure, the ability of the kidney to excrete aluminum decreases, while the
exposure to aluminum increases (aluminum-laden dialysis water, aluminum-laden albumin, and
aluminum-laden phosphate binders). Patients receiving chelation therapy with desferrioxamine (for
iron- or aluminum-overload states) also excrete considerably more aluminum in their urine than normal.
Prosthesis wear is known to result in increased circulating concentration of metal ions.(1,2) Modest
increase (10-20 mcg/24 hours) in urine aluminum concentration is likely to be associated with a
prosthetic device in good condition. Urine concentrations above 50 mcg/ 24 hours in a patient with an
aluminum-based implant, not undergoing dialysis, suggests significant prosthesis wear. Increased urine
trace element concentrations in the absence of corroborating clinical information do not independently
predict prosthesis wear or failure.
Reference Values:
0-17 years: not established
> or = 18 years: <10 mcg/24h
Clinical References: 1. O'Shea S, Johnson DW: Review article: addressing risk factors in chronic
kidney disease mineral and bone disorder: can we influence patient-level outcomes? Nephrology
2009;14:416-427 2. Meyer-Baron M, Schuper M, Knapp G, van Thriel C: Occupational aluminum
exposure: evidence in support of its neurobehavioral impact. Neurotoxicology 2007;28:1068-1078
AL Aluminum, Serum
8373 Clinical Information: Under normal physiologic conditions, the usual daily dietary intake of
aluminum (5-10 mg) is completely eliminated. Excretion is accomplished by avid filtration of aluminum
from the blood by the glomeruli of the kidney. Patients in renal failure (RF) lose the ability to clear
aluminum and are candidates for aluminum toxicity. Many factors increase the incidence of aluminum
toxicity in RF patients: -Aluminum-laden dialysis water can expose dialysis patients to aluminum.
-Aluminum-laden albumin can expose patients to an aluminum burden they cannot eliminate. -The
dialysis process is not highly effective at eliminating aluminum. -Aluminum-based phosphate binder gels
are administered orally to minimize phosphate accumulation; a small fraction of this aluminum may be
absorbed and accumulated. If it is not removed by renal filtration, aluminum accumulates in the blood,
where it binds to proteins such as albumin and is rapidly distributed through the body. Aluminum
overload leads to accumulation of aluminum at 2 sites: brain and bone. Brain deposition has been
implicated as a cause of dialysis dementia. In bone, aluminum replaces calcium at the mineralization
front, disrupting normal osteoid formation. Deposition of aluminum in bone also interrupts normal
calcium exchange. The calcium in bone becomes unavailable for resorption back into blood under the
physiologic control of parathyroid hormone (PTH) and results in secondary hyperparathyroidism. While
PTH is typically quite elevated in RF, 2 different processes may occur: 1) High-turnover bone disease
associated with high PTH (>150 pg/mL) and relatively low aluminum (<20 ng/mL), or 2) low-turnover
bone disease with lower PTH (<50 pg/mL) and high aluminum (>60 ng/mL). Low-turnover bone disease
indicates aluminum intoxication. Serum aluminum concentrations are likely to be increased above the
reference range in patients with metallic joint prosthesis. Prosthetic devices produced by Zimmer
Company and Johnson and Johnson typically are made of aluminum, vanadium, and titanium. Prosthetic
devices produced by Depuy Company, Dow Corning, Howmedica, LCS, PCA, Osteonics, Richards
Company, Tricon, and Whiteside, typically are made of chromium, cobalt, and molybdenum. This list of
products is incomplete, and these products change occasionally; see prosthesis product information for
each device for composition details.
Useful For: Preferred monitoring for aluminum toxicity in patients undergoing dialysis Preferred test
for routine aluminum screening Monitoring metallic prosthetic implant wear
Interpretation: Patients in renal failure not receiving dialysis therapy invariably have serum aluminum
levels above the 60 ng/mL range. McCarthy(1) and Hernandez(2) describe a biochemical profile that is
characteristic of aluminum overload disease in dialysis patients: -Patients in renal failure with no signs or
symptoms of osteomalacia or encephalopathy usually had serum aluminum below 20 ng/mL and
parathyroid hormone (PTH) concentrations above 150 pg/mL, which is typical of secondary
hyperparathyroidism. -Patients with signs and symptoms of osteomalacia or encephalopathy had serum
aluminum above 60 ng/mL and PTH concentrations below 50 pg/mL (PTH above the reference range, but
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low for secondary hyperparathyroidism). -Patients who had serum aluminum above 60 ng/mL and below
100 ng/mL were identified as candidates for later onset of aluminum overload disease that required
aggressive efforts to reduce their daily aluminum exposure. This was done by switching them from
aluminum-containing phosphate binders to calcium-containing phosphate binders, by ensuring that their
dialysis water had less than 10 ng/mL of aluminum, and ensuring the albumin used during postdialysis
therapy was aluminum-free. Prosthesis wear is known to result in increased circulating concentration of
metal ions.(3) Modest increase (6-10 ng/mL) in serum aluminum concentration is likely to be associated
with a prosthetic device in good condition. Serum concentrations above 10 ng/mL in a patient with an
aluminum-based implant not undergoing dialysis suggest significant prosthesis wear. Increased serum
trace element concentrations in the absence of corroborating clinical information do not independently
predict prosthesis wear or failure.
Reference Values:
0-6 ng/mL (all ages)
<60 ng/mL (dialysis patients-all ages)
Clinical References: 1. McCarthy JT, Milliner DS, Kurtz SB, et al: Interpretation of serum
aluminum values in dialysis patients. Am J Clin Pathol 1986;86:629-636 2. Hernandez JD, Wesseling
K, Salusky IB: Role of parathyroid hormone and therapy with active vitamin D sterols in renal
osteodystrophy. Sem Dialysis 2005;18:290-295 3. Liu TK, Liu SH, Chang CH, Yang RS: Concentration
of metal elements in the blood and urine in the patients with cementless total knee arthroplasty. Tohoku
J Exp Med 1998;185:253-262 4. Schwarz C, Sulzbacher R, Oberbauer R: Diagnosis of renal
osteodystrophy. Eur J Clin Invest 2006;36:13-22
Useful For: Monitoring aluminum exposure when a 24-hour urine cannot be collected Monitoring
metallic prosthetic implant wear when a 24-hour urine cannot be collected
Interpretation: Daily excretion more than 10 mcg/24 hours indicates exposure to aluminum.
Prosthesis wear is known to result in increased circulating concentration of metal ions.(1) Modest
increase (10-20 mcg/24 hours) in urine aluminum concentration is likely to be associated with a
prosthetic device in good condition. Urine concentrations more than 50 mcg/24 hours in a patient with
an aluminum-based implant, not undergoing dialysis, suggest significant prosthesis wear. Increased
urine trace element concentrations in the absence of corroborating clinical information do not
independently predict prosthesis wear or failure. In renal failure, the ability of the kidney to excrete
aluminum decreases, while the exposure to aluminum increases (aluminum-laden dialysis water,
aluminum-laden albumin, and aluminum-laden phosphate binders). Patients receiving chelation therapy
with desferrioxamine (for iron- or aluminum-overload states) also excrete considerably more aluminum
in their urine than normal.
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Reference Values:
0-17 years: not established
> or =18 years: <14 mcg/g Creatinine
Clinical References: 1. Liu TK, Liu SH, Chang CH, Yang RS: Concentration of metal elements in
the blood and urine in the patients with cementless total knee arthroplasty. Tohoku J Exp Med
1998;185:253-262 2. O'Shea S, Johnson DW: Review article: Addressing risk factors in chronic kidney
disease mineral and bone disorder: Can we influence patient-level outcomes? Nephrology
2009;14:416-427 3. Meyer-Baron M, Schuper M, Knapp G, van Thriel C: Occupational aluminum
exposure: Evidence in support of its neurobehavioral impact. NeuroToxicology 2007;28:1068-1078
Useful For: Supporting the diagnosis of alveolar rhabdomyosarcomas (ARMS) when used in
conjunction with an anatomic pathology consultation Aids in the diagnosis of ARMS when reverse
transcriptase-PCR results are equivocal or do not support the clinical picture
Interpretation: A neoplastic clone is detected when the percent of cells with an abnormality exceeds
the normal cutoff for the FOXO1 FISH probe. A positive result suggests rearrangement of the FOXO1
gene region at 13q14 and is consistent with a subset of alveolar rhabdomyosarcomas (ARMS). A negative
result suggests FOXO1 gene rearrangement is not present, but does not exclude the diagnosis of alveolar
rhabdomyosarcomas (ARMS).
Reference Values:
An interpretive report will be provided.
Reference Values:
An interpretative report will be provided.
Clinical References: 1. Edwards RH, Chatten J, Xiong QB, Barr FG: Detection of gene fusions in
rhabdomyosarcoma by reverse transcriptase polymerase chain reaction assay of archival samples. Diagn
Mol Pathol 1997;6:91-97 2. Ladanyi M, Bridge JA: Contribution of molecular genetic data to the
classification of sarcomas. Hum Pathol 2000;31:532-538 3. Galili N, Davis RJ, Fredricks WJ, et al:
Fusion of a fork head domain gene to PAX3 in the solid tumor alveolar rhabdomyosarcoma. Nat Genet
1993;5:230-235 4. Jin L, Majerus J, Oliveira A, et al: Detection of fusion gene transcripts in
fresh-frozen and formalin-fixed paraffin-embedded tissue sections of soft tissue sarcomas after laser
capture microdissection and RT-PCR. Diagn Mol Pathol 2003;12:224-230
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slow growing and refractory to chemotherapy with a propensity to metastasize. Prolonged survival is
possible even with metastasis, although the long-term disease-related mortality rate is high. ASPS is
characterized by a translocation that results in fusion of TFE3 on chromosome Xp11.2 with ASPSCR1
(also called ASPL or RCC17) on chromosome 17q25.3. Both balanced and unbalanced forms (loss of
the derivative X chromosome) of the translocation have been observed. Another tumor, a rare subset of
papillary renal cell carcinoma (RCC) with a distinctive pathologic morphology, has rearrangements of
TFE3 with ASPSCR1 or other fusion partner genes. This tumor predominantly affects children and
young adults, presents at an advanced stage but with an indolent clinical course, and is a distinct entity
in the World Health Organization classification. Typically a balanced form of the translocation is
present in the RCC variant. An assay to detect rearrangement of TFE3 is useful to resolve diagnostic
uncertainty in these tumor types, as immunohistochemistry for TFE3 is not reliable.
Useful For: An aid in the diagnosis of alveolar soft-part sarcoma or renal cell carcinoma variant when
used in conjunction with an anatomic pathology consultation
Interpretation: A neoplastic clone is detected when the percent of nuclei with the abnormality exceeds
the established normal cutoff for the TFE3 probe set. A positive result of TFE3 rearrangement is
consistent with a diagnosis of alveolar soft-part sarcoma (ASPS) or renal cell carcinoma (RCC) variant. A
negative result suggests that TFE3 is not rearranged, but does not exclude the diagnosis of ASPS or RCC
variant.
Reference Values:
An interpretive report will be provided.
Expected steady state amantadine concentrations in patients receiving recommended daily dosages:
200-1000 ng/mL
Toxicity reported at greater than 2000 ng/mL
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Useful For: Monitoring adequacy of serum concentration during amikacin therapy
Interpretation: For conventional (nonpulse) dosing protocols, clinical effects may not be achieved if
the peak serum concentration is <20.0 mcg/mL. Toxicity may occur if the peak serum concentration is
maintained >35.0 mcg/mL for a prolonged period of time.
Reference Values:
Peak: 20.0-35.0 mcg/mL Toxic peak: >40.0 mcg/mL
Clinical References: 1. Wilson JW, Estes LL: Mayo Clinic Antimicrobial Therapy Quick Guide,
2008 2. Hammett-Stabler CA, Johns T: Laboratory guidelines for monitoring of antimicrobial drugs.
national academy of clinical biochemistry. Clin Chem 1998 May;44(5):1129-1140 3. Gonzalez LS III,
Spencer JP: Aminoglcosides: a practical review. Am Fam Physician 1998 Nov 15;58(8):1811-1820
Reference Values:
Peak: 20.0-35.0 mcg/mL
Toxic peak: >40.0 mcg/mL
Trough: <8.0 mcg/mL
Toxic trough:>10.0 mcg/mL
Clinical References: 1. Wilson JW, Estes LL: Mayo Clinic Antimicrobial Therapy Quick Guide,
2008 2. Hammett-Stabler CA, Johns T: Laboratory Guidelines for Monitoring of Antimicrobial Drugs.
National Academy of Clinical Biochemistry. Clin Chem. 1998 May;44(5):1129-1140 3. Gonzalez LS
III, Spencer JP: Aminoglcosides: a practical review. Am Fam Physician 1998 Nov 15;58(8):1811-1820
Useful For: Monitoring adequate clearance of amikacin near the end of a dosing cycle
Interpretation: For conventional (nonpulse) dosing protocols, trough concentrations should fall to
<8.0 mcg/mL. Toxicity may occur if the trough serum concentration is maintained >10.0 mcg/mL for
prolonged periods of time.
Reference Values:
Trough: <8.0 mcg/mL Toxic trough: >10.0 mcg/mL
Clinical References: 1. Wilson JW, Estes LL: Mayo Clinic Antimicrobial Therapy Quick Guide,
2008 2. Hammett-Stabler CA, Johns T: Laboratory guidelines for monitoring of antimicrobial drugs.
National Academy of Clinical Biochemistry.. Clin Chem 1998 May;44(5):1129-1140 3. Gonzalez LS III,
Spencer JP: Aminoglcosides: a practical review. Am Fam Physician 1998 Nov 15;58(8):1811-1820
Useful For: Follow-up of patients with maple syrup urine disease Monitoring of dietary compliance for
patients with maple syrup urine disease
Interpretation: The quantitative results of isoleucine, leucine, valine, and allo-isoleucine with
age-dependent reference values are reported without added interpretation. When applicable, reports of
abnormal results may contain an interpretation based on available clinical interpretation.
Reference Values:
ISOLEUCINE
< or =23 months: 31-105 nmol/mL
2-17 years: 30-111 nmol/mL
> or =18 years: 36-107 nmol/mL
LEUCINE
< or =23 months: 48-175 nmol/mL
2-17 years: 51-196 nmol/mL
> or =18 years: 68-183 nmol/mL
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VALINE
< or =23 months: 83-300 nmol/mL
2-17 years: 106-320 nmol/mL
> or =18 years: 136-309 nmol/mL
ALLO-ISOLEUCINE
< or =23 months: <2 nmol/mL
2-17 years: <3 nmol/mL
> or =18 years: <5 nmol/mL
Clinical References: 1. Scriver's The Online Metabolic and Molecular Bases of Inherited Disease
(OMMBID). Part 8 Amino Acids. Accessed July 6, 2016. Available at:
http://ommbid.mhmedical.com/book.aspx?bookid=971 2. Chuang DT, Shih VE, Max Wynn RR: In
Maple Syrup Urine Disease (Branched-Chain Ketoaciduria). Edited by D Valle, AL Beaudet, B
Vogelstein, et al. New York, NY, McGraw-Hill, 2014. Accessed July 6, 2016. Available at
http://ommbid.mhmedical.com/content.aspx?bookid=971&Sectionid=62675436. 3. Strauss KA,
Puffenberger EG, Morton DH:.In Maple Syrup Urine Disease. 1993-2016. Edited by RA Pagon, MP
Adam, HH Ardinger. GeneReviews. University of Washington, Seattle, WA. Updated 2013 May 9.
Available at: http://www.ncbi.nlm.nih.gov/books/NBK1319
Useful For: Evaluating patients with possible inborn errors of metabolism May aid in evaluation of
endocrine disorders, liver diseases, muscle diseases, neoplastic diseases, neurological disorders,
nutritional disturbances, renal failure, and burns
Reference Values:
Plasma Amino Acid Reference Values (nmol/mL) Age Groups
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Phosphoserine (PSer)
Phosphoethanolamine (PEtN)
Ethanolamine (EtN)
b-Alanine (bAla)
1-Methylhistidine (1MHis)
Carnosine (Car)
Anserine (Ans)
Homocitruline (Hcit)
Hydroxylysine (Hyl)
Cystathionine (Cth)
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Leucine (Leu) 48-175 51-196 68-183
Alloisoleucine (Allolle)
Clinical References: Scriver's The Online Metabolic and Molecular Bases of Inherited Disease
(OMMBID). Part 8 Amino Acids. Accessed July 6, 2016. Available at
http://ommbid.mhmedical.com/book.aspx?bookid=971
Useful For: Evaluating patients with possible inborn errors of metabolism May aid in evaluation of
endocrine disorders, liver diseases, muscle diseases, neoplastic diseases, neurological disorders,
nutritional disturbances, renal failure, and burns
Reference Values:
Urine Amino Acid Reference Values Age Groups
(nmol/mg creatinine)
< or =12 13-35 3-6 Years 7-8 Years 9-17 Years > or =18
Months Months Years
Phosphoserine PSer
Hydroxyproline Hyp
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Glycine Gly 362-18614 627-6914 412-5705 449-4492 316-4249 229-2989
Citrulline Cit
Sarcosine Sar
Beta-Alanine bAla
Anserine Ans
Alpha-amino-n-butyric Abu
Acid
Hydroxylysine Hyl
Ornithine Orn
Cystathionine Cth
Methionine Met
Isoleucine Ile
Allo-isoleucine AlloIle
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Clinical References: 1. Scriver's The Online Metabolic and Molecular Bases of Inherited Disease
(OMMBID). Part 8 Amino Acids. Accessed July 6, 2016. Available at:
http://ommbid.mhmedical.com/book.aspx?bookid=971 2. Camargo SMR, Bockenhauer D, Kleta R:
Aminoacidurias: Clinical and molecular aspects. Kidney Int 2008;73:918-925
Useful For: Evaluating patients with possible inborn errors of amino acid metabolism, in particular
nonketotic hyperglycinemia and serine biosynthesis defects, especially when used in conjunction with
concomitantly drawn plasma specimens.
Reference Values:
CSF Amino Acid Reference ValuesAge Groups
(nmol/mL)
< or =31 Days 32 Days-23 Months 2-18 Years (n=189) > or =19 Years
(n=73) (n=88) (n=32)
Phosphoserine (PSer)
Phosphoethanolamine (PEtN)
Taurine (Tau) 8-48
Hydroxyproline (Hyp)
Citrulline (Cit)
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Sarcosine (Sar)
Beta-alanine (bAla)
1-Methylhistidine (1MHis)
3-Methylhistidine (3MHis)
Carnosine (Car)
Anserine (Ans)
Homocitrulline (Hcit)
Gamma-amino-n-butyric Acid
(GABA)
Hydroxylysine (Hyl)
Proline (Pro)
Ornithine (Orn)
Cystathionine (Cth)
Cystine (Cys)
Methionine (Met)
Homocystine (Hcy)
Isoleucine (Ile)
Leucine (Leu) 12-41 6-21 7-16 7-29
Tryptophan (Trp)
Allo-isoleucine (AlloIle)
Clinical References: Rinaldo P, Hahn S, Matern D: Inborn errors of amino acid, organic acid, and
fatty acid metabolism. In Tietz Textbook of Clinical Chemistry and Molecular Diagnosis. Fourth
edition. Edited by CA Burtis, ER Ashwood, DE Bruns. St. Louis, WB Saunders Company, 2005, pp
2207-2247
Useful For: Differential diagnosis and follow-up of patients with urea cycle disorders
Interpretation: The quantitative results of glutamine, ornithine, citrulline, arginine, and
argininosuccinic acid with age-dependent reference values are reported without added interpretation.
When applicable, reports of abnormal results may contain an interpretation based on available clinical
interpretation.
Reference Values:
GLUTAMINE
< or =23 months: 316-1020 nmol/mL
2-17 years: 329-976 nmol/mL
> or =18 years: 371-957 nmol/mL
ORNITHINE
< or =23 months: 20-130 nmol/mL
2-17 years: 22-97 nmol/mL
> or =18 years: 38-130 nmol/mL
CITRULLINE
< or =23 months: 9-38 nmol/mL
2-17 years: 11-45 nmol/mL
> or =18 years: 17-46 nmol/mL
ARGININE
< or =23 months: 29-134 nmol/mL
2-17 years: 31-132 nmol/mL
> or =18 years: 32-120 nmol/mL
ARGININOSUCCINIC ACID
<2 nmol/mL
Reference value applies to all ages.
Clinical References: 1. Scriver's The Online Metabolic and Molecular Bases of Inherited Disease
(OMMBID). Part 8 Amino Acids. Accessed July 6, 2016. Available at:
http://ommbid.mhmedical.com/book.aspx?bookid=971 2. Haberle J, Boddaert N, Burlina A, Chakrapani
A, et al: Suggested guidelines for diagnosis and management of urea cycle disorders. Orphanet J Rare
Dis 2012;7:32 3. Singh RH: Nutritional management of patients with urea cycle disorders. J Inher
Metab Dis 2007;30(6):880-887 4. Foshci FG, Morelli MC, Savini S, et al: Urea cycle disorders: A case
report of a successful liver transplant and a literature review. World J Gastroenterol 2015 Apr
7;21(13):4063-4068
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ALAUR Aminolevulinic Acid (ALA), Urine
61547 Clinical Information: The porphyrias are a group of inherited disorders resulting from enzyme
defects in the heme biosynthetic pathway. Depending on the specific enzyme involved, various porphyrins
and their precursors accumulate in different specimen types. The patterns of porphyrin accumulation in
erythrocytes and plasma and excretion of the heme precursors in urine and feces allow for the detection
and differentiation of the porphyrias. The porphyrias are typically classified as erythropoietic or hepatic
based upon the primary site of the enzyme defect. In addition, hepatic porphyrias can be further classified
as chronic or acute, based on their clinical presentation. The primary acute hepatic porphyrias:
aminolevulinic acid dehydratase deficiency porphyria (ADP), acute intermittent porphyria (AIP),
hereditary coproporphyria (HCP), and variegate porphyria (VP), are associated with neurovisceral
symptoms that typically onset during puberty or later. Common symptoms include severe abdominal pain,
peripheral neuropathy, and psychiatric symptoms. A broad range of medications (including barbiturates
and sulfa drugs), alcohol, infection, starvation, heavy metals, and hormonal changes may precipitate
crises. Photosensitivity is not associated with AIP, but may be present in HCP and VP. The excretion of
aminolevulinic acid (ALA) can be increased due to one of the inherited acute porphyrias or due to
secondary inhibition of ALA dehydratase. Among the secondary causes, acute lead intoxication results in
the highest degree of aminolevulinic aciduria. Less significant elevations are seen in chronic lead
intoxication, tyrosinemia type I, alcoholism, and pregnancy. The workup of patients with a suspected
porphyria is most effective when following a stepwise approach. See Porphyria (Acute) Testing
Algorithm and Porphyria (Cutaneous) Testing Algorithm in Special Instructions or contact Mayo Medical
Laboratories to discuss testing strategies.
Useful For: Assistance in the differential diagnosis of the various acute hepatic porphyrias
Interpretation: Abnormal results are reported with a detailed interpretation that may include an
overview of the results and their significance, a correlation to available clinical information provided with
the specimen, differential diagnosis, recommendations for additional testing when indicated and available,
and a phone number to reach one of the laboratory directors in case the referring physician has additional
questions.
Reference Values:
<1 year: < or =10 nmol/mL
1-17 years: < or =20 nmol/mL
> or =18 years: < or =15 nmol/mL
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9-12 years 300-1300 300-1300
Interpretation: Abnormal results are reported with a detailed interpretation including an overview of
the results and their significance, a correlation to available clinical information provided with the
specimen, differential diagnosis, and recommendations for additional testing when indicated and
available, and a phone number to reach a laboratory director in case the referring physician has
additional questions.
Reference Values:
Reference ranges have not been established for patients who are <16 years of age.
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ALAD Aminolevulinic Acid Dehydratase (ALAD), Whole Blood
88924 Clinical Information: Porphyrias are a group of inherited disorders resulting from enzyme defects in
the heme biosynthetic pathway. A defect in the second enzyme of this pathway causes 5-aminolevulinic
acid (ALA) dehydratase (ALAD) deficiency porphyria (ADP). A marked deficiency of ALAD causes the
accumulation and subsequent urinary excretion of large amounts of ALA. Urinary porphobilinogen (PBG)
remains essentially normal, which rules out other forms of acute porphyria. ADP is an autosomal
recessive acute hepatic porphyria that produces neurologic symptoms similar to those seen in acute
intermittent porphyria. Symptoms include acute abdominal pain, peripheral neuropathy, nausea, vomiting,
constipation, and diarrhea. Respiratory impairment, seizures, and psychosis are possible during an acute
period. ADP is extremely rare with only 7 cases described in the literature since 1979. The workup of
patients with a suspected porphyria is most effective when following a stepwise approach. See Porphyria
(Acute) Testing Algorithm in Special Instructions or contact Mayo Medical Laboratories to discuss
testing strategies.
Useful For: This test is the preferred test for the confirmation of a diagnosis of aminolevulinic acid
dehydratase deficiency porphyria This test will not detect lead intoxication.
Interpretation: Abnormal results are reported with a detailed interpretation including an overview of
the results and their significance, a correlation to available clinical information provided with the
specimen, differential diagnosis, and recommendations for additional testing when indicated and
available, and a phone number to reach a laboratory director in case the referring physician has additional
questions.
Reference Values:
Reference ranges have not been established for patients who are <16 years of age.
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thyroid hormones. Neurological and gastrointestinal toxicities are concentration-dependent, whereas
thyroid dysfunction, pulmonary fibrosis, and hepatotoxicity are more loosely linked to drug concentration.
There is significant potential for drug interactions involving amiodarone, including several other
cardioactive drugs (eg, digoxin, verapamil, class I antiarrhythmics [sodium channel blockers]), warfarin,
statins, and CYP3A4 substrates.
Useful For: Monitoring amiodarone therapy, especially when amiodarone is coadministered with
other drugs that may interact Evaluation of possible amiodarone toxicity Assessment of patient
compliance
Interpretation: Clinical effects generally require serum concentrations >0.5 mcg/mL. Increased risk
of toxicity is associated with amiodarone concentrations >2.5 mcg/mL. Although therapeutic and toxic
ranges are based only on the parent drug, the active metabolite N-desethylamiodarone should be present
in similar concentrations to amiodarone.
Reference Values:
AMIODARONE
Therapeutic concentration: 0.5-2.0 mcg/mL
Toxic concentration: >2.5 mcg/mL
DESETHYLAMIODARONE
No therapeutic range established; activity and serum concentration are similar to parent drug.
Clinical References: 1. Goldschlager N, Epstein AE, Naccarelli GV, et al: A practical guide for
clinicians who treat patients with amiodarone. Heart Rhythm 2007;4:1250-1259 2. Klotz U:
Antiarrhythmics: elimination and dosage considerations in hepatic impairment. Clin
Pharmacokinet.2007;46(12):985-996 3. Campbell TJ, Williams KM: Therapeutic drug monitoring:
antiarrhythmic drugs. Br J Clin Pharmacol.2001;52 Suppl1:21S-34S
Useful For: Monitoring serum concentration during therapy Evaluating potential toxicity The test
may also be useful to evaluate patient compliance
Interpretation: Most individuals display optimal response to amitriptyline when combined serum
levels of amitriptyline and nortriptyline are between 80 and 200 ng/mL. Risk of toxicity is increased
with combined levels are above 500 ng/mL. Most individuals display optimal response to nortriptyline
with serum levels between 70 and 170 ng/mL. Risk of toxicity is increased with nortriptyline levels
above 500 ng/mL. Some individuals may respond well outside of these ranges, or may display toxicity
within the therapeutic range, thus, interpretation should include clinical evaluation. Therapeutic ranges
are based on specimens drawn at trough (ie, immediately before the next dose).
Reference Values:
AMITRIPTYLINE AND NORTRIPTYLINE
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Total therapeutic concentration: 80-200 ng/mL
NORTRIPTYLINE ONLY
Therapeutic concentration: 70-170 ng/mL
Note: Therapeutic ranges are for specimens drawn at trough (ie, immediately before next scheduled
dose). Levels may be elevated in non-trough specimens.
Clinical References: 1. Wille SM, Cooreman SG, Neels HM, Lambert WE: Relevant issues in the
monitoring and the toxicology of antidepressants. Crit Rev Clin Lab Sci 2008;45(1):25-89 2. Thanacoody
HK, Thomas SH: Antidepressant poisoning. Clin Med 2003;3(2):114-118 3. Hiemke C, Baumann P,
Bergemann N, et al: AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Psychiatry: Update
2011. Pharmacopsychiatry 2011;44(6):195-235 4. Tietz Textbook of Clinical Chemistry and Molecular
Diagnostics. Edited by CA Burtis, ER Ashwood, DE Bruns. 2012. Fifth edition. Elsevier
Useful For: Assisting in the diagnosis of hepatic coma Investigating and monitoring treatment for
inborn errors of metabolism Evaluating patients with advanced liver disease
Interpretation: Plasma ammonia concentrations do not correlate well with the degree of hepatic
encephalopathy. Elevated ammonia concentration may also be found with increased dietary protein
intake.
Reference Values:
< or =30 mcmol/L
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acid load of that given patient.(4)
Useful For: Diagnosis of the cause of an acidosis Diagnosis and treatment of kidney stones
Interpretation: If a patient has an acidosis, and the amount of ammonium in the urine is low, this
suggests a renal tubular acidosis. If the amount of ammonium is high, this suggests that the kidneys are
working normally and that there are other losses of bicarbonate in the body. Typically this implies
gastrointestinal losses.
Reference Values:
15-56 mmol/24 hour
Reference values have not been established for patients <18 years and >77 years of age.
Reference values apply to 24 hour collections.
Clinical References: 1. Peonides A, Levin B, Young W: The renal excretion of hydrogen ions in
infants and children. Arch Dis Child 1965 February;40(209):33-39 2. Kamel, KS, Briceno LF, Sanchez
MI, et al: A new classification for renal defects in net acid excretion. Am J Kidney Dis 1997
Jan;29(1):136-146 3. Madison LL, Seldin DW: Ammonia excretion and renal enzymatic adaptation in
human subjects, as disclosed by administration of precursor amino acids. J Clin Invest 1958
November;37(11):1615-1627 4. Coe FL, Evan A, Worcester E: Pathophysiology-Based Treatment of
Idiopathic Calcium Kidney Stones. Clin J Am Soc Nephrol 2011 Aug;6(8):2083-2092
Useful For: Diagnosis of the cause of an acidosis Diagnosis and treatment of kidney stones
Interpretation: If a patient has an acidosis, and the amount of ammonium in the urine is low, this
suggests a renal tubular acidosis. If the amount of ammonium is high, this suggests that the kidneys are
working normally and that there are other losses of bicarbonate in the body. Typically this implies
gastrointestinal losses.
Reference Values:
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Random: 3-65 mmol/L
No reference values established for <18 years and >77 years of age.
Clinical References: 1. Peonides A, Levin B, Young W: The renal excretion of hydrogen ions in
infants and children. Arch Dis Child 1965 February;40(209):33-39 2. Kamel KS, Briceno LF, Sanchez
MI, et al: A new classification for renal defects in net acid excretion. Am J Kidney Dis 1997
Jan;29(1):136-146 3. Madison LL, Seldin DW: Ammonia excretion and renal enzymatic adaptation in
human subjects, as disclosed by administration of precursor amino acids. J Clin Invest 1958
November;37(11):1615-1627 4. Coe FL, Evan A, Worcester E: Pathophysiology-Based Treatment of
Idiopathic Calcium Kidney Stones. Clin J Am Soc Nephrol 2011 Aug;6(8):2083-2092
Useful For: Producing amniocyte cultures that can be used for genetic analysis Once confluent flasks
are established, the amniocyte cultures are sent to other laboratories, either within Mayo Clinic or to
external sites, based on the specific testing requested.
Reference Values:
Not applicable
Clinical References: Barch MJ, Knutsen T, Spurbeck JL: In The AGT Cytogenetics Laboratory
Manual. Third edition, 1997
Reference Values:
Therapeutic concentration: 1.0-5.0 mcg/mL
Toxic concentration: >10.0 mcg/mL
Concentration at which toxicity occurs varies and should be interpreted in light of clinical situation.
Clinical References: 1. Goodman and Gilman's: The Pharmacological Basis of Therapeutics. 10th
edition. New York, McGraw-Hill Book Company, 2001 2. Teitz Textbook of Clinical Chemistry and
Molecular Diagnostics. Fourth edition. St. Louis, MO, Elsevier Saunders, 2006, pp 1091 3. Disposition of
Toxic Drugs and Chemicals in Man. Seventh edition. Edited by RC Baselt. Foster City, CA, Biomedical
Publications, 2004, pp 1254
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8-Hydroxyamoxapine No reference range provided ng/mL
Combined Total 200 400 ng/mL
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Order MPCT / Muscle Pathology Consultation or MBCT / Muscle Biopsy Consultation, Outside
Slides and/or Paraffin Blocks. The consultant will determine the need for special stains.
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FAMP Amphetamine, Serum or Plasma
91171 Reference Values:
Reference Range: 10 100 ng/mL
Useful For: Detection of in utero drug exposure up to 5 months before birth Chain of custody is
required whenever the results of testing could be used in a court of law. Its purpose is to protect the rights
of the individual contributing the specimen by demonstrating that it was under the control of personnel
involved with testing the specimen at all times; this control implies that the opportunity for specimen
tampering would be limited. Since the evidence of illicit drug use during pregnancy can be cause for
separating the baby from the mother, a complete chain of custody ensures that the test results are
appropriate for legal proceedings.
Reference Values:
Negative
Positives are reported with a quantitative LC-MS/MS result.
Cutoff concentrations:
Amphetamine by LC-MS/MS: 50 ng/g
Methamphetamine by LC-MS/MS: 50 ng/g
3,4-Methylenedioxyamphetamine by LC-MS/MS: 50 ng/g
3,4-Methylenedioxyethylamphetamine by LC-MS/MS: 50 ng/g
3,4-Methylenedioxymethamphetamine by LC-MS/MS: 50 ng/g
Clinical References: 1. Disposition of Toxic Drugs and Chemical in Man. Edited by RC Baselt.
Foster City, CA, Biochemical Publications, 2008 pp 83-86; 947-952; 993-999 2. Ostrea EM Jr, Brady MJ,
Parks PM, et al: Drug screening of meconium in infants of drug-dependent mothers: an alternative to
urine testing. J Pediatr 1989;115:474-477 3. Ahanya SN, Lakshmanan J, Morgan BL, Ross MG:
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Meconium passage in utero: mechanisms, consequences, and management. Obstet Gynecol Surv
2005;60:45-56 4. Kwong TC, Ryan RM: Detection of intrauterine illicit drug exposure by newborn drug
testing. National Academy of Clinical Biochemistry. Clin Chem 1997;43:235-242 5. Dixon SD: Effects of
transplacental exposure to cocaine and methamphetamine on the neonate. West J Med 1989;150:436-442
Reference Values:
Negative
Positives are reported with a quantitative LC-MS/MS result.
Cutoff concentrations:
AMPHETAMINE BY LC-MS/MS
50 ng/g
METHAMPHETAMINE BY LC-MS/MS
50 ng/g
3,4-METHYLENEDIOXYAMPHETAMINE BY LC-MS/MS
50 ng/g
3,4-METHYLENEDIOXYMETHAMPHETAMINE BY LC-MS/MS
50 ng/g
3,4-METHYLENEDIOXYMETHAMPHETAMINE BY LC-MS/MS
50 ng/g
Clinical References: 1. Disposition of Toxic Drugs and Chemical in Man. Edited by RC Baselt.
Foster City, CA, Biochemical Publications, 2008 pp 83-86; 947-952; 993-999 2. Ostrea EM Jr, Brady
MJ, Parks PM, et al: Drug screening of meconium in infants of drug-dependent mothers: and alternative
to urine testing. J Pediatr 1989;115:474-477 3. Ahanya SN, Lakshmanan J, Morgan BL, Ross MG:
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 139
Meconium passage in utero: mechanisms, consequences, and management. Obstet Gynecol Surv
2005;60:45-56 4. Kwong TC, Ryan RM: Detection of intrauterine illicit drug exposure by newborn drug
testing. National Academy of Clinical Biochemistry. Clin Chem 1997;43:235-242 5. Dixon SD: Effects
of transplacental exposure to cocaine and methamphetamine on the neonate. West J Med
1989;150:436-442
Useful For: Confirming drug exposure involving amphetamines such as amphetamine and
methamphetamine, phentermine, methylenedioxyamphetamine (MDA: a metabolite of MDMA and
MDEA), methylenedioxymethamphetamine (MDMA), and methylenediaoxyethylamphetamine (MDEA)
Chain-of-custody is required whenever the results of testing could be used in a court of law. Its purpose is
to protect the rights of the individual contributing the specimen by demonstrating that it was under the
control of personnel involved with testing the specimen at all times; this control implies that the
opportunity for specimen tampering would be limited.
Reference Values:
Negative
Cutoff concentrations:
IMMUNOASSAY SCREEN
<500 ng/mL
AMPHETAMINE BY LC-MS/MS
<25 ng/mL
METHAMPHETAMINE BY LC-MS/MS
<25 ng/mL
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PHENTERMINE BY LC-MS/MS
<25 ng/mL
METHYLENEDIOXYAMPHETAMINE BY LC-MS/MS
<25 ng/mL
METHYLENEDIOXYMETHAMPHETAMINE BY LC-MS/MS
<25 ng/mL
PSEUDOEPHEDRINE/EPHEDRINE BY LC-MS/MS
<25 ng/mL reported as negative
Clinical References: 1. Baselt RC: Disposition of Toxic Drugs and Chemicals in Man. Seventh
edition. Foster City, CA. Biomedical Publications, 2004 2. Principles of Forensic Toxicology. Second
edition, Washington, DC. AACC Press, 2003 pp 385
Useful For: Confirming drug exposure involving amphetamines such as amphetamine and
methamphetamine, phentermine, methylenedioxyamphetamine (MDA),
methylenedioxymethamphetamine (MDMA), and methylenediaoxyethylamphetamine (MDEA)
Reference Values:
Negative
Cutoff concentrations:
AMPHETAMINE BY LC-MS/MS
<25 ng/mL
METHAMPHETAMINE BY LC-MS/MS
<25 ng/mL
PHENTERMINE BY LC-MS/MS
<25 ng/mL
METHYLENEDIOXYAMPHETAMINE BY LC-MS/MS
<25 ng/mL
METHYLENEDIOXYMETHAMPHETAMINE BY LC-MS/MS
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<25 ng/mL
PSEUDOEPHEDRINE/EPHEDRINE BY LC-MS/MS
<25 ng/mL reported as negative
Clinical References: 1. Baselt RC: Disposition of Toxic Drugs and Chemicals in Man. Seventh
edition. Foster City, CA. Biomedical Publications, 2004 2. Principles of Forensic Toxicology. Second
edition, Washington, DC. AACC Press, 2003 pp 385
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
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fragments. Amylase is produced by the exocrine pancreas and the salivary glands to aid in the digestion of
starch. It is also produced by the small intestine mucosa, ovaries, placenta, liver, and fallopian tubes.
Useful For: Evaluation of patients suspected of having acute pancreatitis. If ascites are present, it is
occasionally used to demonstrate pancreatic inflammation. If this is true, the level will be at least ten
times that of serum.
Interpretation: No control range has been obtained so interpretation is qualitative and thought to be
positive for pancreatitis if >1,100 U/L (10 times the serum normal range).
Reference Values:
Not applicable
Salivary amylase
18 months and older: 9-86 U/L
Total amylase
3-90 days: 0-30 U/L
3-6 months: 7-40 U/L
7-8 months: 7-57 U/L
9-11 months: 11-70 U/L
12-17 months: 11-79 U/L
18-35 months: 19-92 U/L
3-4 years: 26-106 U/L
5-12 years: 30-119 U/L
13 years and older: 30-110 U/L
Useful For: Aids in distinguishing between pseudocysts and other types of pancreatic cysts, when
used in conjunction with imaging studies, cytology, and other pancreatic cyst fluid tumor markers
Interpretation: A pancreatic cyst fluid amylase concentration of <250 U/L indicates a low risk of a
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pseudocyst and is more consistent with cystic neoplasms such as mucinous cystic neoplasms (MCN),
intraductal papillary mucinous neoplasm (IPMN), serous cystadenomas, cystic neuroendocrine tumor,
and mucinous cystadenocarcinoma. High pancreatic cyst fluid amylase values are nonspecific and occur
both in pseudocysts and some mucin-producing cystic neoplasms including MCN, IPMN, and mucinous
cystadenocarcinoma. In-house studies to verify this cutoff value showed that 94% (66/70) of
pseudocysts had a value of > or =250 U/L. Cysts with amylase levels of <250 U/L included 69% of
adenocarcinomas, 31% of intraductal papillary mucinous neoplasia, 55% of mucinous cystadenomas,
64% serous cystadenomas, and 6% of pseudocysts. Therefore, using a cutoff of <250 U/L to exclude a
pseudocyst has 94% sensitivity and 42% specificity.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Snozek CL, Mascarenhas RC, O'Kane DJ: Use of cyst fluid CEA, CA19-9,
and amylase for evaluation of pancreatic lesions. Clin Biochem 2009;42:1585-1588 2. van der Waaij LA,
van Dullemen HM, Porte RJ: Cyst fluid analysis in the differential diagnosis of pancreatic cystic lesions:
a pooled analysis. Gastrointest Endosc 2005;62:383-389 3. Khalid A, Brugge W: ACG practice guidelines
for the diagnosis and management of neoplastic pancreatic cysts. Am J Gastroenterol
2007;102:2339-2349
Useful For: Pancreatic amylase will most frequently be ordered as a serum test to detect acute
pancreatitis. If a pleural effusion occurs as a complication of acute pancreatitis, excessive amounts of
pancreatic amylase (p-amylase) in the effusion points to pancreatitis as the cause.
Interpretation: Elevated pleural effusion alpha-amylase suggests acute pancreatitis as the cause of the
effusion.
Reference Values:
Not applicable
Clinical References: Burtis CA, Ashwood ER: Clinical enzymology. In Tietz Textbook of Clinical
Chemistry. Third edition. Philadelphia, WB Saunders, 1999, pp 617-721
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accompanied by a reduced amylase clearance. Values over the normal reference interval in patients with
histories consistent with acute pancreatitis are confirmatory. Peak values are often 200 U/L or higher.
Macroamylasemia may cause small, but persistent elevations of amylase. An elevation of total serum
alpha-amylase does not specifically indicate a pancreatic disorder since the enzyme is produced by the
salivary glands, mucosa of the small intestine, ovaries, placenta, liver, and the lining of the fallopian
tubes. Two isoenzymes, pancreatic and salivary, are found in serum. Pancreatic amylase has been shown
to be more useful than total amylase when evaluating patients with acute pancreatitis.
Reference Values:
0-<24 months: 0-20 U/L
2-<18 years: 9-35 U/L
> or =18 years: 11-54 U/L
Clinical References: Sternby B, O'Brien JF, Zinsmeister AR, DiMagno EP: What is the best
biochemical test to diagnose acute pancreatitis? A prospective clinical study. Mayo Clin Proc
1996;71:1138-1144
Interpretation: Decreases in urinary amylase excretion of greater than 30% to 50%, relative to
baseline values, may be associated with acute pancreas allograft rejection. Because there is large
day-to-day variability in urinary amylase excretion following pancreas transplantation, if a significant
decrease is noted, it should be confirmed by a second collection. There is also large inter-individual
variability in urinary amylase excretion among pancreas transplant recipients. Acute rejection is usually
not established solely by changes in urinary amylase excretion, but by tissue biopsy. Levels are elevated
in acute pancreatitis (but with poor sensitivity and specificity).
Reference Values:
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No established reference values
Clinical References: 1. Tietz Textbook of Clinical Chemistry. Third edition. Edited by CA Burtis,
ER Ashwood. Philadelphia, WB Saunders Co., 1999, pp 689-698 2. Munn SR, Engen DE, Barr D, et al:
Differential diagnosis of hypo-amylasuria in pancreas allograft recipients with urinary exocrine drainage.
Transplantation 1990;49:359-362 3. Kemppainen EA, Hedstrom JI, Puolakkainen PA, et al: Rapid
measurement of urinary trypsinogen-2 as a screening test for acute pancreatitis. N Engl J Med
1997;336:1788-1793 4. Treacy J, Williams A, Bais R, et al: Evaluation of amylase and lipase in the
diagnosis of acute pancreatitis. ANZ Journal of Surgery 2001;71:577-582 5. Klassen DK, Hoen-Saric
EW, Weir MR, et al: Isolated pancreas rejection in combined kidney pancreas transplantation.
Transplantation 1996;61:974-977 6. Benedetti E, Najaran JS, Gruessener AC, et al: Correlation between
cystoscopic biopsy results and hypoamylasuria in bladder-drained pancreas transplants. Surgery
1995;118:864-872
Useful For: Assessment of acute rejection of bladder-drained pancreas transplants As an aid in the
diagnosis of acute pancreatitis
Interpretation: Decreases in urinary amylase excretion of greater than 30% to 50%, relative to
baseline values, may be associated with acute pancreas allograft rejection. Because there is large
day-to-day variability in urinary amylase excretion following pancreas transplantation, if a significant
decrease is noted, it should be confirmed by a second collection. There is also large inter-individual
variability in urinary amylase excretion among pancreas transplant recipients. Collecting a timed urine
specimen and expressing the urinary amylase level as Units excreted/hour might reduce variability and
improve test performance. However, acute rejection is usually not established solely by changes in urinary
amylase excretion, but by tissue biopsy. Urinary amylase is elevated in acute pancreatitis, but the test has
poor sensitivity and specificity.
Reference Values:
3-26 U/hour
Clinical References: 1. Tietz Textbook of Clinical Chemistry. 3rd edition. Edited by CA Burtis, ER
Ashwood. Philadelphia, WB Saunders Co., 1999, pp 689-698 2. Munn SR, Engen DE, Barr D, et al:
Differential diagnosis of hypo-amylasuria in pancreas allograft recipients with urinary exocrine drainage.
Transplantation 1990;49:359-362 3. Klassen DK, Hoen-Saric EW, Weir MR, et al: Isolated pancreas
rejection in combined kidney pancreas transplantation. Transplantation 1996;61:974-977 4. Benedetti E,
Najaran JS, Gruessener AC, et al: Correlation between cystoscopic biopsy results and hypoamylasuria in
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bladder-drained pancreas transplants. Surgery 1995;118:864-872
Reference Values:
0-30 days: 0-6 U/L
31-182 days: 1-17 U/L
183-365 days: 6-44 U/L
1-3 years: 8-79 U/L
4-17 years: 21-110 U/L
> or =18 years: 26-102 U/L
Clinical References: 1. Soldin SJ: Pediatric Reference Ranges, AACC Press, Washington DC,
Second edition. 1997 2. Tietz Textbook of Clinical Chemistry. Edited by CA Burtis, ER Ashwood. WB
Saunders Company, Philadelphia, 1999 3. Swaroop VS, Chari ST, Clain JE: Acute pancreatitis, JAMA
2004;291:2865-2868
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immunoreactivity. If a control tissue is not included on the slide, a scanned image of the relevant quality
control tissue is available upon request; contact 855-516-8404. Interpretation of this test should be
performed in the context of the patient's clinical history and other diagnostic tests by a qualified
pathologist.
Clinical References: 1. van Aalten SM, Verheij J, Terkivatan T, et al: Validation of a liver adenoma
classification system in a tertiary referral centre: implications for clinical practice. J Hepatol
2011;55(1):120-125 2. Bioulac-Sage P, Cubel G, Balabaud C, et al: Revisiting the pathology of resected
benign hepatocellular nodules using new immunohistochemical markers. Semin Liver Dis
2011;31(1):91-103 3. Bioulac-Sage P, Rebouissou S, Thomas C, et al: Hepatocellular adenoma subtype
classification using molecular markers and immunohistochemistry. Hepatology 2007;46(3):740-748
This test was developed and its performance characteristics determined by Inter Science Institute. It has
not been cleared or approved by the US Food and Drug Administration. The FDA has determined that
such clearance or approval is not necessary.
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paraffin-embedded specimens, due to its superior sensitivity and specificity.
Useful For: An aid in the identification of amyloid precursor protein present in Alzheimer disease
Interpretation: This test includes only technical performance of the stain (no pathologist
interpretation is performed). If diagnostic consultation by a pathologist is required, order 70012 /
Pathology Consultation. The positive and negative controls are verified as showing appropriate
immunoreactivity. If a control tissue is not included on the slide, a scanned image of the relevant quality
control tissue is available upon request; contact 855-516-8404. Interpretation of this test should be
performed in the context of the patient's clinical history and other diagnostic tests by a qualified
pathologist.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 150
(gene mutation or benign polymorphism). More than 90 mutations that cause TTR-associated familial AL
have now been identified within the TTR gene. Most of the mutations described to date are single base
pair changes that result in an amino acid substitution. Some of these mutations correlate with the clinical
presentation of AL. For predictive testing in cases where a familial mutation is known, testing for the
specific mutation by DNA sequence analysis (FMTT / Familial Mutation, Targeted Testing) is
recommended. These assays do not detect mutations associated with non-TTR forms of familial AL.
Therefore, it is important to first test an affected family member to determine if TTR is involved and to
document a specific mutation in the family before testing at risk individuals.
Reference Values:
An interpretive report will be provided.
Reference Values:
<1:64
Clinical References: Bakken JS, Dumler JS, Chen SM, et al: Human granulocytic ehrlichiosis in the
upper Midwest United States. A new species emerging? JAMA 1994;272:212-218
Reference Values:
IgG <1:64
IgM <1:20
Anaplasma phagocytophilum is the tick-borne agent causing Human Granulocytic Ehrlichiosis (HGE).
HGE is distinct and separate from Human Monocytic Ehrlichiosis (HME), caused by Ehrlichia
chaffeensis. Serologic crossreactivity between A. phagocytophilum and E. chaffeensis is minimal
(5-15%).
Useful For: Obtaining a rapid, expert opinion on unprocessed specimens referred by the pathologist
Interpretation: Results of the consultation are reported in a formal pathology report which includes
a description of ancillary test results (if applicable) and an interpretive comment. When the case is
completed, results may be communicated by a phone call. The formal pathology report is faxed. In our
consultative practice, we strive to bring the customer the highest quality of diagnostic pathology, in all
areas of expertise, aiming to utilize only those ancillary tests that support the diagnosis in a
cost-effective manner, and to provide a rapid turnaround time for diagnostic results.
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sensitization and clinical manifestations proceed as follows: eczema and respiratory disease (rhinitis and
bronchospasm) in infants and children less than 5 years due to food sensitivity (milk, egg, soy, and
wheat proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Clinical References: 1. Chen C, Yuan JP, Wei W, et al: Subtype classification for prediction of
prognosis of breast cancer from a biomarker panel: correlations and indications. Int J Nanomedicine
2014;9:1039-1048 2. Hobisch A, Culig Z, Radmayr C, et al: Androgen receptor status of lymph node
metastases from prostate cancer. Prostate 1996;28:129-135 3. Park S, Koo J, Park HS, et al: Expression of
androgen receptors in primary breast cancer. Ann Oncol 2010;21:488-492
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FANGL Androstanediol Glucuronide
75001 Reference Values:
Age Range
Useful For: Diagnosis and differential diagnosis of hyperandrogenism (in conjunction with
measurements of other sex-steroids). An initial workup in adults might also include total and
bioavailable testosterone (TTBS / Testosterone, Total and Bioavailable, Serum) measurements.
Depending on results, this may be supplemented with measurements of sex hormone-binding globulin
(SHBG / Sex Hormone Binding Globulin [SHBG], Serum) and other androgenic steroids (eg,
dehydroepiandrosterone sulfate [DHEA-S]). Diagnosis of congenital adrenal hyperplasia (CAH), in
conjunction with measurement of other androgenic precursors, particularly,
17-alpha-hydroxyprogesterone (OHPG) (OHPG / 17-Hydroxyprogesterone, Serum), 17
alpha-hydroxypregnenolone, DHEA-S (DHES / Dehydroepiandrosterone Sulfate [DHEA-S], Serum),
and cortisol (CORT / Cortisol, Serum). Monitoring CAH treatment, in conjunction with testosterone
(TTST / Testosterone, Total, Serum), OHPG (OHPG / 17-Hydroxyprogesterone, Serum), DHEA-S
(DHES / Dehydroepiandrosterone Sulfate [DHEA-S], Serum), and DHEA (DHEA_ /
Dehydroepiandrosterone [DHEA], Serum). Diagnosis of premature adrenarche, in conjunction with
gonadotropins (FSH / Follicle-Stimulating Hormone [FSH], Serum; LH / Luteinizing Hormone [LH],
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Serum) and other adrenal and gonadal sex-steroids and their precursors (TTBS / Testosterone, Total and
Bioavailable, Serum or TGRP / Testosterone, Total and Free, Serum; EEST / Estradiol, Serum; DHES /
Dehydroepiandrosterone Sulfate [DHEA-S], Serum; DHEA_ / Dehydroepiandrosterone [DHEA],
Serum; SHBG / Sex Hormone Binding Globulin [SHBG], Serum; OHPG / 17-Hydroxyprogesterone,
Serum).
Reference Values:
Tanner Stages Age (Years) Reference Range (ng/dL)
Stage I (prepubertal)
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Stage V 12.8-17.3 65-210 Females*
Stage I (prepubertal)
Useful For: Identifying MYC amplification to aid in the differentiation of cutaneous angiosarcomas
from atypical vascular lesions after radiotherapy An aid in the diagnosis of primary cutaneous
angiosarcoma
Interpretation: The MYC locus is reported as amplified when the MYC:D8Z2 ratio of 2.0 or greater
and demonstrates 6 or more copies of the MYC locus. A lesion with a MYC:D8Z2 ratio <2.0 or
showing a ratio of 2.0 or greater with less than 6 copies of MYC is considered to lack amplification of
the MYC locus.
Reference Values:
An interpretive report will be provided.
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FACEC Angiotensin Converting Enzyme, CSF
57824 Reference Values:
0.0 2.5 U/L
Reference Values:
> or =18 years: 8-53 U/L
The reference interval for pediatric patients may be up to 50% higher than that of adults.
Reference Values:
Up to 25 pg/mL
This test was performed using a kit that has not been cleared or approved by the FDA and is designated
as research use only. The analytic performance characteristics of this test have been determined by Inter
Science Institute. This test is not intended for diagnosis or patient management decisions without
confirmation by other medically established means.
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FANG Angiotensin II, Plasma
90428 Clinical Information: Angiotensin II is a eight amino acid peptide formed by Angiotensin
Converting Enzyme (ACE) cleavage of Angiotensin I. Angiotensin II is metabolized further to
Angiotensin III. Angiotensin II release is controlled by Renin, blood pressure, blood volume, sodium
balance and by Aldosterone concentration. Levels of Angiotensin II are increased in many types of
hypertension. Angiotensin II stimulates the release of Anti-Diuretic Hormone, ACTH, Prolactin,
Luteinizing Hormone, Oxytocin and Aldosterone. Angiotensin II increases vasoconstriction and inhibits
tubular resorption of sodium, and can increase endothelial cell growth.
Reference Values:
10 - 60 pg/mL
This test was performed using a kit that has not been cleared or approved by the FDA and is
designated as research use only. The analytic performance characteristics of this test have been
determined by Inter Science Institute. This test is not intended for diagnosis or patient management
decisions without confirmation by other medically established means.
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
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6 > or =100 Strongly positive Reference values
apply to all ages.
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
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99.99 Very Strong Positive 6 >99.99 Very Strong Positive
Reference Values:
<0.35 kU/L
Clinical References: Falini B, Tiacci E, Liso A, et al: Simple diagnostic assay for hairy cell
leukaemia by immunocytochemical detection of annexin A1 (ANXA1). Lancet 2004 Jun
5;363(9424):1869-1870
Reference Values:
<5 years: < or =250 U/mL
5-17 years < or =375 U/mL
> or =18 years: < or =300 U/mL
Clinical References: Ayoub EM, Harden E: Immune response to streptococcal antigens: diagnostic
methods. In Manual of Clinical and Laboratory Immunology. Fifth edition. Edited by NR Rose, EC de
Marco, JD Folds, et al. Washington, DC, ASM Press, 1997
Interpretation: Anti-HMGCR antibodies are usually found in association with necrotizing myopathy
related to statin therapy. However, about 30% of Anti-HMGCR positive patients with necrotizing
myopathy have never been exposed to statins. The literature suggests that false positives are extremely
rare. As a 1ab developed test (LDT), approval or clearance by the FDA is not required. This test may be
used for clinical purposes and should not be regarded as investigational or for research. Diagnosis
Number (%) Pos Polymyositis/Dermatomyositis 2/76(2.6) Systemic Lupus Erythematosis 0/30(0.0)
Primary Sjogren's Syndrome 0/30(0.0) Rheumatoid Arthritis 0/30(0.0) Systemic Sclerosis 0/30(0.0)
Normal Controls 0/47(0.0)
Reference Values:
Negative: <20
Weak Positive: 20 39
Moderate Positive: 40 59
Strong Positive: >=60
FIGA Anti-IgA
57552 Reference Values:
<99 U/mL
Patients with IgG antibodies against IgA may suffer from anaphylactoid reactions when given IVIG that
contains small quantities of IgA. In one study (Clinical Immunology 2007; 122:156) five out of eight
patients with IgG anti-IgA antibodies developed anaphylactoid reactions when IVIG was administered.
FANTI Anti-IgE
57892 Reference Values:
Normal
This ELISA measures IgG antibodies specific for IgE. A result of normal indicates that the level of IgG
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anti-IgE antibodies is similar to that seen in a population of healthy individuals. A result of elevated
indicates an increased level of IgG anti-IgE antibodies compared to healthy individuals. These
autoantibodies have been iplicated as a causative agent in autoimmune chronic urticaria and atopic
dermatitis.
Reference Values:
<13 % of basophils
Clinical References: Chronic urticaria sera increase basophil CD203c expression. Yasnowsky
KM1, Dreskin SC, Efaw B, Schoen D, Vedanthan PK, Alam R, Harbeck RJ. J Allergy Clin Immunol
2006 Jun; 117(6): 1430 4.
FCLNE Anti-Phosphatidylcholine Ab
91321 Reference Values:
Anti-Phosphatidylcholine IgA: <12.0 U/mL
Anti-Phosphatidylethanolamine IgG
<12.0 U/mL
Anti-Phosphatidylethanolamine IgM
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<12.0 U/mL
Useful For: Assessing positive pretransfusion antibody screens, transfusion reactions, hemolytic
disease of the newborn, and autoimmune hemolytic anemias
Interpretation: Specificity of alloantibodies will be stated. The patient's red blood cells will be typed
for absence of the corresponding antigen(s) or as an aid to identification in complex cases. A consultation
service is offered, at no charge, regarding the clinical relevance of red cell antibodies.
Reference Values:
Negative
If positive, antibodies will be identified and corresponding special red cell antigen typing on patient's red
blood cells will be performed. A consultation service is offered, at no charge, regarding the clinical
relevance of red cell antibodies.
Clinical References: Technical Manual. Bethesda, MD, American Association of Blood Banks
Useful For: Detection of allo- or autoantibodies directed against red blood cell antigens in the settings
of pretransfusion testing Evaluation of transfusion reactions Evaluation of hemolytic anemia
Reference Values:
Negative
If positive, antibody identification will be performed.
Clinical References: Technical Manual. 14th edition. Edited by RH Walker. Bethesda, MD,
American Association of Blood Banks, 2002, pp 379-418
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ABTIH Antibody Titer, Erythrocytes
9000 Clinical Information: Some maternal IgG alloantibodies to red blood cell antigens will cross the
placenta and cause hemolysis of antigen-positive fetal red cells. The resulting fetal anemia and
hyperbilirubinemia can be harmful or even fatal to the fetus or the newborn.
Useful For: Monitoring antibody levels during pregnancy to help assess the risk of hemolytic disease
of the newborn
Interpretation: The specificity of the maternal alloantibody will be stated. The titer result is the
reciprocal of the highest dilution at which macroscopic agglutination (1+) is observed. If the antibody
problem identified is not relevant in hemolytic disease of the newborn or if titrations are not helpful, the
titer will be canceled and will be replaced by ABID2 / Antibody Identification, Erythrocytes. A
consultation service is offered, at no charge, regarding the clinical relevance of red cell antibodies.
Reference Values:
Negative
If positive, result will be reported as the reciprocal of the highest dilution at which macroscopic
agglutination (1+) is observed.
Clinical References: Technical Manual. Bethesda, MD, American Association of Blood Banks
Sm ANTIBODIES, IgG
<1.0 U (negative)
> or =1.0 U (positive)
Reference values apply to all ages.
Jo 1 ANTIBODIES, IgG
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<1.0 U (negative)
> or =1.0 U (positive)
Reference values apply to all ages.
Interpretation: The minimum inhibitory concentration (MIC) is recorded as the lowest concentration
of antifungal agent producing complete inhibition of growth. Interpretive breakpoints are available for
Candida albicans, Candida glabrata, Candida guilliermondii, Candida krusei, Candida parapsilosis, and
Candida tropicalis for limited drugs (see tables below); the clinical relevance of testing any other
organism-drug combination remains uncertain. Agent MIC Ranges on Yeast Plate (mcg/mL) Candida
albicans Interpretations (mcg/mL) Susceptible Dose Dependent Susceptible Intermediate Resistant
Amphotericin 0.12-8 - - - - Anidulafungin 0.015-8 < or =0.25 - 0.5 > or =1 Fluconazole 0.125-256 < or =2
4 - > or =8 Itraconazole 0.015-16 - - - - Micafungin 0.008-8 < or =0.25 - 0.5 > or =1 5-Flucytosine
0.06-64 - - - - Voriconazole 0.008-8 < or =0.12 0.25-0.5 - > or =1 Caspofungin 0.008-8 < or =0.25 - 0.5 >
or =1 Posaconazole 0.008-8 - - - - Agent MIC Ranges on Yeast Plate (mcg/mL) Candida glabrata
Interpretations (mcg/mL) Susceptible Dose Dependent Susceptible Intermediate Resistant Amphotericin
0.12-8 - - - - Anidulafungin 0.015-8 < or =0.12 - 0.25 > or =0.5 Fluconazole 0.125-256 - < or =32 - > or
=64 Itraconazole 0.015-16 - - - - Micafungin 0.008-8 < or =0.06 - 0.12 > or =0.25 5-Flucytosine 0.06-64 -
- - - Voriconazole 0.008-8 - - - Caspofungin 0.008-8 < or =0.12 - 0.25 > or =1 Posaconazole 0.008-8 - - - -
Agent MIC Ranges on Yeast Plate (mcg/mL) Candida guilliermondii Interpretations (mcg/mL)
Susceptible Dose Dependent Susceptible Intermediate Resistant Amphotericin 0.12-8 - - - - Anidulafungin
0.015-8 < or =2 - 4 > or =8 Fluconazole 0.125-256 - - - - Itraconazole 0.015-16 - - - - Micafungin 0.008-8
< or =2 - 4 > or =8 5-Flucytosine 0.06-64 - - - - Voriconazole 0.008-8 - - - - Caspofungin 0.008-8 < or =2
- 4 > or =8 Posaconazole 0.008-8 - - - - Agent MIC Ranges on Yeast Plate (mcg/mL) Candida krusei
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Interpretations (mcg/mL) Susceptible Dose Dependent Susceptible Intermediate Resistant Amphotericin
0.12-8 - - - - Anidulafungin 0.015-8 < or =0.25 - 0.5 > or =1 Fluconazole 0.125-256 - - - - Itraconazole
0.015-16 - - - Micafungin 0.008-8 < or =0.25 - 0.5 > or =1 5-Flucytosine 0.06-64 - - - - Voriconazole
0.008-8 < or =0.5 1 - > or =2 Caspofungin 0.008-8 < or =0.25 - 0.5 > or =1 Posaconazole 0.008-8 - - - -
Agent MIC Ranges on Yeast Plate (mcg/mL) Candida parapsilosis Interpretations (mcg/mL) Susceptible
Dose Dependent Susceptible Intermediate Resistant Amphotericin 0.12-8 - - - - Anidulafungin 0.015-8 <
or =2 - 4 > or =8 Fluconazole 0.125-256 < or =2 4 - > or =8 Itraconazole 0.015-16 - - - - Micafungin
0.008-8 < or =2 - 4 > or =8 5-Flucytosine 0.06-64 - - - - Voriconazole 0.008-8 < or =0.12 0.25-0.5 - > or
=1 Caspofungin 0.008-8 < or =2 - 4 > or =8 Posaconazole 0.008-8 - - - - Agent MIC Ranges on Yeast
Plate (mcg/mL) Candida tropicalis Interpretations (mcg/mL) Susceptible Dose Dependent Susceptible
Intermediate Resistant Amphotericin 0.12-8 - - - - Anidulafungin 0.015-8 < or =0.25 - 0.5 > or =1
Fluconazole 0.125-256 < or =2 4 - > or =8 Itraconazole 0.015-16 - - - - Micafungin 0.008-8 < or =0.25 -
0.5 > or =1 5-Flucytosine 0.06-64 - - - - Voriconazole 0.008-8 < or =0.12 0.25-0.5 - > or =1 Caspofungin
0.008-8 < or =0.25 - 0.5 > or =1 Posaconazole 0.008-8 - - - - Please note that Candida krusei is
intrinsically resistant to fluconazole regardless of in vitro MIC result.
Reference Values:
Results reported in mcg/mL
Clinical References: Pappas PG, Rex JH, Sobel JD, et al: Guidelines for treatment of Candidiasis.
Clin Infect Dis 2004;38:161-189
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Linezolid < or =8.0 16 > or =32
Clinical References: 1. Brown-Elliott BA, Wallace RJ Jr.: Clinical and taxonomic status of
pathogenic nonpigmented or late-pigmenting rapidly growing mycobacteria. Clin Microbiol Rev 2002
October;15:716-746 2. Colombo RE, Olivier KN: Diagnosis and treatment of infections caused by
rapidly growing mycobacteria. Semin Respir Crit Care Med 2008 October;29:577-588 3. Kasperbauer
SH, DeGroote MA: The treatment of rapidly growing mycobacterial infections. Clin Chest Med 2015
March;336:67-78
S I R
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Moxifloxacin < or =1 2 > or =4
Interpretative criteria for Mycobacterium kansasii and other slowly growing mycobacteria
S R
S R
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ZMMLS Antimicrobial Susceptibility, Aerobic Bacteria, MIC
8073 Clinical Information: Antimicrobial susceptibility testing (AST) determines the minimum inhibitory
concentration or MIC of antimicrobial agents. The MIC is a measurement of the activity of an
antimicrobial agent against an organism. It is defined as the lowest concentration of an antimicrobial
agent that inhibits growth of the microorganism. Clinical breakpoints are derived from a number of data
including a) the pharmacokinetics/pharmacodynamics of an antimicrobial agent, b) the MIC distribution
of a large number of isolates, and c) clinical outcome data for a patient population treated with the
antimicrobial of interest. AST should be performed on pure culture isolates of pathogenic bacteria (or
those potentially pathogenic in special situations) grown from specimens that have been appropriately
collected so as not to confuse clinically significant isolates with normal or contaminating flora.
Susceptibility testing is indicated for any organism that contributes to an infectious process warranting
antimicrobial chemotherapy if its susceptibility cannot be reliably predicted from the organism's identity.
The MIC obtained during AST is helpful in indicating the concentration of antimicrobial agent required at
the site of infection necessary to inhibit the infecting organism. The MIC are accompanied by interpretive
categories (ie, susceptible, susceptible-dose dependent, intermediate, nonsusceptible, or resistant) when
applicable.
Useful For: Determining the in vitro susceptibility of aerobic bacteria involved in human infections
Interpretation: Refer to the "Reference Values" section for interpretation of various categories.
Reference Values:
Results are reported as minimum inhibitory concentration (MIC) in mcg/mL and as susceptible,
susceptible-dose dependent, intermediate, resistant, or nonsusceptible according to the Clinical and
Laboratory Standards Institute (CLSI) guidelines.
In some instances an interpretive category cannot be provided based on available data and the following
comment will be included: "There are no established interpretive guidelines for agents reported without
interpretations."
Susceptible (S):
The "susceptible" category implies that isolates are inhibited by the usually achievable concentrations of
antimicrobial agent when the dosage recommended to treat the site of infection is used, resulting in likely
clinical efficacy.
Intermediate (I):
The "intermediate" category includes isolates with antimicrobial agent minimum inhibitory
concentrations (MICs) that approach usually attainable blood and tissue levels, and for which response
rates may be lower than for susceptible isolates.
Note: The intermediate category implies clinical efficacy in body sites where the drugs are
physiologically concentrated or when a higher than normal dosage of a drug can be used. This category
also includes a buffer zone, which should prevent small, uncontrolled, technical factors from causing
major discrepancies in interpretations, especially for drugs with narrow pharmacotoxicity margins.
Resistant (R):
The "resistant" category implies that the isolates are not inhibited by the usually achievable
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concentrations of the agent with normal dosage schedules and/or that demonstrate MIC that fall in the
range where specific microbial resistance mechanisms are likely, and clinical efficacy of the agent against
the isolate has not been reliably shown in treatment studies.
Nonsusceptible (N):
The "nonsusceptible" category is used for isolates for which only a susceptible interpretive category has
been designated because of the absence or rare occurrence of resistant strains. Isolates for which the
antimicrobial agent MICs are above the value indicated for the susceptible breakpoint are reported as
nonsusceptible.
Note: An isolate that is interpreted as nonsusceptible does not necessarily mean that the isolate has a
resistance mechanism. It is possible that isolates with MIC above the susceptible breakpoint that lack
resistance mechanisms may be encountered within the wild-type distribution subsequent to the time the
susceptible-only breakpoint was set.
(Clinical and Laboratory Standards Institute: Performance Standards for Antimicrobial Susceptibility
Testing. 26th Informational Supplement. CLSI document M100S. Wayne, PA, 2016)
Clinical References: 1. Jorgensen JH, Ferraro MJ: Antimicrobial susceptibility testing: a review of
general principles and contemporary practices. Clin Infect Dis 2009 Dec 1;49(11):1749-1755 2. Clinical
and Laboratory Standards Institute: Performance Standards for Antimicrobial Susceptibility Testing.
26th Informational Supplement. CLSI document M100S. Wayne, PA, 2016 3. Jenkins SG, Schuetz AN:
Current concepts in laboratory testing to guide antimicrobial therapy. Mayo Clin Proc 2012
Mar;87(3):290-308
Useful For: Determining the in vitro susceptibility of anaerobic bacteria involved in human
infections
Interpretation: A "susceptible" category result and a low minimum inhibitory concentration value
indicate in vitro susceptibility of the organism to the antimicrobial tested.
Reference Values:
Results are reported as minimum inhibitory concentration (MIC) in mcg/mL and as susceptible,
intermediate, or resistant according to the Clinical and Laboratory Standards Institute (CLSI) guidelines.
Susceptible (S):
The "susceptible" category implies that isolates are inhibited by the usually achievable concentrations
of antimicrobial agent when the dosage recommended to treat the site of infection is used, resulting in
likely clinical efficacy.
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Intermediate (I):
The "intermediate" category includes isolates with antimicrobial agent minimum inhibitory
concentrations (MICs) that approach usually attainable blood and tissue levels, and for which response
rates may be lower than for susceptible isolates.
Note: The intermediate category implies clinical efficacy in body sites where the drugs are
physiologically concentrated or when a higher than normal dosage of a drug can be used. This category
also includes a buffer zone, which should prevent small, uncontrolled, technical factors from causing
major discrepancies in interpretations, especially for drugs with narrow pharmacotoxicity margins.
Resistant (R):
The "resistant" category implies that the isolates are not inhibited by the usually achievable
concentrations of the agent with normal dosage schedules and/or that demonstrate MIC that fall in the
range where specific microbial resistance mechanisms are likely, and clinical efficacy of the agent
against the isolate has not been reliably shown in treatment studies.
(Clinical and Laboratory Standards Institute: Performance Standards for Antimicrobial Susceptibility
Testing. 26th Informational Supplement. CLSI document M100S. Wayne, PA, 2016)
Useful For: Rapid, qualitative susceptibility testing of Mycobacterium tuberculosis complex isolates
growing in pure culture Affirming the initial choice of chemotherapy for Mycobacterium tuberculosis
infections Confirming the emergence of drug resistance Guiding the choice of alternate agents for therapy
for Mycobacterium tuberculosis infections
Reference Values:
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Results are reported as susceptible or resistant.
Clinical References: 1. Blumberg HM, Burman WJ, Chaisson RE, et al: American Thoracic
Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment
of tuberculosis. Am J Respir Crit Care Med 2003;167(4):603-662 2. CLSI: Susceptibility Testing of
Mycobacteria, Nocardiae, and Other Aerobic Actinomycetes; Approved Standard. CLSI document
M24-A (ISBN 1-56238-550-3). CLSI, Wayne, PA, 2003 3. Inderlied CB, Pfyffer GE: Susceptibility test
methods: Mycobacteria. In Manual of Clinical Microbiology. Eighth edition. Edited by PR Murray, EJ
Baron, JH Jorgensen, et al. Washington, DC, ASM Press, 2003, pp 1149-1177 4. LaBombardi VJ:
Comparison of the ESP and BACTEC Systems for testing susceptibilities of Mycobacterium
tuberculosis complex isolates to pyrazinamide. J Clin Microbiol 2002;40:2238-2239
Useful For: Determining the resistance of species of Nocardia and other aerobic actinomycetes to
antimicrobial agents
Interpretation: Interpretive values for susceptibility testing of Nocardia species using a broth
microdilution method. (Values expressed in mcg/mL): Antimicrobial Agent Interpretations S I R
Trimethoprim/ Sulfamethoxazole(3) < or = 2/38 - > or =4/76 Linezolid(2) < or =8 - - Ciprofloxacin < or
=1 2 > or =4 Imipenem < or =4 8 > or =16 Moxifloxacin(1,3) - - - Cefepime(3) < or =8 16 > or =32
Augmentin(3) < or =8/4 16/8 > or =32/16 Amikacin < or =8 - > or =16 Ceftriaxone(3) < or =8 16-32 >
or =64 Doxycycline < or =1 2-4 > or =8 Minocycline(3) < or =1 2-4 > or =8 Tobramycin < or =4 8 > or
=16 Clarithromycin < or =2 4 > or =8
Reference Values:
Antimicrobial Agent Concentration Range Interpretations
mcg/mL
S I R
Moxifloxacin(1,3) 0.25-8 - - -
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Clarithromycin 0.06-16 < or =2 4 > or =8 For Rhodococcus
equi, the interpretive
criteria indicated in CLSI
document M100 for
Staphylococcus aureus
are used for vancomycin
and rifampin. The
interpretive categories
should be considered
tentative pending
accumulation of further
information.
Clinical References: 1. Corti ME, Villafane-Fioti MF: Nocardiosis: a review. Int J Infect Dis
2003;7:243-250 2. Saubolle MA, Sussland D: Nocardiosis: review of clinical and laboratory experience.
J Clin Microbiol 2003;41:4497-4501 3. Brown-Elliott BA, Brown JM, Conville PS, Wallace RJ Jr:
Clinical and laboratory features of the Nocardia species based on current molecular taxonomy. Clin
Microbiol Rev 2006;19:259-282
Reference Values:
<2 ng/mL (unexposed)
3-10 ng/mL (exposed)
Clinical References: 1. Baselt R: Disposition of Toxic Drugs and Chemicals In Man. 10th edition.
2014, Biomedical Publications. Seal Beach, CA 2. Registry AfTSaD. Toxicology Profile for Antimony
and Compounds. In Services USPH, Editor;1992 3. Gebel T, Claussen K, Dunkelberg H: Human
biomonitoring of antimony. Int Arch Occup Environ Health 1998;71(3):221-224 4. Kentner M,
Leinemann M, Schaller KH, et al: External and internal antimony exposure in starter battery production.
Int Arch Occup Environ Health 1995;67(2):119-123
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FANTU Antimony, Urine
91146 Reference Values:
Reference Range: <1.0 ng/mL
Useful For: Assessment of menopausal status, including premature ovarian failure Assessing ovarian
status, including ovarian reserve and ovarian responsiveness, as part of an evaluation for infertility and
assisted reproduction protocols such as in vitro fertilization Assessing ovarian function in patients with
polycystic ovarian syndrome Evaluation of infants with ambiguous genitalia and other intersex
conditions Evaluating testicular function in infants and children Monitoring patients with antimullerian
hormone-secreting ovarian granulosa cell tumors
Interpretation: Menopausal women or women with premature ovarian failure of any cause,
including after cancer chemotherapy, have very low antimullerian hormone (AMH) levels, often below
the current assay detection limit of 0.1 ng/mL. While the optimal AMH concentrations for predicting
response to in vitro fertilization are still being established, it is accepted that AMH concentrations in the
perimenopausal to menopausal range indicate minimal to absent ovarian reserve. Depending on patient
age, ovarian stimulation is likely to fail in such patients By contrast, if serum AMH concentrations
exceed 3 ng/mL, hyper-response to ovarian stimulation may result. For these patients, a minimal
stimulation would be recommended. In patients with polycystic ovarian syndrome, AMH concentrations
may be 2- to 5-fold higher than age-appropriate reference range values. Such high levels predict
anovulatory and irregular cycles. In children with intersex conditions, an AMH result above the normal
female range is predictive of the presence of testicular tissue, while an undetectable value suggests its
absence. In boys with cryptorchidism, a measurable AMH concentration is predictive of undescended
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testes, while an undetectable value is highly suggestive of anorchia or functional failure of the
abnormally sited gonad. Granulosa cell tumors of the ovary may secrete AMH, inhibin A, and inhibin
B. Elevated levels of any of these markers can indicate the presence of such a neoplasm in a woman
with an ovarian mass. Levels should fall with successful treatment. Rising levels indicate tumor
recurrence or progression.
Reference Values:
Males
<24 months: 14-466 ng/mL
24 months-12 years: 7.4-243 ng/mL
>12 years: 0.7-19 ng/mL
Females
<24 months: <4.7 ng/mL
24 months-12 years: <8.8 ng/mL
13-45 years: 0.9-9.5 ng/mL
>45 years: <1.0 ng/mL
Clinical References: 1. Broer SL, Broekmans FJM, Laven JSE, Fauser BCJM: Anti-Mullerian
hormone: ovarian reserve testing and its potential clinical implications. Hum Reprod Update 2014
Sep-Oct;20(5):688-701 2. Dewailly D, Andersen CY, Balen A, et al: The physiology and clinical utility of
anti-Mullerian hormone in women. Hum Reprod Upd 2014;20(3):370-385
Useful For: Evaluating patients suspected of having autoimmune vasculitis, both Wegeners
granulomatosis and microscopic polyangiitis
Interpretation: Positive results for proteinase 3 (PR3) antineutrophil cytoplasmic antibodies (ANCA)
and cANCA or pANCA are consistent with the diagnosis of Wegener's granulomatosis (WG), either
systemic WG with respiratory and renal involvement or limited WG with more restricted end-organ
involvement. Positive results for MPO ANCA and pANCA are consistent with the diagnosis of
autoimmune vasculitis including microscopic polyangiitis (MPA) or pauci-immune necrotizing
glomerulonephritis. A positive result for PR3 ANCA or MPO ANCA has been shown to detect 89% of
patients with active WG or MPA (with or without renal involvement) with fewer than 1% false-positive
results in patients with other diseases.(1)
Reference Values:
MYELOPEROXIDASE ANTIBODIES, IgG
<0.4 U (negative)
0.4-0.9 U (equivocal)
> or =1.0 U (positive)
Reference values apply to all ages.
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Reference values apply to all ages.
Clinical References: 1. Russell KA, Wiegert E, Schroeder DR, et al: Detection of anti-neutrophil
cytoplasmic antibodies under actual clinical testing conditions. Clin Immunol 2002
May;103(2):196-203 2. Specks U, Homburger HA, DeRemee RA: Implications of cANCA testing for
the classifications of Wegner's Granulomatosis: performance of different detection systems. Adv Exp
Med Biol 1993;336:65-70
Reference Values:
< or =1.0 U (negative)
1.1-2.9 U (weakly positive)
3.0-5.9 U (positive)
> or =6.0 U (strongly positive)
Reference values apply to all ages.
Clinical References: 1. Kavanaugh A, Tomar R, Reveille J, et al: Guidelines for use of the
antinuclear antibody test and tests for specific autoantibodies to nuclear antigens. Pathol Lab Med
2000;124:71-81 2. Homburger HA, Cahen YD, Griffiths J, Jacob GL: Detection of antinuclear
antibodies: comparative evaluation of enzyme immunoassay and indirect immunofluorescence methods.
Arch Pathol Lab Med 1998;122:993-999
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diseases, both systemic and organ-specific. They are particularly common in the systemic rheumatic
diseases, which include lupus erythematosus (LE), discoid LE, drug-induced LE, mixed connective
tissue disease, Sjogren syndrome, scleroderma (systemic sclerosis), CREST (calcinosis, Raynaud
phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) syndrome,
polymyositis/dermatomyositis, and rheumatoid arthritis.(1) The diagnosis of a systemic rheumatic
disease is based primarily on the presence of compatible clinical signs and symptoms. The results of
tests for autoantibodies including ANA and specific autoantibodies are ancillary. Additional diagnostic
criteria include consistent histopathology or specific radiographic findings. Although individual
systemic rheumatic diseases are relatively uncommon, a great many patients present with clinical
findings that are compatible with a systemic rheumatic disease and large numbers of tests for ANA are
ordered to eliminate the possibility of a systemic rheumatic disease.
Reference Values:
<1:80 (Negative)
Clinical References: 1. Kavanaugh A, Tomar R, Reveille J, et al: Guidelines for use of the
antinuclear antibody test and tests for specific autoantibodies to nuclear antigens. Pathol Lab Med
2000;124:71-81 2. Homburger HA, Cahen YD, Griffiths J, Jacob GL: Detection of antinuclear antibodies:
comparative evaluation of enzyme immunoassay and indirect immunofluorescence methods. Arch Pathol
Lab Med 1998;122:993-999
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Reference Values:
<5 years: < or =70 IU/mL
5-17 years: < or =640 IU/mL
> or =18 years: < or =530 IU/mL
Interpretation: Antithrombin deficiencies due to inherited causes are much less common than those
due to acquired causes (see Clinical Information). Diagnosis or hereditary deficiency requires clinical
correlation, with the prospect of repeat testing (including antithrombin antigen assay) and family studies
(with appropriate counseling). DNA-based diagnostic testing may be helpful, but is not readily
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available. The clinical significance (thrombotic risk) of acquired antithrombin deficiency is not well
established, but accumulating information suggests possible benefit of antithrombin replacement
therapy in carefully selected situations.(4) Antithrombin deficiency, acquired or congenital, may
contribute to the phenomenon of "heparin therapy resistance" (requirement of larger heparin doses than
expected for achievement of therapeutic anticoagulation responses). However, it may more often have
other pathophysiology, such as "acute-phase" elevation of coagulation factor VIII or plasma
heparin-binding proteins. Increased antithrombin activity is of unknown hemostatic significance. Direct
factor Xa inhibitors, rivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Savaysa) may falsely
elevate the antithrombin activity and mask a diagnosis of antithrombin deficiency.
Reference Values:
> or =6 months-adults: 80-130%
Normal, full-term newborn infants may have decreased levels (> or =35-40%), which reach adult levels
by 90 days postnatal.*
Healthy, premature infants (30-36 weeks gestation) may have decreased levels which reach adult levels
by 180 days postnatal.*
*See Pediatric Hemostasis References in Coagulation Studies in Special Instructions.
Clinical References: 1. Lane DA, Olds RJ, Thein SL: Antithrombin and its deficiency. In
Haemostasis and Thrombosis. Third edition. Edited by AL Bloom, CD Forbes, DP Thomas, et al:
London, England, Churchill Livingstone, 1994, pp 655-670 2. Lane DA, Bayston T, Olds RJ, et al:
Antithrombin mutation database: For the Plasma Coagulation Inhibitors Subcommittee of the Scientific
and Standardization Committee of the International Society on Thrombosis and Haesmostasis. Thromb
Haemost 1997;77:197-211 3. Young G, Dricsoll MC: Coagulation abnormalities in the
carbohydrate-deficient glycoprotein syndrome: case report and review of the literature. Am J Hematol
1999;60:66-69 4. Mammen EF: Antithrombin: its physiological importance and role in DIC. Semin
Thromb Haemost 1998;24:19-25
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useful as an adjunct in the diagnosis and management of CDGS. Acquired deficiency of antithrombin is
much more common than hereditary deficiency. Acquired deficiency can occur due to: -Heparin therapy
(catalysis of antithrombin consumption) -Intravascular coagulation and fibrinolysis (ICF) or disseminated
intravascular coagulation (DIC), and other consumptive coagulopathies -Liver disease (decreased
synthesis and/or increased consumption) -Nephrotic syndrome (urinary protein loss) -L-asparaginase
chemotherapy (decreased synthesis) -Other conditions(1) In general, the clinical implications (thrombotic
risk) of antithrombin deficiency in these disorders are not well defined, although antithrombin
replacement in severe DIC/IFC is being evaluated.(4) Assay of antithrombin activity may be of diagnostic
or prognostic value in some acquired deficiency states.
Useful For: Assessing abnormal results of the antithrombin activity assay (ATTF / Antithrombin
Activity, Plasma), which is recommended as the primary (screening) antithrombin assay Diagnosing
antithrombin deficiency, acquired or congenital, in conjunction with measurement of antithrombin
activity As an adjunct in the diagnosis and management of carbohydrate-deficient glycoprotein
syndromes
Interpretation: Hereditary antithrombin deficiency is much less common than acquired deficiency.
Diagnosis of hereditary deficiency requires clinical correlation, testing of both antithrombin activity and
antithrombin antigen, and may be aided by repeated testing and by family studies. DNA-based
diagnostic testing may be helpful, but is generally not readily available. Acquired antithrombin
deficiency may occur in association with a number of conditions (see Clinical Information). The clinical
significance (thrombotic risk) of acquired antithrombin deficiency is not well established, but
accumulating information suggests possible benefit of antithrombin replacement therapy in carefully
selected situations.(4) Increased antithrombin activity has no definite clinical significance.
Reference Values:
Adults: 80-120%
Normal, full-term newborn infants may have decreased levels (> or =35-40%) which reach adult levels
by 180 days postnatal.*
Healthy, premature infants (30-36 weeks gestation) may have decreased levels which reach adult
levels by 180 days postnatal.*
*See Pediatric Hemostasis References in Coagulation Studies in Special Instructions.
Clinical References: 1. Bock SC: Antithrombin III and heparin cofactor II. In Hemostasis and
Thrombosis. Fourth edition. Edited by RW Colman, J Hirsh, VJ Marder, et al. Philadelphia, Lippencott
Williams and Wilkins, 2001, pp 321-333 2. Viazzer H: Hereditary and acquired antithrombin
deficiency. Semin Thromb Hemost 1999;25(3):257-263 3. Conrad J: Antithrombin activity and antigen.
In Laboratory Techniques in Thrombosis-A Manual. Second edition. Boston, MA, Kluwer Academic
Publishers, 1999, pp 121-128 4. Lane DA, Bayston T, Olds RJ, et al: Antithrombin mutation database:
update. For the Plasma Coagulation Inhibitors Subcommittee of the Scientific and Standardization
Committee of the International Society on Thrombosis and Haemostasis. Thromb Haemost 1997
January;77(1):197-211
Useful For: Confirmation of familial adenomatous polyposis (FAP) diagnosis for patients with clinical
features
Interpretation: All detected alterations are evaluated according to American College of Medical
Genetics recommendations.(1) Variants are classified based on known, predicted, or possible
pathogenicity and reported with interpretive comments detailing their potential or known significance.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for
standards of interpretation and reporting of sequence variations: revisions 2007. Genet Med
2008;10(4):294-300 2. American Society of Clinical Oncology. American Society of Clinical Oncology
policy statement update: genetic testing for cancer susceptibility Clin Oncol. 2003;21:2397-2406 3. Half
E, Bercovich D, Rozen P: Familial adenomatous polyposis. Orphanet J Rare Dis. 2009 Oct 12;4:22 4.
Croner RS, Brueckl WM, Reingruber B, et al: Age and manifestation related symptoms in familial
adenomatous polyposis. BMC Cancer 2005 Mar 2;5:24
Interpretation: All detected alterations are evaluated according to American College of Medical
Genetics recommendations.(1) Variants are classified based on known, predicted, or possible
pathogenicity and reported with interpretive comments detailing their potential or known significance.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for
standards of interpretation and reporting of sequence variations: revisions 2007. Genet Med
2008;10(4):294-300 2. Eriksson M, Schonland S, Yumlu S, et al: Hereditary apolipoprotein
AI-associated amyloidosis in surgical pathology specimens: identification of three novel mutations in
the APOA1 gene. J Mol Diagn 2009;11(3):257-262 3. Benson MD: Ostertage revisited: The inherited
systemic amyloidoses without neuropathy. Amyloid 2005:12(2):75-80 4. von Eckardstein A:
Differential diagnosis of familial high density lipoprotein deficiency syndromes. Atherosclerosis
2006;186:231-239 5. Shiller SM, Dogan A, Highsmith WE: Laboratory methods for the diagnosis of
hereditary amyloidoses. In Amyloidosis-Mechanisms and Prospects for Therapy. Edited by S
Sarantseva. InTech 2011, pp 101-120
Interpretation: All detected alterations are evaluated according to American College of Medical
Genetics recommendations.(1) Variants are classified based on known, predicted, or possible
pathogenicity and reported with interpretive comments detailing their potential or known significance.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for
standards of interpretation and reporting of sequence variations: revisions 2007. Genet Med
2008;10(4):294-300 2. Benson MD. Ostertage revisited: The inherited systemic amyloidoses without
neuropathy. Amyloid 2005;12(2):75-80 3. Benson MD, Liepnieks JJ, Yazaki M, et al: A new human
hereditary amyloidosis: The result of a stop-codon mutation in the Apolipoprotein AII gene. Genomics
2001;72:272-277 4. Yazaki M, Liepnieks JJ, Yamashita T, et al: Renal amyloidosis caused by a novel
stop-codon mutation in the apolipoprotein A-II gene. Kidney Int 2001;60:1658-1665 5. Yazaki M,
Liepnieks JJ, Barats MS, et al: Hereditary systemic amyloidosis associated with a new apolipoprotein AII
stop-codon mutation Stop78Arg. Kidney Int 2003;64:11-16
Useful For: Assessment of residual risk in patients at target non-HDL-C (or LDL-C) Follow-up studies
in individuals with non-HDL-C (or LDL-C) values inconsistent with risk factors or clinical presentation
Definitive studies of cardiac risk factors in individuals with significant family histories of coronary artery
disease or other increased risk factors
Interpretation: An elevated apolipoprotein B (ApoB) level confers increased risk of coronary artery
disease and can be used as a therapeutic target analogous to non-HDL-C and LDL-C. Risk Category
Therapeutic Target: ApoB Non-HDL-C LDL-C Moderate to High <90 mg/dL <130 mg/dL <100 mg/dL
Very High <80 mg/dL <100 mg/dL <70 mg/dL Extremely low values of ApoB (<48 mg/dL) are related to
malabsorption of food lipids and can lead to polyneuropathy. A reduced apolipoprotein A1 (ApoA1) level
confers an increased risk of coronary artery disease. Identification of an ApoA1 <25 mg/dL may be
helpful in the detection of a genetic disorder such as Tangier disease. An elevated ApoB:ApoA1 ratio
confers an increased risk of coronary artery disease.
Reference Values:
Age Apolipoprotein A (mg/dL) Apolipoprotein B (mg/dL) Apolipoprotein B/A1 ratio
2-17 years Low: low: 115-120 Acceptable: Acceptable: high: 90-109 High:
>120 > or =110
>18 years > or =120 Desirable: Desirable: 90-99 Lower Risk: Risk: 0.7-0.9
Borderline high: 100-119 High: Higher Risk: >0.9 Females
120-139 Very high: > or =140
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Not established Not established Not established
2-17 years Low: low: 115-120 Acceptable: Acceptable: high: 90-109 High:
>120 > or =110
>18 years > or =140 Desirable: Desirable: 90-99 Lower Risk: Risk: 0.6-0.8
Borderline high: 100-119 High: Higher Risk: >0.8
120-139 Very high: > or =140
Clinical References: 1. Reiner Z, Catapano AL, De Backer G, et al: ESC/EAS Guidelines for the
management of dyslipidaemias: The task force for the management of dyslipidaemias of the European
Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J
2011;32(14):1769-1818 2. McQueen MJ, Hawken S, Wang X, et al: Lipids, lipoproteins, and
apolipoproteins as risk markers of myocardial infarction in 52 countries (the INTERHEART study): a
case-control study. Lancet 2008;372:224-233 3. Thompson A, Danesh J: Associations between
apolipoprotein B, apolipoprotein AI, the apolipoprotein B/AI ratio and coronary heart disease: a
literature-based meta-analysis of prospective studies. J Intern Med 2006;259:481-492 4. Jacobson TA, Ito
MK, Maki KC, et al: National Lipid Association recommendations for patient-centered management of
dyslipidemia: Part 1-executive summary. J Clin Lipidol 2014 Sep-Oct;8(5):473-488 5. Expert panel on
integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary
report. Pediatrics 2011 Dec;128 Suppl 5:S213-S256
Useful For: Evaluation of risk for atherosclerotic cardiovascular disease Helpful to aid in the
detection of Tangier disease
Reference Values:
Age Apolipoprotein A (mg/dL)
Not established
Not established
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>18 years > or =140
Clinical References: 1. Sorci-Thomas MG, Thomas MJ: Why Targeting HDL Should Work as a
Therapeutic Tool, but Has Not. J Cardiovasc. Pharmacol 2013;62:239-246 2. Di Angelantonio E,
Sarwar N, Perry P, et al: Emerging Risk Factors Collaboration. Major lipids, apolipoproteins, and risk
of vascular disease. JAMA 2009;302:1993-2000 3. McQueen MJ, Hawken S, Wang X, et al: Lipids,
lipoproteins, and apolipoproteins as risk markers of myocardial infarction in 52 countries (the
INTERHEART study): a case control study. Lancet 2008;372:224-233 4. Sung KC, Wild SH, Byrne
CD: Controlling for apolipoprotein A-I concentrations changes the inverse direction of the relationship
between high HDL-C concentration and a measure of pre-clinical atherosclerosis. Atherosclerosis
2013;231:181-186 5. Boekholdt SM, Arsenault BJ, Hovingh GK, et.al: Levels and Changes of HDL
Cholesterol and Apolipoprotein A-I in Relation to Risk of Cardiovascular Events Among Statin-Treated
Patients: A Meta-Analysis. Circulation 2013;128:1504-1512
Useful For: Assessment of residual risk in patients at target non high-density lipoprotein-cholesterol
(HDL-C) (or low-density lipoprotein-cholesterol: LDL-C) Follow-up studies in individuals with
non-HDL-C (or LDL-C) values inconsistent with risk factors or clinical presentation Definitive studies of
cardiac risk factors in individuals with significant family histories of coronary artery disease or other
increased risk factors Confirmation of suspected abetalipoproteinemia or hypobetalipoproteinemia
Interpretation: Elevated ApoB confers increased risk of coronary artery disease ApoB can be used as
a therapeutic target analogous to non-HDL-C and LDL-C. Risk Category Therapeutic Target: ApoB
Non-HDL-C LDL-C Moderate to High <90 mg/dL <130 mg/dL <100 mg/dL Very High <80 mg/dL <100
mg/dL <70 mg/dL Extremely low values of ApoB (<48 mg/dL) are related to malabsorption of food lipids
and can lead to polyneuropathy.
Reference Values:
Age Apolipoprotein B (mg/dL)
Not established
>18 years Desirable: Desirable: 90-99 Borderline high: 100-119 High: 120-139 Very high: > or =140
Clinical References: 1. Cole TG, Contois JH, Csako G, et al: Association of apolipoprotein B and
nuclear magnetic resonance spectroscopy-derived LDL particle number with outcomes in 25 clinical
studies: assessment by the AACC Lipoprotein and Vascular Diseases Division Working Group on best
practices. Clin Chem 2013;59:752-770 2. Sierra-Johnson J, Fisher RM, Romero-Corral A, et al:
Concentration of apolipoprotein B is comparable with the apolipoprotein B/apolipoprotein A-I ratio and
better than routine clinical lipid measurements in predicting coronary heart disease mortality: findings
from a multi-ethnic US population. Eur Heart J 2009;30(6):710-717 3. Steffen BT, Guan W, Remaley AT,
et al: Use of lipoprotein particle measures for assessing coronary heart disease risk Post-American Heart
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 186
Association / American College of Cardiology Guidelines: The Multi-Ethnic Study of Atherosclerosis.
Arterioscler Thromb Vasc Biol 2015;35:448-454 4. Thompson A, Danesh J: Associations between
apolipoprotein B, apolipoprotein AI, the apolipoprotein B/AI ratio and coronary heart disease: a
literature-based meta-analysis of prospective studies. J Intern Med 2006;259:481-492 5. Mora S, Buring
JE, Ridker PM: Discordance of low-density lipoprotein (LDL) cholesterol with alternative LDL-related
measures and future coronary events. Circulation 2014;129:553-561 6. Pencina MJ, D'Agostino RB,
Zdrojewski T, et al: Apolipoprotein B improves risk assessment of future coronary heart disease in the
Framingham Heart Study beyond LDL-C and non-HDL-C. Eur J Prev Cardiol 2015;epub ahead of print 7.
Thanassoulis G, Williams K, Ye K, et al: Relations of change in plasma levels of LDL-C, non-HDL-C
and apoB with risk reduction from statin therapy: a meta-analysis of randomized trials. J Am Heart Assoc
2014;3:e000759 8. Jacobson TA, Ito MK, Maki KC, et al: National Lipid Association recommendations
for patient-centered management of dyslipidemia: Part 1-executive summary. J Clin Lipidol 2014
Sep-Oct;8(5):473-488 9. Expert panel on integrated guidelines for cardiovascular health and risk
reduction in children and adolescents: summary report. Pediatrics 2011 Dec;128 Suppl 5:S213-S256 10.
Contois JH, McConnell JP, Sethi AA, et al: Apolipoprotein B and Cardiovascular Disease Risk: Position
Statement from the AACC Lipoproteins and Vascular Diseases Division Working Group on Best
Practices. Clinical Chemistry 2009:55:3:407-419
Useful For: Determining the specific apolipoprotein E (APOE) genotypes in patients with type III
hyperlipoproteinemia APOE genotyping has been used to assess susceptibility for Alzheimer disease.
However, the use of APOE analysis for predictive testing for Alzheimer disease is not currently
recommended by the American College of Medical Genetics due to limited clinical utility and poor
predictive value.
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dysbetalipoproteinemia: Clinical, biochemical, and genetic aspects. Semin Vasc Med
2004;4(3):249-257 2. Utermann G: Morgagni lecture: genetic polymorphism of apolipoprotein E-impact
on plasma lipoprotein metabolism In Diabetes, Obesity and Hyperlipidemias. Edited by G Crepaldi, A
Tiengo, G Baggio. Amsterdam. Elsevier, 1985, pp 1-28 3. Elosua R, Ordovas JM, Cupples LA, et al:
Association of APOE genotype with carotid atherosclerosis in men and women: the Framingham Heart
Study. J Lipid Res 2004;45(10):1868-1875 4. Poirier J, Davignon J, Bouthillier D, et al: Apolipoprotein
E polymorphism and Alzheimers disease. Lancet 1993;342: 697-699 5. Farrer L, Cupples A,
Haines J, et al: Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype
and Alzheimer disease: a meta-analysis. JAMA 1997;278:1349-1356 6. Goldman JS, Hahn SE, Catania
JW, et al: Genetic counseling and testing for Alzheimer disease: joint practice guidelines of the
American College of Medical Genetics and the National Society of Genetic Counselors. Genet Med
2011;13(6):597-605 7. American College of Medical Genetics and Genomics 2015 July 10. Available
at: www.choosingwisely.org/societies/american-college-of-medical-genetics-and-genomics/
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical utility
of food-specific IgG tests has not been established. These tests can be used in special clinical situations to
select foods for evaluation by diet elimination and challenge in patients who have food-related
complaints. It should be recognized that the presence of food-specific IgG alone cannot be taken as
evidence of food allergy and only indicates immunologic sensitization by the food allergen in question.
This test should only be ordered by physicians who recognize the limitations of the test.
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
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1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 189
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Aiding the diagnosis of arboviral (California [LaCrosse], St. Louis encephalitis, Eastern
equine encephalitis, and Western equine encephalitis virus) encephalitis
Interpretation: In patients infected with these or related viruses, IgG antibody is generally detectable
with in 1 to 3 weeks of onset, peaking within 1 to 2 months, and declining slowly thereafter. IgM class
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antibody is also reliably detected within 1 to 3 weeks of onset, peaking and rapidly declining within 3
months. A single serum specimen IgG > or =1:10 indicates exposure to the virus. Results from a single
serum specimen can differentiate early (acute) infection from past infection with immunity if IgM is
positive (suggests acute infection). A 4-fold or greater rise in IgG antibody titer in acute and convalescent
sera indicate recent infection. In the United States, it is unusual for any patient to show positive reactions
to more than 1 of the arboviral antigens, although Western equine encephalitis and Eastern equine
encephalitis antigens will show a noticeable cross-reactivity.
Reference Values:
CALIFORNIA VIRUS (La CROSSE) ENCEPHALITIS ANTIBODY
IgG: <1:10
IgM: <1:10
Reference values apply to all ages.
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involvement is demonstrated in only a minority of infected individuals, and is more abrupt and more
severe than with other arboviruses, with children being more susceptible to severe disease. Fatality rates
are approximately 70%. St. Louis Encephalitis (SLE): Areas or outbreaks of SLE since 1933 have
involved the western United States, Texas, the Ohio-Mississippi Valley, and Florida. The vector of
transmission is the mosquito. Peak incidence occurs in summer and early autumn. Disease onset is
characterized by generalized malaise, fever, chills, headache, drowsiness, nausea, and sore throat or
cough followed in 1 to 4 days by meningeal and neurologic signs. The severity of illness increases with
advancing age; persons over 60 years have the highest frequency of encephalitis. Symptoms of
irritability, sleeplessness, depression, memory loss, and headaches can last up to 3 years. Western
Equine Encephalitis (WEE): The virus that causes WEE is widely distributed throughout the United
States and Canada; disease occurs almost exclusively in the western states and Canadian provinces. The
relative absence of the disease in the eastern United States probably reflects a paucity of the vector
mosquito species, Culex tarsalis, and possibly a lower pathogenicity of local virus strains. The disease
usually begins suddenly with malaise, fever, and headache, often with nausea and vomiting. Vertigo,
photophobia, sore throat, respiratory symptoms, abdominal pain, and myalgia are also common. Over a
few days, the headache intensifies; drowsiness and restlessness may merge into a coma in severe cases.
In infants and children, the onset may be more abrupt than for adults. WEE should be suspected in any
case of febrile CNS disease from an endemic area. Infants are highly susceptible to CNS disease and
about 20% of cases are under 1 year of age. There is an excess of males with WEE clinical encephalitis,
averaging about twice the number of infections detected in females. After recovery from the acute
disease, patients may require from several months to 2 years to overcome the fatigue, headache, and
irritability. Infants and children are at a higher risk of permanent brain damage after recovery than
adults. Infections with arboviruses can occur at any age. The age distribution depends on the degree of
exposure to the particular transmitting arthropod relating to age, sex, and occupational, vocational, and
recreational habits of the individuals. Once humans have been infected, the severity of the host response
may be influenced by age. WEE tends to produce the most severe clinical infections in young persons
and SLE in older persons. Serous California (LaCrosse) virus infections primarily involve children,
especially boys. Adult males exposed to California viruses have high-prevalence rates of antibody but
usually show no serious illness. Infections among males is primarily due to working conditions and
sports activities taking place where the vector is present.
Useful For: Aiding the diagnosis of arboviral (California [LaCrosse], St. Louis, Eastern equine, and
Western equine virus) encephalitis
Reference Values:
CALIFORNIA VIRUS (La CROSSE) ENCEPHALITIS ANTIBODY
IgG: <1:10
IgM: <1:10
Reference values apply to all ages.
Clinical References: 1. Radwan NA, Ahmed NS: The diagnostic value of arginase-1
immunostaining in differentiating hepatocellular carcinoma from metastatic carcinoma and
cholangiocarcinoma as compared to HepPar-1. Diagn Pathol 2012;7:149 2. Timek DT, Shi J, Liu H, Lin
F: Arginase-1, HepPar-1, and Glypican-3 are the most effective panel of markers in distinguishing
hepatocellular carcinoma from metastatic tumor on fine-needle aspiration specimens. Am J Clin Pathol
2012;138(2):203-210 3. Fujiwara M, Kwok S, Yano H, Pai RK: Arginase-1 is a more sensitive marker
of hepatic differentiation than HepPar-1 and glypican-3 in fine-needle aspiration biopsies. Cancer
Cytopathol 2012;120(4):230-237 4. Yan BC, Gong C, Song J, et al: Arginase-1: a new
immunohistochemical marker of hepatocytes and hepatocellular neoplasms. Am J Surg Pathol
2010;34(8):1147-1154
Reference Values:
Adults: <4.3 pg/mL
Reference values were determined on platelet-poor EDTA plasma from individuals fasting no longer
than overnight.
Clinical References: Robertson GL: Antidiuretic hormone. Normal and disordered function.
Endocrinol Metab Clin North Am 2001 September;30(3):671-694
Expected steady state plasma levels in patients receiving recommended daily dosages: 109.0 - 585.0
ng/mL
Reference Values:
Units: mg/L
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ARVGP Arrhythmogenic Cardiomyopathy Multi-Gene Panel, Blood
63160 Clinical Information: The cardiomyopathies are a group of disorders characterized by disease of
the heart muscle. Cardiomyopathy can be caused by inherited, genetic factors, or by nongenetic
(acquired) causes such as infection or trauma. When the presence or severity of the cardiomyopathy
observed in a patient cannot be explained by acquired causes, genetic testing for the inherited forms of
cardiomyopathy may be considered. Overall, the cardiomyopathies are some of the most common
genetic disorders. The inherited forms of cardiomyopathy include hypertrophic cardiomyopathy (HCM),
dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC or AC), and
left ventricular noncompaction (LVNC). Arrhythmogenic right ventricular dysplasia (ARVD or AC), is
characterized by breakdown of the myocardium and replacement of the muscle tissue with fibrofatty
tissue, resulting in an increased risk of arrhythmia and sudden death. The incidence of ARVC is
approximately 1 in 1,000 to 1 in 2,500. Age of onset and severity are variable, but symptoms typically
develop in adulthood. ARVC is present in 4% to 22% of athletes with sudden cardiac death, and there is
some debate whether high-intensity endurance exercise may cause development of ARVC. ARVC is
typically considered a disease of the desmosome, the structure that attaches heart muscle cells to one
another. The desmosome provides strength to the muscle tissue and plays a role in signaling between
neighboring cells. Variants in the genes associated with ARVC disrupt this function, causing
detachment and death of myocardial cells when the heart muscle is under stress. Damaged myocardium
is replaced with fat and scar tissue, eventually leading to structural and electrical abnormalities that can
lead to arrhythmia. Inheritance of ARVC typically follows an autosomal dominant pattern of
inheritance, and variants in DSC2, DSP, and PKP2 account for approximately half of the variants
identified in ARVC. However, simultaneous testing of all known ARVC genes is recommended due to
the potential for compound heterozygosity (biallelic variants on the same gene) or digenic
heterozygosity (variants in 2 different genes). See table for details regarding the genes tested by this
panel and associated diseases. Genes included in the Arrhythmogenic Cardiomyopathy Multi-Gene
Panel Gene Protein Inheritance Disease Association DES Desmin AD, AR DCM, ARVC, myofibrillar
myopathy, RCM with AV block, neurogenic scapuloperoneal syndrome Kaeser type, LGMD DSC2
Desmocollin AD, AR ARVC, ARVC + skin and hair findings DSG2 Desmoglein AD ARVC DSP
Desmoplakin AD, AR ARVC, DCM, Carvajal syndrome JUP Junction plakoglobin AD, AR ARVC,
Naxos disease LMNA Lamin A/C AD, AR DCM, EMD, LGMD, congenital muscular dystrophy,
ARVC (see OMIM for full listing) PKP2 Plakophilin 2 AD ARVC RYR2 Ryanodine receptor 2 AD
ARVC, CPVT, LQTS TMEM43 Transmembrane protein 43 AD ARVC, EMD TTN Titin AD, AR
HCM, DCM, ARVC, myopathy Abbreviations: Hypertrophic cardiomyopathy (HCM), dilated
cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), restrictive
cardiomyopathy (RCM), limb-girdle muscular dystrophy (LGMD), Emory muscular dystrophy (EMD),
catecholaminergic polymorphic ventricular tachycardia (CPVT), long QT syndrome (LQTS), autosomal
dominant (AD), autosomal recessive (AR)
Useful For: Providing a comprehensive genetic evaluation for patients with a personal or family
history suggestive of hereditary arrhythmogenic right ventricular cardiomyopathy (ARVC or AC)
Establishing a diagnosis of ARVC or AC, and in some cases, allowing for appropriate management and
surveillance for disease features based on the gene involved Identifying a pathogenic variant within a
gene known to be associated with disease that allows for predictive testing of at-risk family members
Interpretation: Evaluation and categorization of variants is performed using the most recent
published American College of Medical Genetics and Genomics (ACMG) recommendations as a
guideline. Variants are classified based on known, predicted, or possible pathogenicity and reported
with interpretive comments detailing their potential or known significance. Multiple in silico evaluation
tools may be used to assist in the interpretation of these results. The accuracy of predictions made by in
silico evaluation tools is highly dependent upon the data available for a given gene, and predictions
made by these tools may change over time. Results from in silico evaluation tools should be interpreted
with caution and professional clinical judgment.
Reference Values:
An interpretive report will be provided.
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Ardinger, et al. University of Washington, Seattle. 1993-2014. Updated 2014 Jan 9. Available at
http://www.ncbi.nlm.nih.gov/books/NBK1131/ 2. Ackerman MJ, Priori SG, Willems S, et al:
HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and
cardiomyopathies. Heart Rhythm 2011;8:1308-1339 3. Taylor M, Graw S, Sinagra G, et al: Genetic
variation in titin in arrhythmogenic right ventricular cardiomyopathy-overlap syndromes. Circulation
2011;124.9:876-885
Useful For: Second-tier test for confirming a diagnosis of metachromatic leukodystrophy (MLD) based
on clinical findings and low ARSA activity levels Carrier testing when there is a family history of MLD,
but disease-causing mutations have not been previously identified
Interpretation: All detected alterations are evaluated according to American College of Medical
Genetics recommendations.(1) Variants are classified based on known, predicted, or possible
pathogenicity and reported with interpretive comments detailing their potential or known significance.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for
standards of interpretation and reporting of sequence variations: revisions 2007. Genet Med
2008;10(4):294-300 2. Biffi A, Cesani M, Fumagalli F, et al: Metachromatic leukodystrophy-mutation
analysis provides further evidence of genotype-phenotype correlation. Clin Genet 2008 Oct;74(4):349-357
3. Gieselmann V, Krageloh-Mann I: Metachromatic leukodystrophy-an update. Neuropediatrics 2010
Feb;41(1):1-6, Epub 2010 Jun 22 4. Kreysing J, von Figura K, Gieselmann V: Structure of the
arylsulfatase A gene. Eur J Biochem 1990 Aug 17;191(3):627-631 5. Polten A, Fluharty AL, Fluharty CB,
et al: Molecular basis of different forms of metachromatic leukodystrophy. N Engl J Med 1991 Jan
3;324(1):18-22
Reference Values:
INORGANIC ARSENIC
0-24 mcg/specimen
Reference values apply to all ages.
Clinical References: Caldwell KL, Jones RL, Verdon CP, et al: Levels of urinary total and
speciated arsenic in the US population: National Health and Nutrition Examination Survey 2003-2004. J
Expo Sci Environ Epidemiol 2009;19:59-68
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Interpretation: The quantitative reference range for fractionated arsenic applies only to the inorganic
forms. Concentrations > or =25 mcg inorganic arsenic per specimen are considered toxic. There is no
limit to the normal range for the organic forms of arsenic, since they are not toxic and normally present
after consumption of certain food types. For example, a typical finding in a urine specimen with total
24-hour excretion of arsenic of 350 mcg/24 hours is >95% is present as the organic species from a dietary
source, and <5% present as the inorganic species. This would be interpreted as indicating the elevated
total arsenic was due to ingestion of the nontoxic form of arsenic, usually found in food. A normal value
for blood arsenic does not exclude a finding of an elevated urine inorganic arsenic, due to the very short
half-life of blood arsenic.
Reference Values:
INORGANIC ARSENIC
0-24 mcg/L
Reference values apply to all ages.
Clinical References: Caldwell KL, Jones RL, Verdon CP, et al: Levels of urinary total and speciated
arsenic in the US population: National Health and Nutrition Examination Survey 2003-2004. J Expo Sci
Environ Epidemiol 2009;19:59-68
Reference Values:
0-35 mcg/specimen
Reference values apply to all ages.
Clinical References: 1. Fillol CC, Dor F, Labat L, et al: Urinary arsenic concentrations and
speciation in residents living in an area with naturally contaminated soils. Sci Total Environ 2010 Feb
1;408(5):1190-1194 2. Caldwell K, Jones R, Verdon C, et al: Levels of urinary total and speciated
arsenic in the US population: National Health and Nutrition Examination Survey 2003-2004. J Expo Sci
Environ Epidemiol 2009 Jan;19(1):59-68
Useful For: Detection of acute or very recent arsenic exposure Monitoring the effectiveness of
therapy
Interpretation: Abnormal blood arsenic concentrations (>12 ng/mL) indicate significant exposure.
Absorbed arsenic is rapidly distributed into tissue storage sites with a blood half-life of <6 hours. Unless
a blood specimen is drawn within 2 days of exposure, arsenic is not likely to be detected in a blood
specimen.
Reference Values:
0-12 ng/mL
Reference values apply to all ages.
Clinical References: Hall M, Chen Y, Ahsan H, et al: Blood arsenic as a biomarker of arsenic
exposure: results from a prospective study. Toxicology 2006;225:225233
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protein in hair and nails, contains many cysteine residues and, therefore, is 1 of the major sites for
accumulation of arsenic. Since arsenic has a high affinity for keratin, the concentration of arsenic in hair
is higher than in other tissues. Arsenic binds to keratin at the time of exposure, "trapping" the arsenic in
hair. Therefore, hair analysis for arsenic is not only used to document that an exposure occurred, but
when it occurred. Hair collected from the nape of the neck can be used to document recent exposure.
Axillary or pubic hair are used to document long-term (6 months-1 year) exposure.
Reference Values:
0-15 years: not established
> or =16 years: 0.0-0.9 mcg/g of hair
Clinical References: 1. Sthiannopkao S, Kim K-W, Cho KH, et al: Arsenic levels in human hair,
Kandal Province, Cambodia: The influences of groundwater arsenic, consumption period, age and gender.
Applied Geochemistry 2010;25:8190 2. Pearse DC, Dowling K, Gerson, AR, et. al: Arsenic
microdistribution and speciation in toenail clippings of children living in a historic gold mining area.
Science of the Total Environment 2010;408:25902599
Reference Values:
0-15 years: not established
> or =16 years: 0.0-0.9 mcg/g of nails
Clinical References: Hindmarsh JT, McCurdy RF: Clinical and environmental aspects of arsenic
toxicity. Crit Rev Clin Lab Sci 1986;23:315-347
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different mechanisms, 2 of them related to energy transfer. Arsenic covalently and avidly binds to
dihydrolipoic acid, a necessary cofactor for pyruvate dehydrogenase. Absence of the cofactor inhibits the
conversion of pyruvate to acetyl coenzyme A, the first step in gluconeogenesis. This results in loss of
energy supply to anaerobic cells, the predominant mechanism of action of arsenic on neural cells that rely
on anaerobic respiration for energy. Neuron cell destruction that occurs after long-term energy loss results
in bilateral peripheral neuropathy. Arsenic also competes with phosphate for binding to adenosine
triphosphate during its synthesis by mitochondria via oxidative phosphorylation, causing formation of the
lower energy adenosine diphosphate monoarsine. This results in loss of energy supply to aerobic cells.
Cardiac cells are particularly sensitive to this form of energy loss; fatigue due to poor cardiac output is a
common symptom of arsenic exposure. Arsenic furthermore binds avidly with any hydrated sulfhydryl
group on protein, distorting the 3-dimensional configuration of that protein, causing it to lose activity.
Interaction of arsenic with epithelial cell protein at the sites of highest physiologic concentration, the
small intestine and proximal tubule of the kidney, results in cellular degeneration. Epithelial cell erosion
in the gastrointestinal tract and proximal tubule are characteristic of arsenic toxicity. Arsenic is also a
known carcinogen, but the mechanism of this effect is not definitively known. A wide range of signs and
symptoms may be seen in acute arsenic poisoning including headache, nausea, vomiting, diarrhea,
abdominal pain, hypotension, fever, hemolysis, seizures, and mental status changes. Symptoms of chronic
poisoning, also called arseniasis, are mostly insidious and nonspecific. The gastrointestinal tract, skin, and
central nervous system are usually involved. Nausea, epigastric pain, colic abdominal pain, diarrhea, and
paresthesias of the hands and feet can occur. Arsenic exists in a number of different forms; organic forms
are nontoxic, inorganic forms are toxic. See ASFRU / Arsenic Fractionation, Random, Urine for details
about arsenic forms. Because arsenic is excreted predominantly by glomerular filtration, analysis for
arsenic in urine is the best screening test to detect arsenic exposure.
Reference Values:
0-35 mcg/L
Reference values apply to all ages.
Clinical References: 1. Fillol CC, Dor F, Labat L, et al: Urinary arsenic concentrations and
speciation in residents living in an area with naturally contaminated soils. Sci Total Environ 2010 Feb
1;408(5):1190-1194 2. Caldwell K, Jones R, Verdon C, et al: Levels of urinary total and speciated
arsenic in the US population: National Health and Nutrition Examination Survey 2003-2004. J Expo Sci
Environ Epidemiol 2009 Jan;19(1):59-68
Reference Values:
0-35 mcg/g Creatinine
Reference values apply to all ages.
Clinical References: 1. Fillol CC, Dor F, Labat L, et al: Urinary arsenic concentrations and
speciation in residents living in an area with naturally contaminated soils. Sci Total Environ 2010 Feb
1;408(5):1190-1194 2. Caldwell K, Jones R, Verdon C, et al: Levels of urinary total and speciated arsenic
in the US population: National Health and Nutrition Examination Survey 2003-2004. J Expo Sci Environ
Epidemiol 2009 Jan;19(1):59-68
Reference Values:
<0.35
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the kidney, gallbladder, and other visceral organs and are excreted in excessive amounts in the urine. The
3 clinical forms of MLD are late-infantile, juvenile, and adult, depending on age of onset. All result in
progressive neurologic changes and leukodystrophy demonstrated on magnetic resonance imaging.
Late-infantile MLD is the most common (50%-60% of cases) and usually presents between age 1 to 2
years with hypotonia, clumsiness, diminished reflexes, and slurred speech. Progressive neurodegeneration
occurs and most patients die within 5 years of the diagnosis. Juvenile MLD (20%-30% of cases) is
characterized by onset between 4 to 14 years. Presenting features are behavior problems, declining school
performance, clumsiness, and slurred speech. Neurodegeneration occurs at a somewhat slower and more
variable rate than the late-infantile form. Adult MLD (15%-20% of cases) has an onset after puberty and
can be as late as the fourth or fifth decade. Presenting features are often behavior and personality changes,
including psychiatric symptoms. Clumsiness, neurologic symptoms, and seizures are also common. The
disease course has variable progression and may occur over 2 to 3 decades. The disease prevalence is
estimated to be approximately 1 in 100,000. MLD is an autosomal recessive disorder and is caused by
mutations in the ARSA gene coding for the ARSA enzyme. This disorder is distinct from conditions
caused by deficiencies of arylsulfatase B (Maroteaux-Lamy disease) and arylsulfatase C (steroid sulfatase
deficiency). Saposin B deficiency is a rare autosomal recessive disorder with symptoms that mimic MLD;
however ARSA enzyme level is normal. Like MLD, patients with saposin B deficiency can also excrete
excessive amounts of sulfatides in their urine. Extremely low ARSA levels have been found in some
clinically normal parents and other relatives of MLD patients. These individuals do not have
metachromatic deposits in peripheral nerve tissues, and their urine content of sulfatide is normal.
Individuals with this "pseudodeficiency" have been recognized with increasing frequency among patients
with other apparently unrelated neurologic conditions as well as among the general population. This has
been associated with a fairly common polymorphism in the ARSA gene which leads to low expression of
the enzyme (5%-20% of normal). These patients can be difficult to differentiate from actual MLD
patients. Additional studies, such as molecular genetic testing of ARSA (ARSAZ / ARSA Gene, Full
Gene Analysis), urinary excretion of sulfatides (CTSA / Ceramide Trihexosides and Sulfatides, Urine),
and/or histological analysis for metachromatic lipid deposits in nervous system tissue are recommended to
confirm a diagnosis. Current treatment options for MLD are focused on managing disease manifestations
such as seizures. Bone marrow transplantation remains controversial, and the effectiveness of enzyme
replacement therapy may be limited due to difficulties crossing the blood-brain barrier. Other treatments
under ongoing investigation include hematopoietic stem cell transplantation and fetal umbilical cord
blood transplantation.
Reference Values:
> or =19 nmol/h/mL
Note: Results from this assay may not reflect carrier status because of individual variation of
arylsulfatase A enzyme levels.
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ARST Arylsulfatase A, Fibroblasts
8778 Clinical Information: Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused
by a deficiency of the arylsulfatase A enzyme, which leads to the accumulation of galactosyl sulfatide
(cerebroside sulfate) in the white matter of the central nervous system and in the peripheral nervous
system. Deficiency of the arylsulfatase A enzyme leads to the accumulation of sulfatides (both galactosyl
and lactosyl sulfatide) in the white matter of the central nervous system, the peripheral nervous system,
and visceral organs including the kidney and gallbladder. Patients with MLD excrete excessive amounts
of sulfatides in their urine. The 3 clinical forms of MLD are late-infantile, juvenile, and adult, which are
categorized based on age of onset. All forms result in progressive neurologic changes and leukodystrophy
demonstrated on magnetic resonance imaging. Late-infantile MLD is the most common (50%-60% of
cases) and typically presents between 6 months to 2 years of age with hypotonia, clumsiness, diminished
reflexes, and slurred speech. Progressive neurodegeneration occurs with most patients dying within 5
years of the diagnosis. Juvenile MLD (20%-30% of cases) is characterized by onset between 4 to 14
years. Typical presenting features are behavior problems, declining school performance, clumsiness, and
slurred speech. Neurodegeneration occurs at a somewhat slower and more variable rate than the
late-infantile form. Adult MLD (15%-20% of cases) has an onset after puberty and can be as late as the
fourth or fifth decade. Presenting features are often behavior and personality changes, including
psychiatric symptoms. Clumsiness, neurologic symptoms, and seizures are also common. The disease
course has variable progression and may occur over 2 to 3 decades. The disease prevalence is estimated to
be approximately 1 in 100,000. MLD is an autosomal recessive disorder and is caused by mutations in the
ARSA gene coding for the arylsulfatase A enzyme. This disorder is distinct from conditions caused by
deficiencies of arylsulfatase B (Maroteaux-Lamy disease) and arylsulfatase C (steroid sulfatase
deficiency). Saposin B deficiency can have an identical clinical presentation to MLD but arylsulfatase A
enzyme level is normal; however, patients with saposin B deficiency also excrete excessive amounts of
sulfatides in their urine. Extremely low arylsulfatase A levels have been found in some clinically normal
parents and other relatives of MLD patients. These individuals do not have metachromatic deposits in
peripheral nerve tissues, and their urine content of sulfatide is normal. Individuals with this
"pseudodeficiency" have been recognized with increasing frequency among patients with other apparently
unrelated neurologic conditions as well as among the general population. This has been associated with
fairly common polymorphisms in the ARSA gene, which leads to low expression of the enzyme (5%-20%
of normal). These patients can be difficult to differentiate from actual MLD patients. Additional studies,
such as molecular genetic testing of ARSA (ARSAZ / ARSA Gene, Full Gene Analysis), urinary
excretion of sulfatides (CTSA / Ceramide Trihexosides and Sulfatides, Urine), and/or histological analysis
for metachromatic lipid deposits in nervous system tissue are recommended to confirm a diagnosis.
Current treatment options for MLD are focused on managing disease manifestations such as seizures.
Bone marrow transplantation remains controversial, and the effectiveness of enzyme replacement therapy
may be limited due to difficulties crossing the blood-brain barrier. Other treatments under ongoing
investigation include hematopoietic stem cell transplantation and fetal umbilical cord blood
transplantation.
Reference Values:
> or =4.25 nmol/min/mg protein
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ARSAW Arylsulfatase A, Leukocytes
8779 Clinical Information: Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder
caused by a deficiency of the arylsulfatase A (ARSA) enzyme, which leads to the accumulation of
sulfatides (both galactosyl and lactosyl sulfatide) in the white matter of the central nervous system, the
peripheral nervous system, and to a lesser extent, in visceral organs including the kidney and
gallbladder. Patients with MLD excrete excessive amounts of sulfatides in their urine. The 3 clinical
forms of MLD are late-infantile, juvenile, and adult, which are categorized based on age of onset. All
forms result in progressive neurologic changes and leukodystrophy demonstrated on magnetic
resonance imaging. Late-infantile MLD is the most common (50%-60% of cases) and usually presents
between 6 months to 2 years of age with hypotonia, clumsiness, diminished reflexes, and slurred
speech. Progressive neurodegeneration occurs with most patients dying within 5 years of the diagnosis.
Juvenile MLD (20%-30% of cases) is characterized by onset between 4 to 14 years. Presenting features
are behavior problems, declining school performance, clumsiness, and slurred speech.
Neurodegeneration occurs at a somewhat slower and more variable rate than the late-infantile form.
Adult MLD (15%-20% of cases) has an onset after puberty and can be as late as the fourth or fifth
decade. Presenting features are often behavior and personality changes, including psychiatric symptoms.
Clumsiness, neurologic symptoms, and seizures are also common. The disease course has variable
progression and may occur over 2 to 3 decades. The disease prevalence is estimated to be approximately
1 in 100,000. MLD is an autosomal recessive disorder and is caused by mutations in the ARSA gene
coding for the ARSA enzyme. This disorder is distinct from conditions caused by deficiencies of
arylsulfatase B (Maroteaux-Lamy disease) and arylsulfatase C (steroid sulfatase deficiency). Saposin B
deficiency is a rare autosomal recessive disorder with symptoms that mimic MLD; however ARSA
enzyme level is normal. Like MLD, patients with saposin B deficiency can also excrete excessive
amounts of sulfatides in their urine. Extremely low ARSA levels have been found in some clinically
normal parents and other relatives of MLD patients. These individuals do not have metachromatic
deposits in peripheral nerve tissues, and their urine content of sulfatide is normal. Individuals with this
"pseudodeficiency" have been recognized with increasing frequency among patients with other
apparently unrelated neurologic conditions as well as among the general population. This has been
associated with fairly common polymorphisms in the ARSA gene, which leads to low expression of the
enzyme (5%-20% of normal). These patients can be difficult to differentiate from actual MLD patients.
Additional studies, such as molecular genetic testing of ARSA (ARSAZ / ARSA Gene, Full Gene
Analysis), urinary excretion of sulfatides (CTSA / Ceramide Trihexosides and Sulfatides, Urine), and/or
histological analysis for metachromatic lipid deposits in nervous system tissue are recommended to
confirm a diagnosis. Current treatment options for MLD are focused on managing disease
manifestations such as seizures. Bone marrow transplantation remains controversial, and the
effectiveness of enzyme replacement therapy may be limited due to difficulties crossing the blood-brain
barrier. Other treatments under ongoing investigation include hematopoietic stem cell transplantation
and fetal umbilical cord blood transplantation.
Reference Values:
> or =62 nmol/h/mg
Note: Results from this assay may not reflect carrier status because of individual variation of
arylsulfatase A enzyme levels. Low normal values may be due to the presence of pseudodeficiency gene
or carrier gene. Patients with these depressed levels may be phenotypically normal.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 205
Accessed 01/21/2015 2. Fluharty AL: Arylsulfatase A deficiency. Available at
www.ncbi.nlm.nih.gov/books/NBK1130. Accessed 1/21/2015 3. Mahmood A, Berry J, Wenger D, et al:
Metachromatic leukodystrophy: a case of triplets with the late infantile variant and a systematic review
of the literature. J Child Neurol 2010;25(5):572-580 4. van Rappard DF, Boelens JJ, Wolf NI:
Metachromatic leukodystrophy: Disease spectrum and approaches for treatment. Best Pract Res Clin
Endocrinol Metab 2015 Mar;29(2):261-273. DOI: 10.1016/j.beem.2014.10.001
Reference Values:
> or =6.08 nmol/min/mg protein
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ASCRI Ascaris, IgE
82764 Clinical Information: Clinical manifestations of immediate hypersensitivity (allergic) diseases are
caused by the release of proinflammatory mediators (histamine, leukotrienes, and prostaglandins) from
immunoglobulin E (IgE)-sensitized effector cells (mast cells and basophils) when cell-bound IgE
antibodies interact with allergen. In vitro serum testing for IgE antibodies provides an indication of the
immune response to allergens that may be associated with allergic disease. The allergens chosen for
testing often depend upon the age of the patient, history of allergen exposure, season of the year, and
clinical manifestations. In individuals predisposed to develop allergic disease, the sequence of
sensitization and clinical manifestations proceed as follows: eczema and respiratory disease (rhinitis and
bronchospasm) in infants and children less than 5 years due to food sensitivity (milk, egg, soy, and
wheat proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 207
addition, vitamin C appears to function in a variety of other metabolic processes in which its role has
not been well characterized. Prolonged deficiency of vitamin C leads to the development of scurvy, a
disease characterized by an inability to form adequate intercellular substance in connective tissues. This
results in the formation of swollen, ulcerative lesions in the gums, mouth, and other tissues that are
structurally weakened. Early symptoms may include weakness, easy fatigue and listlessness, as well as
shortness of breath, and aching joints, bones, and muscles. The need for vitamin C can be increased by
the use of aspirin, oral contraceptives, tetracycline, and a variety of other medications. Psychological
stress and advancing age also tend to increase the need for vitamin C. Among the elderly, lack of fresh
fruit and vegetables often adds vitamin C depletion to the inherently increased need, with development
of near-scurvy status
Reference Values:
0.4-2.0 mg/dL
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manifestations of this condition include progressive neurodegeneration, seizures, and blindness, leading to
total incapacitation and death. This panel tests for the 3 common mutations in the Ashkenazi Jewish
population: 1278insTATC, G269S, and IVS12+1G->C. Also included in this assay are the mutations
IVS9+1G->A and delta7.6kb mutations along with the R247W and R249W polymorphisms associated
with pseudodeficiency. Familial Dysautonomia: Familial dysautonomia affects sensory, parasympathetic,
and sympathetic neurons. Patients experience gastrointestinal dysfunction, pneumonia, vomiting episodes,
altered sensitivity to pain and temperature, and cardiovascular problems. Progressive neuronal
degeneration continues throughout the lifespan. Mutations in the IKBKAP gene cause the clinical
manifestations of familial dysautonomia. Two mutations in the IKBKAP gene are common in the
Ashkenazi Jewish population: IVS20(+6)T->C and R696P. Canavan Disease: Canavan disease is a severe
leukodystrophy resulting from a deficiency of the enzyme aspartoacylase. Mutations in the ASPA gene
cause the clinical manifestations of Canavan disease. The deficiency of aspartoacylase leads to spongy
degeneration of the brain, and the disease is characterized by delayed development beginning at age 3 to 6
months, head lag, macrocephaly, and hypotonia. Death usually occurs in the first decade of life. Four
ASPA mutations are included in this test: 433(-2)A->G, A305E, E285A, and Y231X. Mucolipidosis IV:
Mucolipidosis IV is a lysosomal storage disease characterized by mental retardation, hypotonia, corneal
clouding, and retinal degeneration. Mutations in the MCOLN1 gene are responsible for the clinical
manifestations of mucolipidosis IV. Two mutations in the MCOLN1 gene account for the majority of
mutations in the Ashkenazi Jewish population: IVS3(-2)A->G and delta6.4kb. Niemann-Pick Disease
Types A and B: Niemann-Pick disease (types A and B) is a lysosomal storage disease caused by a
deficiency of the enzyme acid sphingomyelinase. The clinical presentation of type A disease is
characterized by jaundice, progressive loss of motor skills, feeding difficulties, learning disabilities, and
hepatosplenomegaly. Death usually occurs by age 3. Type B disease is milder, though variable in its
clinical presentation. Most individuals with type B do not have neurologic involvement and survive to
adulthood. Mutations in the SMPD1 gene are known to cause Niemann-Pick disease types A and B. There
are 3 common mutations causing Niemann-Pick type A in the Ashkenazi Jewish population: L302P,
R496L, and fsP330. The deltaR608 mutation accounts for approximately 90% of the type B mutant alleles
in individuals from the Maghreb region of North Africa and 100% of the mutation alleles in Gran Canaria
Island. Fanconi Anemia: Fanconi anemia is an aplastic anemia that leads to bone marrow failure and
myelodysplasia or acute myelogenous leukemia. Physical findings include short stature; upper limb, lower
limb, and skeletal malformations; and abnormalities of the eyes and genitourinary tract. Mutations in
several genes have been associated with Fanconi anemia, although 1 mutation, IVS4(+4)A->T, in the
FANCC gene is common in the Ashkenazi Jewish population. A second mutation, 322delG, is over
represented in FANCC patients of Northern European ancestry. Bloom Syndrome: Bloom syndrome is
characterized by short stature, sun sensitivity, susceptibility to infections, and a predisposition to cancer.
Mutations in the BLM gene lead to genetic instability (increased chromosomal breakage and sister
chromatid exchange) and cause the clinical manifestations of Bloom syndrome. The protein encoded by
the BLM gene is a helicase involved in maintaining DNA integrity. There is a common mutation in the
Ashkenazi Jewish population: 2281delATCTGAinsTAGATTC (2281del6/ins7). Because of the high
sensitivity of carrier testing in the Ashkenazi Jewish population, the American College of Medical
Genetics and Genomics (ACMG) recommends that carrier screening for cystic fibrosis (CF), Canavan,
Tay-Sachs, familial dysautonomia, Niemann-Pick type A, Fanconi anemia (FANCC), Bloom syndrome,
mucolipidosis IV, and Gaucher disease be offered to individuals of Ashkenazi Jewish ancestry. The
mutation detection rates and carrier frequencies for the diseases included in this panel are listed below. Of
note, testing for CF is not included in this panel. If testing for this disorder is desired, please see details
and ordering information under CFP / Cystic Fibrosis Mutation Analysis, 106-Mutation Panel. Disease
Carrier Rate in the AJ Population Mutation Detection Rate Gaucher 1/18 95% Tay-Sachs 1/31 *99%
Familial dysautonomia 1/31 99% Canavan 1/41 98% Mucolipidosis IV 1/127 95% Niemann-Pick type
A/B 1/90 97% FANCC-related Fanconi anemia 1/89 >99% Bloom syndrome 1/107 >99% *with
biochemical testing The Ashkenazi Jewish panel is useful for identifying carriers of these 8 conditions in
an at-risk population. Because the diseases included in the panel are inherited in an autosomal recessive
manner, the presence of a family history is not a prerequisite for testing consideration. The identification
of disease-causing mutations allows for carrier testing of at-risk family members and prenatal diagnosis
for pregnancies in which both parents are known carriers. Refer to Carrier Testing for Tay-Sachs Disease
and Other GM2 Gangliosidosis Variants: Supplementing Traditional Biochemical Testing with Molecular
Methods, Mayo Medical Laboratories Communique 2004 Jul;29(7) for more information regarding
diagnostic strategy. Of note, approximately 1 in 25 individuals of Ashkenazi Jewish ancestry are also
carriers of cystic fibrosis (CF). Therefore, the American College of Medical Genetics also recommends
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that carrier screening for CF be offered to individuals of Ashkenazi Jewish ancestry who are pregnant or
considering pregnancy. Carrier screening for CF is available by ordering CFP / Cystic Fibrosis Mutation
Analysis, 106-Mutation Panel.
Useful For: Carrier screening in individuals of Ashkenazi Jewish ancestry for Bloom syndrome,
Canavan disease, FANCC-related Fanconi anemia, familial dysautonomia, Gaucher disease,
mucolipidosis IV, Niemann-Pick disease types A and B, and Tay-Sachs disease
Clinical References: Gross SJ, Pletcher BA, Monaghan KG: Carrier screening individuals of
Ashkenazi Jewish descent. Genet Med 2008:10(1):54-56
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 210
Company, New York, 2007, Part VI, pp 961-971
Useful For: Diagnosing and monitoring liver disease, particularly diseases resulting in a destruction
of hepatocytes
Interpretation: Elevated aspartate aminotransferase (AST) values are seen in parenchymal liver
diseases characterized by a destruction of hepatocytes. Values are typically at least 10 times above the
normal range. Levels may reach values as high as one hundred times the upper reference limit, although
twenty to fifty-fold elevations are most frequently encountered. In infectious hepatitis and other
inflammatory conditions affecting the liver, alanine aminotransferase (ALT) is characteristically as high
as or higher than AST, and the ALT/AST ratio, which normally and in other condition is less than 1,
becomes greater than unity. AST levels are usually elevated before clinical signs and symptoms of
disease appear. Five- to 10-fold elevations of both AST and ALT occur in patients with primary or
metastatic carcinoma of the liver, with AST usually being higher than ALT, but levels are often normal
in the early stages of malignant infiltration of the liver. Elevations of ALT activity persist longer than do
those of AST activity. Elevated AST values may also be seen in disorders affecting the heart, skeletal
muscle and kidney.
Reference Values:
Males
0-11 months: not established
1-13 years: 8-60 U/L
> or =14 years: 8-48 U/L
Females
0-11 months: not established
1-13 years: 8-50 U/L
> or =14 years: 8-43 U/L
Reference Values:
<0.35 kU/L
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80% due in part to the rapid progression of the infection (ie, 1-2 weeks from onset to death).
Approximately 30% of cases remain undiagnosed and untreated at death. Definitive diagnosis of IA
requires histopathological evidence of deep-tissue invasion or a positive culture. However, this evidence
is often difficult to obtain due to the critically ill nature of the patient and the fact that severe
thrombocytopenia often precludes the use of invasive procedures to obtain a quality specimen. The
sensitivity of culture in this setting also is low, reportedly ranging from 30% to 60% for
bronchoalveolar lavage fluid. Accordingly, the diagnosis is often based on nonspecific clinical
symptoms (unexplained fever, cough, chest pain, dyspnea) in conjunction with radiologic evidence
(computed tomography [CT] scan); and definitive diagnosis is often not established before fungal
proliferation becomes overwhelming and refractory to therapy. Recently, a serologic assay was
approved by the Food and Drug Administration for the detection of galactomannan, a molecule found in
the cell wall of Aspergillus species. Serum galactomannan can often be detected a mean of 7 to 14 days
before other diagnostic clues become apparent, and monitoring of galactomannan can potentially allow
initiation of preemptive antifungal therapy before life-threatening infection occurs.
Useful For: An aid in the diagnosis of invasive aspergillosis and assessing response to therapy
Interpretation: A positive result supports a diagnosis of invasive aspergillosis (IA). Positive results
should be considered in conjunction with other diagnostic procedures, such as microbiologic culture,
histological examination of biopsy specimens, and radiographic evidence. See Cautions. A negative result
does not rule out the diagnosis of IA. Repeat testing is recommended if the result is negative but IA is
suspected. Patients at risk of IA should have a baseline serum tested and should be monitored twice a
week for increasing galactomannan antigen levels. Galactomannan antigen levels may be useful in the
assessment of therapeutic response. Antigen levels decline in response to antimicrobial therapy.
Reference Values:
<0.5 index
Interpretive Criteria:
Negative: Antibody not detected
Positive: Antibody detected
A positive result is represented by 1 or more precipitin bands, and may indicate fungus ball, allergic
bronchopulmonary aspergillosis (ABA) or invasive aspergillosis. Generally, the appearance of 3 4
bands indicates either fungus ball or ABA.
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ASPBA Aspergillus Antigen, Bronchoalveolar Lavage
61009 Clinical Information: Invasive aspergillosis (IA) is a severe infection that occurs in patients with
prolonged neutropenia following transplantation or in conjunction with aggressive immunosuppressive
regimens (eg, prolonged corticosteroid use, chemotherapy). The incidence of IA is reported to vary
from 5% to 20% depending on the patient population. IA has an extremely high mortality rate of 50% to
80%, due in part to the rapid progression of the infection (ie, 1-2 weeks from onset to death).
Approximately 30% of cases remain undiagnosed and untreated at death. Definitive diagnosis of IA
requires histopathological evidence of deep-tissue invasion or a positive culture. However, this evidence
is often difficult to obtain due to the critically ill nature of the patient and the fact that severe
thrombocytopenia often precludes the use of invasive procedures to obtain a quality specimen. The
sensitivity of culture in this setting also is low, reportedly ranging from 30% to 60% for
bronchoalveolar lavage (BAL) fluid. Accordingly, the diagnosis is often based on nonspecific clinical
symptoms (unexplained fever, cough, chest pain, dyspnea) in conjunction with radiologic evidence
(computed tomography scan), and a definitive diagnosis is often not established before fungal
proliferation becomes overwhelming and refractory to therapy. Recently, a serologic assay was
approved by the FDA for the detection of galactomannan, a molecule found in the cell wall of
Aspergillus species. Serum galactomannan (Aspergillus antigen) can often be detected a mean of 7 to 14
days before other diagnostic clues become apparent, and monitoring of Aspergillus antigen can
potentially allow initiation of preemptive antifungal therapy before life-threatening infection occurs.
The clinical utility of Aspergillus antigen testing in BAL specimens as an early prognostic indicator of
IA has recently been assessed. These studies demonstrated equivalent or higher sensitivity compared to
detection of Aspergillus antigen in serum.(1-4) This assay may be useful in the assessment of
therapeutic response as antigen levels typically decline in response to effective antimicrobial therapy.
Useful For: Aids in the diagnosis of invasive aspergillosis and assessing response to therapy
Interpretation: A positive result in bronchoalveolar lavage (BAL) fluid supports a diagnosis of
invasive, pulmonary aspergillosis. Positive results should be considered in conjunction with other
diagnostic procedures, such as microbiologic culture, histological examination of biopsy specimens, and
radiographic evidence (see Cautions). A negative result in BAL fluid does not rule out the diagnosis of
invasive aspergillosis (IA). Patients at risk of IA should be monitored twice a week for Aspergillus
antigen levels in serum until determined to be clinically unnecessary. Aspergillus antigen levels
typically decline in response to effective antimicrobial therapy.
Reference Values:
<0.5 Index
Clinical References: 1. Park SY, Lee S, Choi S, et al: Aspergillus galactomannan antigen assay in
bronchoalveolar lavage fluid for diagnosis of invasive pulmonary aspergillosis. J Infect
2010;61:492-498 2. Husain S, Clancy CJ, Nguyen MH, et al: Performance characteristics of the Platelia
aspergillus enzyme immunoassay for detection of Aspergillus galactomannan antigen in
bronchoalveolar lavage fluid. Clin Vaccine Immunol 2008;15(12):1760-1763 3. Meersseman W,
Lagrou K, Maertens J, et al: Galactomannan in bronchoalveolar lavage fluid a tool for diagnosing
aspergillosis in intensive care unit patients. Am J Respir Crit Care Med 2008;177:27-34 4. Becker MJ,
Lugtenburg EJ, Cornelissen JJ, et al: Galactomannan detection in computerized tomography-based
bronchoalveolar lavage fluid and serum in haematological patients at risk for invasive pulmonary
aspergillosis. Br J haematol 2003;121:448-457 5. Xavier MO, Pasqualotto AC, Cardoso IC,Severo LC.
Cross-reactivity of Paracoccidioides brasiliensis, Histoplasma capsulatum, and Cryptococcus species in
the commercial Platelia Aspergillus enzyme immunoassay. Clin Vaccine Immunol 2009
Jan;16(1):132-133
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Reference Values:
<0.35 kU/L
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
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bronchopulmonary disease is not known, several immune mechanisms are postulated to play a role,
including both cellular and humoral mechanisms.
Useful For: Evaluation of patients suspected of having lung disease caused by Aspergillus fumigatus
Interpretation: Elevated concentrations of IgG antibodies to Aspergillus fumigatus,
Thermoactinomyces vulgaris, or Micropolyspora faeni in patients with signs and symptoms of
hypersensitivity pneumonitis may be consistent with disease caused by exposure to 1 or more of these
organic antigens.
Reference Values:
<4 years: not established
> or =4 years: < or =102 mg/L
Clinical References: 1. Fink JN, Zacharisen MC: Chapter 69: Hypersensitivity pneumonitis. In
Allergy Principles and Practice. Vol 1. Fifth edition. Edited by E Middleton Jr, CE Reed, EF Ellis, et al.
St. Louis, Mosby Year Book Inc, 1998 2. Girard M, Lacasse Y, Cormier Y: Hypersensitivity
pneumonitis. Allergy 2009;64:322-334 3. Grunes D, Beasley MB: Hypersensitivity pneumonitis: A
review and update of histologic findings. J Clin Pathol 2013;66:888-895
Reference Values:
Negative
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 215
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: An adjunct to other risk markers for assessing an individual's likelihood of future coronary
events, in patients with coronary heart disease, type-II diabetes mellitus, or kidney disease
Interpretation: In patients with pre-existing coronary conditions or at high risk for coronary events
(diabetes, renal insufficiency), asymmetric dimethylarginine (ADMA) levels in the upper tertile, >112
ng/mL, confer an increased risk for future coronary events. Reductions in ADMA are not known to be
predictive of decreased risk of future coronary effects.
Reference Values:
<18 years: not established
> or =18 years: 63-137 ng/mL
Order MPCT / Muscle Pathology Consultation. The consultant will determine the need for special
stains.
Clinical References: 1. Wiestler B, Capper D, Holland-Letz T, et al: ATRX loss refines the
classification of anaplastic gliomas and identifies a subgroup of IDH mutant astrocytic tumors with
better prognosis. Acta Neuropathol 2013 Sep;126(3):443-451 2. De La Fuente R, Baumann C, Viveiros
MM, et al: Role of ATRX in chromatin structure and function: implications for chromosome instability
and human disease. Reproduction 2011 Aug;142(2):221-234 3. Zhang J, Francois R, Iyer R, et al:
Current understanding of the molecular biology of pancreatic neuroendocrine tumors. J Natl Cancer Inst
2013 Jul 17;105(14):1005-1017
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motives) activity is associated with TTP and is one laboratory feature that distinguishes TTP from HUS.
HUS can also have a number of causes; one of the rarer forms of disease is caused by defects in the
alternative pathway of the complement system, so called atypical-HUS (aHUS). Patients with defective
alternative pathway regulation can benefit from biologics that suppress the complement system. The
purpose of this panel is to aid in the differential diagnosis of TMAs. The suggested approach is to
rule-out other causes of TMAs first, since aHUS is one of the rarer causes of TMAs. Additionally, the
assays can be used in the setting of membranoproliferative glomerulonephritis (MPGN), and help
distinguish between immune-complex mediated or complement-mediated kidney disease. MPGN
mediated by immune-complexes are the ones resulting from infectious processes, autoimmune diseases,
or monoclonal gammopathies, whereas complement-mediated MPGN can then be subdivided in C3
glomerulonephritis (C3GN) and dense deposit disease (DDD), based on electron microscopy of the
kidney biopsy histological findings. Despite phenotypic differences, these glomerular diseases share
dysfunction of the alternative pathway as the defining pathophysiology.
Useful For: Detecting deficiencies in the alternative pathway that can cause atypical-hemolytic uremic
syndrome, dense deposit disease, and C3 glomerulonephritis A second-order test that aids in the
differential diagnosis of thrombotic microangiopathies
SC5b-9 COMPLEMENT
< or =250 ng/mL
COMPLEMENT C4
14-40 mg/dL
COMPLEMENT C3
75-175 mg/dL
COMPLEMENT, TOTAL
> or =16 years: 30-75 U/mL
Reference values have not been established for patients who are <16 years of age.
Clinical References: 1. Daha MR: Role of complement in innate immunity and infections. Crit Rev
Immunol 2010;30(1):47-52 2. Prohaszka Z, Varga L, Fust G: The use of real-time complement
analysis to differentiate atypical haemolytic uraemic syndrome from other forms of thrombotic
microangiopathies. Br J Haematol 2012;158(3):424-425 3. Cataland SR, Holers VM, Geyer S, et al:
Biomarkers of terminal complement activation confirm the diagnosis of aHUS and differentiate aHUS
from TTP. Blood 2014;123(24):3733-3738
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 219
sensitization and clinical manifestations proceed as follows: eczema and respiratory disease (rhinitis and
bronchospasm) in infants and children less than 5 years due to food sensitivity (milk, egg, soy, and
wheat proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 220
social/environmental exposure to carcinogens. Early diagnosis and treatment of the neoplasm favors
neurologic improvement and lessens morbidity. Autoantibodies to other onconeural proteins shared by
neurons, glia or muscle (eg, antineuronal nuclear antibody-type 1: ANNA-1, CRMP-5-IgG, N-type
voltage-gated calcium channel, muscle AChR and sarcomeric [striational antigens]) serve as additional
markers of paraneoplastic or idiopathic dysautonomia. A specific neoplasm is often predictable by the
individual patient's autoantibody profile.
Useful For: Investigating idiopathic dysautonomic symptoms Directing a focused search for cancer
in patients with idiopathic dysautonomia Investigating autonomic symptoms that appear in the course or
wake of cancer therapy, and are not explainable by recurrent cancer or metastasis (detection of
autoantibodies in this profile helps differentiate autoimmune dysautonomia from the effects of
chemotherapy)
Interpretation: Antibodies directed at onconeural proteins shared by neurons, muscle, and glia are
valuable serological markers of a patient's immune response to cancer. These autoantibodies are not
found in healthy subjects, and are usually accompanied by subacute neurological symptoms and signs. It
is not uncommon for more than 1 autoantibody to be detected in patients with autoimmune
dysautonomia. These include: -Plasma membrane cation channel antibodies (neuronal ganglionic
[alpha-3] and muscle [alpha-1] acetylcholine receptor; neuronal calcium channel N-type or P/Q-type,
and neuronal voltage-gated potassium channel antibodies). All of these autoantibodies are potential
effectors of autonomic dysfunction. -Antineuronal nuclear autoantibody-type 1 -Neuronal and muscle
cytoplasmic antibodies (CRMP-5 IgG, glutamic acid decarboxylase and striational) A rising
autoantibody titer in previously seropositive patients suggests cancer recurrence.
Reference Values:
CATION CHANNEL ANTIBODIES
N-Type Calcium Channel Antibody
< or =0.03 nmol/L
P/Q-Type Calcium Channel Antibody
< or =0.02 nmol/L
AChR Ganglionic Neuronal Antibody
< or =0.02 nmol/L
Neuronal VGKC Autoantibody
< or =0.02 nmol/L
Glutamic Acid Decarboxylase (GAD65) Antibody
< or =0.02 nmol/L
Clinical References: 1. Vernino S, Low PA, Fealey RD, et al: Autoantibodies to ganglionic
acetylcholine receptors in autoimmune autonomic neuropathies. N Engl J Med 2000;343:847-855 2.
O'Suilleabhain P, Low PA, Lennon VA: Autonomic dysfunction in the Lambert-Eaton myasthenic
syndrome: serologic and clinical correlates. Neurology 1998;50:88-93 3. Dhamija R, Tan KM, Pittock SJ,
et al: Serological profiles aiding the diagnosis of autoimmune gastrointestinal dysmotility. Clin
Gastroenterol Hepatol 2008;6:988-992 4. McKeon A, Lennon VA, Lachance DH, et al: The ganglionic
acetylcholine receptor autoantibody: oncological, neurological and serological accompaniments. Arch
Neurol 66(6):735-741
Useful For: Investigating unexplained weight loss, early satiety, anorexia, nausea, vomiting,
constipation or diarrhea in a patient with past or family history of cancer or autoimmunity Directing a
focused search for cancer Investigating gastrointestinal symptoms that appear in the course or wake of
cancer therapy, not explainable by recurrent cancer, metastasis or therapy; detection of autoantibodies
on this profile helps differentiate autoimmune gastrointestinal dysmotility from the effects of
chemotherapy Detecting early evidence of cancer recurrence in previously seropositive patients who
have a rising titer of 1 or more autoantibodies
Interpretation: Antibodies directed at onconeural proteins shared by neurons, muscle, and certain
cancers are valuable serological markers of a patient's immune response to cancer. They are not found
in healthy subjects, and are usually accompanied by subacute symptoms and signs. It is not uncommon
for more than 1 antibody to be detected. Three classes of antibodies are recognized (the individual
antibodies from each class included in the profile are denoted in parentheses): -Antineuronal nuclear
autoantibody-type 1 -Neuronal and muscle cytoplasmic (CRMP-5, glutamic acid decarboxylase, and
striational) -Plasma membrane cation channel (neuronal ganglionic [alpha-3-AChR (acetylcholine
receptor)] and muscle AChR, neuronal voltage-gated N-type calcium channel, neuronal voltage-gated
potassium channel antibodies). All of these autoantibodies are potential effectors of autoimmune
gastrointestinal dysmotility.
Reference Values:
NEURONAL NUCLEAR ANTIBODIES
Antineuronal Nuclear Ab, Type 1 (ANNA-1)
<1:240
Antineuronal Nuclear Ab, Type 2 (ANNA-2)
<1:240
Antineuronal Nuclear Ab, Type 3 (ANNA-3)
<1:240
Anti-Glial/Neuronal Nuclear Ab, Type 1 (AGNA-1)
<1:240
Clinical References: 1. Lennon VA, Sas DF, Busk MF, et al: Enteric neuronal autoantibodies in
pseudo-obstruction with small cell lung carcinoma. Gastroenterology 1991;100:137-142 2. Lucchinetti
CF, Kimmel DW, Lennon VA: Paraneoplastic and oncological profiles of patients seropositive for type 1
anti-neuronal nuclear autoantibodies. Neurology 1998;50:652-657 3. Vernino S, Adamski J, Kryzer TJ, et
al: Neuronal nicotinic ACh receptor antibody in subacute autonomic neuropathy and cancer-related
syndromes. Neurology 1998;50:1806-1813 4. Vernino S, Low PA, Fealey RD, et al: Autoantibodies to
ganglionic acetylcholine receptors in autoimmune autonomic neuropathies. N Engl J Med
2000;343:847-855 5. Dhamija R, Tan KM, Pittock SJ, et al: Serological profiles aiding the diagnosis of
autoimmune gastrointestinal dysmotility. Clin Gastroenterol Hepatol 2008;6:988-992 6. McKeon A,
Lennon VA, Lachance DH, et al: The ganglionic acetylcholine receptor autoantibody: oncological,
neurological and serological accompaniments. Arch Neurol 2009;66(6):735-741 7. Kraichely RE,
Farrugia G, Castell DO, et al: Neural autoantibody profile of primary achalasia. Dig Dis Sci 2010
Feb;55(2):307-311
Useful For: Evaluation of patients with suspected autoimmune liver disease, specifically
autoimmune hepatitis or primary biliary cirrhosis. Evaluation of patients with liver disease of unknown
etiology.
Interpretation: The presence of smooth muscle antibodies (SMAs) and/or antinuclear antibodies
(ANAs) is consistent with a diagnosis of chronic autoimmune hepatitis, in patients with clinical and/or
laboratory evidence of hepatocellular damage. The presence of anti-mitochondrial antibodies (AMAs) is
consistent with a diagnosis of primary biliary cirrhosis, in patients with clinical and/or laboratory
evidence of hepatobiliary damage.
Reference Values:
SMOOTH MUSCLE ANTIBODIES
Negative
If positive, results are titered.
Reference values apply to all ages
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 225
ARPKZ Autosomal Recessive Polycystic Kidney Disease (ARPKD), Full
35359 Gene Analysis
Clinical Information: Autosomal recessive polycystic kidney disease (ARPKD) is a disorder caused
by mutations in the polycystic kidney and hepatic disease 1 (PKHD1) gene. The incidence of ARPKD is
approximately 1:20,000 and the estimated carrier frequency in the general population is 1:70. ARPKD is
characterized by enlarged echogenic kidneys, congenital hepatic fibrosis, and pulmonary hypoplasia
(secondary to oligohydramnios [insufficient volume of amniotic fluid] in utero). Most individuals with
ARPKD present during the neonatal period and, of those, nearly one-third die of respiratory insufficiency.
Early diagnosis, in addition to initiation of renal replacement therapy (dialysis or transplantation) and
respiratory support, increases the 10-year survival rate significantly. Presenting symptoms include
bilateral palpable flank masses in infants and subsequent observation of typical findings on renal
ultrasound, often within the clinical context of hypertension and prenatal oligohydramnios. In rarer cases,
individuals may present during childhood or adulthood with hepatosplenomegaly. Of those who survive
the neonatal period, one-third progress to end-stage renal disease and up to one-half develop chronic renal
insufficiency. The PKHD1 gene maps to 6p12 and includes 67 exons. The PKHD1 gene encodes a protein
called fibrocystin, which is localized to the primary cilia and basal body of renal tubular and biliary
epithelial cells. Because ARPKD is an autosomal recessive disease, affected individuals must carry 2
deleterious mutations within the PKHD1 gene. Although disease penetrance is 100%, intrafamilial
variation in disease severity has been observed. Mutation detection is often difficult due to the large gene
size and the prevalence of private mutations that span the entire length of the gene.
Useful For: Diagnosis of individuals suspected of having autosomal recessive polycystic kidney
disease (ARPKD) Prenatal diagnosis if there is a high suspicion of ARPKD based on ultrasound findings
Carrier testing of individuals with a family history of ARPKD but an affected individual is not available
for testing or disease-causing mutations have not been identified
Interpretation: All detected alterations are evaluated according to American College of Medical
Genetics recommendations.(1) Variants are classified based on known, predicted, or possible
pathogenicity and reported with interpretive comments detailing their potential or known significance.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for
standards of interpretation and reporting of sequence variations: revisions 2007. Genet Med
2008;10(4):294-300 2. Guay-Woodford LM, Desmond RA: Autosomal recessive polycystic kidney
disease: the clinical experience in North America. Pediatrics 2003;111:1072-1080 3. Gunay-Aygun M,
Avner E, Bacallao RL, et al: Autosomal recessive polycystic kidney disease and congenital hepatic
fibrosis: summary of a first National Institutes of Health/Office of Rare Diseases conference. J Pediatr
2006;149:159-164 4. Harris PC, Rossetti S: Molecular genetics of autosomal recessive polycystic kidney
disease. Mol Genet Metab 2004;81:75-85
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical utility
of food-specific IgG tests has not been established. These tests can be used in special clinical situations to
select foods for evaluation by diet elimination and challenge in patients who have food-related
complaints. It should be recognized that the presence of food-specific IgG alone cannot be taken as
evidence of food allergy and only indicates immunologic sensitization by the food allergen in question.
This test should only be ordered by physicians who recognize the limitations of the test.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 226
AVOC Avocado, IgE
82812 Clinical Information: Clinical manifestations of immediate hypersensitivity (allergic) diseases are
caused by the release of proinflammatory mediators (histamine, leukotrienes, and prostaglandins) from
immunoglobulin E (IgE)-sensitized effector cells (mast cells and basophils) when cell-bound IgE
antibodies interact with allergen. In vitro serum testing for IgE antibodies provides an indication of the
immune response to allergen(s) that may be associated with allergic disease. The allergens chosen for
testing often depend upon the age of the patient, history of allergen exposure, season of the year, and
clinical manifestations. In individuals predisposed to develop allergic disease(s), the sequence of
sensitization and clinical manifestations proceed as follows: eczema and respiratory disease (rhinitis and
bronchospasm) in infants and children less than 5 years due to food sensitivity (milk, egg, soy, and
wheat proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 227
and have been shown to cause accumulation of beta-catenin and subsequent activation of T-cell
factor-dependent transcription. These findings support the role of AXIN2 in tumorigenesis.
Useful For: Confirmation of oligodontia-colorectal cancer syndrome in patients with clinical features
Interpretation: All detected alterations will be evaluated according to American College of Medical
Genetics and Genomics (ACMG) recommendations.(1) Variants will be classified based on known,
predicted, or possible pathogenicity, and reported with interpretive comments detailing their potential or
known significance.
Reference Values:
An interpretive report will be provided.
Clinical References: 1.Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for
standards of interpretation and reporting of sequence variations: revisions 2007. Genet Med
2008:10(4):294-300 2. Lammi L, Arte S, Somer M, et al: Mutations in AXIN2 Cause Familial Tooth
Agenesis and Predispose to Colorectal Cancer. Am J Hum Genet 2004;74:1043-1050 3. Liu W, Dong X,
Mai M, et al: Mutations in AXIN2 cause colorectal cancer with defective mismatch repair by activating
beta-catenin/TCF signaling. Nat Genet 2000;26:146-147 4. Mai M, Qian C, Yokomizo A, et al: Cloning
of the human homolog of conductin (AXIN2), a gene mapping to chromosome 17q23-q24. Genomics
1998;55:341-344 5. Dong X, Seelan RS, Qian C, et al: Genomic structure, chromosome mapping and
expression analysis of the human AXIN2 gene. Cytogenet Cell Genet 2001;93:26-28
Azathioprine is measured as the metabolite, 6-mercaptopurine. Therapeutic and toxic ranges have not
been established. Usual therapeutic doses produce 6-mercaptopurine serum concentrations of less than
1000 ng/ml.
Useful For: Aids in monitoring a previously confirmed diagnosis of B-cell lymphoblastic leukemia
Interpretation: An interpretive report for presence or absence of B-cell lymphoblastic leukemia
(B-ALL) minimal residual disease (MRD) is provided. Patients who have detectable MRD by this assay
are considered to have residual/recurrent B-ALL.
Reference Values:
An interpretive report will be provided. This test will be processed as a laboratory consultation. An
interpretation of the immunophenotypic findings and correlation with the morphologic features will be
provided by a hematopathologist for every case.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 228
Clinical References: 1. Bader P, Kreyenberg H, Henze GH, et al: ALL-REZ BFM Study Group.
Prognostic value of minimal residual disease quantification before allogeneic stem-cell transplantation
in relapsed childhood acute lymphoblastic leukemia: The ALL-REZ BFM Study Group. J Clin Oncol
2009;27:377-384 2. Borowitz MJ, Devidas M, Hunger SP, et al; Children's Oncology Group. Clinical
significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship
to other prognostic factors: A Children's Oncology Group study. Blood 2008;111:5477-5485 3.
Borowitz MJ, Pullen DJ, Winick N, et al: Comparison of diagnostic and relapse flow cytometry
phenotypes in childhood acute lymphoblastic leukemia: implications for residual disease detection: a
report from the children's oncology group. Cytometry B Clin Cytom 2005;68:18-24 4. Campana D:
Role of minimal residual disease monitoring in adult and pediatric acute lymphoblastic leukemia.
Hematol Oncol Clin North Am 2009;23:1083-1098 5. Chen W, Karadikar NJ, McKenna RW, Kroft SH:
Stability of leukemia-associated immunophenoypes in precursor B-lymphoblastic leukemia/lymphoma.
a single institution experience. Am J Clin Pathol 2007;127:39-46 6. Coustan-Smith E, Ribeiro RC, Stow
P, et al: A simplified flow cytometric assay identifies children with acute lymphoblastic leukemia who
have a superior clinical outcome. Blood 2006;108:97-102 7. Coustan-Smith E, Sancho J, Behm FG, et
al: Prognostic importance of measuring early clearance of leukemic cells by flow cytometry in
childhood acute lymphoblastic leukemia. Blood 2002;100:52-58 8. Coustan-Smith E, Sancho J,
Hancock ML, et al: Clinical importance of minimal residual disease in childhood acute lymphoblastic
leukemia. Blood 2000;96:2691-2696 9. Guillaume N, Penther D, Vaida I, et al: CD66c expression in
B-cell lymphoblastic leukemia: strength and weakness. Int J Lab Hematol 2011;33:92-96 10. Lucio P,
Gaipa G, van Lochem EG, et al: BIOMED-I concerted action report: flow cytometric
immunophenotyping of precursor B-ALL with standardized triple-stainings. BIOMED-1 Concerted
Action Investigation of Minimal Residual Disease in Acute Leukemia: International Standardization
and Clinical Evaluation. Leukemia 2001;15:1185-1192 11. McKenna RW, Washington LT, Aquino DB,
et al: Immunophenotypic analysis of hematogones (B-lymphocyte precursors) in 662 consecutive bone
marrow specimens by 4-color flow cytometry. Blood 2001;98:2498-2507 12. Stow P, Key L, Chen X, et
al: Clinical significance of low levels of minimal residual disease at the end of remission induction
therapy in childhood acute lymphoblastic leukemia. Blood 2010;115:4657-4663 13. Weir EG, Cowan
K, LeBeau P, Borowitz MJ: A limited antibody panel can distinguish B-precursor acute lymphoblastic
leukemia from normal B precursors with four color flow cytometry: implications for residual disease
detection. Leukemia 1999;13:558-567
Useful For: Detecting a neoplastic clone associated with the common chromosome abnormalities seen
in patients with B-cell acute lymphoblastic leukemia (B-ALL) Identifying and tracking known
chromosome abnormalities in patients with B-ALL and tracking response to therapy As an adjunct to
conventional chromosome studies in patients with B-ALL
Interpretation: A neoplastic clone is detected when the percent of cells with an abnormality exceeds
the normal reference range for any given probe. The absence of an abnormal clone does not rule out the
presence of a neoplastic disorder.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Dewald GW, Ketterling RP: Conventional cytogenetics and molecular
cytogenetics in hematological malignancies. In Hematology. Basic Principles and Practice. Fourth edition.
Edited by R Hoffman, E Benz, S Shattil, et al. Philadelphia, Churchill Livingston, 2005, pp 928-939 2.
Pui CH, Relling MV, Downing JR: Acute lymphoblastic leukemia. N Engl J Med 2004
Apr;350(15):1535-1548 3. Swerdlow SH, Campo E, Harris NL, et al: WHO Classification of Tumours of
Haematopoietic and Lymphoid Tissues. Fourth edition. Lyon, France, IARC Press, 2008, 168-175 4.
Moorman AV, Harrison CJ, Buck GA, et al: Karyotype is an independent prognostic factor in adult acute
lymphoblastic leukemia (ALL): analysis of cytogenetic data from patients treated on the Medical
Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial. Blood
2007 Apr 15;109(8):3189-3197 5. Moorman, AV: The clinical relevance of chromosomal and genetic
abnormalities in B-cell precursor acute lymphoblastic leukemia. Blood Rev 2012;26:123-135
Useful For: Evaluating patients for hyper-IgM type 3 (HIGM3) syndrome due to defects in CD40,
typically seen in patients <10 years of age Assessing B-cell immune competence in other clinical
contexts, including autoimmunity, malignancy and transplantation
Interpretation: This assay is qualitative; CD40 expression is reported as present (normal) or absent
(abnormal). Normal B cells express surface CD40 on the majority of cells. Hyper-IgM (HIGM3)
syndrome patients typically do not express CD40 on the surface of B cells. Genotyping of CD40 is
required for a definite diagnosis of HIGM3. Contact Mayo Medical Laboratories for ordering
assistance.
Reference Values:
Present (normal)
Clinical References: Bishop GA, Hostager BS: The CD40-CD154 interaction in B cell-T cell
liaisons. Cytokine Growth Factor Rev 2003;14:297-309 2. Lee WI, Torgerson TR, Schumacher MJ, et
al: Molecular analysis of a large cohort of patients with hyper immunoglobulin M (IgM) syndrome.
Blood 2005;105:1881-1890 3. Kutukculer N, Moratto D, Aydinok Y, et al: Disseminated
cryptosporidium infection in an infant with hyper-IgM syndrome caused by CD40 deficiency. J Pediatr
2003;142:194-196 4. Ferrari S, Giliani S, Insalaco A, et al: Mutations of CD40 gene cause an autosomal
recessive form of immunodeficiency with hyper IgM. Proc Natl Acad Sci USA 2001;98:12614-12619
Useful For: Detecting a neoplastic clone associated with the common chromosome abnormalities
seen in patients with various B-cell lymphomas Tracking known chromosome abnormalities and
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 231
response to therapy in patients with B-cell neoplasms
Interpretation: A neoplastic clone is detected when the percent of cells with an abnormality exceeds
the normal reference range for any given probe. Detection of an abnormal clone supports a diagnosis of a
B-cell neoplasm; the specific abnormality detected may help subtype the neoplasm The absence of an
abnormal clone does not rule out the presence of neoplastic disorder.
Reference Values:
An interpretive report will be provided.
Useful For: Detecting a neoplastic clone associated with the common chromosome abnormalities seen
in patients with various B-cell lymphomas Tracking known chromosome abnormalities and response to
therapy in patients with B-cell lymphomas
Interpretation: A neoplastic clone is detected when the percent of cells with an abnormality exceeds
the normal reference range for any given probe. Detection of an abnormal clone is supportive of a
diagnosis of a B-cell lymphoma. The specific abnormality detected may help subtype the neoplasm. The
absence of an abnormal clone does not rule out the presence of a neoplastic disorder.
Reference Values:
An interpretive report will be provided.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 232
IABCS B-Cell Phenotyping Profile for Immunodeficiency and Immune
88800 Competence Assessment, Blood
Clinical Information: T- and B-Cell Quantitation by Flow Cytometry: Normal immunity requires a
balance between the activities of various lymphocyte subpopulations with different effector and
regulatory functions. Different immune cells can be characterized by unique surface membrane antigens
described by a cluster of differentiation nomenclature (eg, CD3 is an antigen found on the surface of T
lymphocytes). Abnormalities in the number and percent of T (CD3), T-helper (CD4), T-suppressor
(CD8), B (CD19), and natural killer (CD16+CD56) lymphocytes have been described in a number of
different diseases. In patients who are infected with HIV, the CD4 count is measured for AIDS
diagnosis and for initiation of antiviral therapy. The progressive loss of CD4 T lymphocytes in patients
infected with HIV is associated with increased infections and complications. The US Public Health
Service has recommended that all HIV-positive patients be tested every 3 to 6 months for the level of
CD4 T lymphocytes. The absolute counts of lymphocyte subsets are known to be influenced by a
variety of biological factors, including hormones, the environment, and temperature. The studies on
diurnal (circadian) variation in lymphocyte counts have demonstrated progressive increase in CD4
T-cell count throughout the day, while CD8 T cells and CD19+ B cells increase between 8:30 a.m. and
noon, with no change between noon and afternoon. Natural killer (NK) cell counts, on the other hand,
are constant throughout the day.(1) Circadian variations in circulating T-cell counts have been shown to
be negatively correlated with plasma cortisol concentration.(2-4) In fact, cortisol and catecholamine
concentrations control distribution and, therefore, numbers of naive versus effector CD4 and CD8 T
cells.(2) It is generally accepted that lower CD4 T-cell counts are seen in the morning compared with
the evening,(5) and during summer compared to winter.(6) These data, therefore, indicate that timing
and consistency in timing of blood collection is critical when serially monitoring patients for
lymphocyte subsets. Immune Assessment B Cell Subsets, Blood: The adaptive immune response
includes both cell-mediated (mediated by T cells and natural killer [NK] cells) and humoral immunity
(mediated by B cells). After antigen recognition and maturation in secondary lymphoid organs, some
antigen-specific B cells terminally differentiate into antibody-secreting plasma cells or become memory
B cells. Memory B cells are 3 subsets: marginal zone B cells (MZ or nonswitched memory),
class-switched memory B cells, and IgM-only memory B cells. Decreased B-cell numbers, B-cell
function, or both, result in immune deficiency states and increased susceptibility to infections. These
decreases may be either primary (genetic) or secondary. Secondary causes include medications,
malignancies, infections, and autoimmune disorders. Common variable immunodeficiency (CVID), a
disorder of B-cell function, is the most prevalent primary immunodeficiency with a prevalence of 1 to
25,000 to 1 to 50,000.(1) CVID has a bimodal presentation with a subset of patients presenting in early
childhood and a second set presenting between 15 and 40 years of age, or occasionally even later. Four
different genetic defects have been associated with CVID including mutations in the ICOS, CD19,
BAFF-R, and TACI genes. The first 3 genetic defects account for approximately 1% to 2%, and TACI
mutations account for 8% to 15% of CVID cases. CVID is characterized by hypogammaglobulinemia
usually involving most or all of the Ig classes (IgG, IgA, IgM, and IgE), impaired functional antibody
responses, and recurrent sinopulmonary infections.(1,2) B-cell numbers may be normal or decreased. A
minority of CVID patients (5%-10%) have very low B-cell counts (<1% of peripheral blood
leukocytes), while another subset (5%-10%) exhibit noncaseating, sarcoid-like granulomas in different
organs and also tend to develop a progressive T-cell deficiency.(1) Of all patients with CVID, 25% to
30% have increased numbers of CD8 T cells and a reduced CD4 to CD8 ratio (<1). Studies have shown
the clinical relevance of classifying CVID patients by assessing B-cell subsets, since changes in
different B-cell subsets are associated with particular clinical phenotypes or presentations.(3,4) The
B-cell phenotyping assay can be used in the diagnosis of hyper-IgM syndromes, which are characterized
by increased or normal levels of IgM with low IgG and/or IgA.(5) Patients with hyper-IgM syndromes
can have 1 of 5 known genetic defects-mutations in the CD40L, CD40, AID (activation-induced
cytidine deaminase), UNG (uracil DNA glycosylase), and NEMO (NF-kappa B essential modulator)
genes.(5) Mutations in CD40L and NEMO are inherited in an X-linked fashion, while mutations in the
other 3 genes are inherited in an autosomal recessive fashion. Patients with hyper-IgM syndromes have
a defect in isotype class-switching, which leads to a decrease in class-switched memory B cells, with or
without an increased in nonswitched memory B cells and IgM-only memory B cells. In addition to its
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 233
utility in the diagnosis of the above-described primary immunodeficiencies, B-cell phenotyping may be
used to assess reconstitution of B-cell subsets after hematopoietic stem cell or bone marrow transplant.
This test is also used to monitor B-cell-depicting therapies, such as Rituxan (Rituximab) and Zevalin
(Ibritumomab tiuxetan). CVID Confirmation Flow Panel: The etiology of CVID is heterogeneous, but
recently 4 genetic defects were described that are associated with the CVID phenotype. Specific
mutations, all of which are expressed on B cells, have been implicated in the pathogenesis of CVID.
These mutations encode for: -ICOS-inducible costimulator expressed on activated T cells(1)
-TACI-transmembrane activator and CAML (calcium modulator and cyclophilin ligand) interactor(2)
-CD19(3) -BAFF-R-B cell activating factor belonging to the tumor necrosis factor (TNF) receptor
family(4) Of these, the TACI mutations probably account for about 10% of all CVID cases.(2) Patients
with mutations in the TACI gene are particularly prone to developing autoimmune disease, including
cytopenias as well as lymphoproliferative disease. The other mutations each have been reported in only
a handful of patients. The etiopathogenesis is still undefined in more than 50% of CVID patients. A
BAFF-R defect should be suspected in patients with low to very low class switched and nonswitched
memory B cells and very high numbers of transitional B cells (see IABC/87994 B-Cell Phenotyping
Screen for Immunodeficiency and Immune Competence Assessment, Blood). Class switching is the
process that allows B cells, which possess IgD and IgM on their cell surface as a part of the
antigen-binding complex, to produce IgA, IgE, or IgG antibodies. A TACI defect is suspected in
patients with low IgM with normal to low switched B cells, with autoimmune and/or
lymphoproliferative manifestations, and normal B cell responses to mitogens. The absolute counts of
lymphocyte subsets are known to be influenced by a variety of biological factors, including hormones,
the environment, and temperature. The studies on diurnal (circadian) variation in lymphocyte counts
have demonstrated progressive increase in CD4 T-cell count throughout the day, while CD8 T cells and
CD19+ B cells increase between 8:30 a.m. and noon, with no change between noon and afternoon.
Natural killer (NK) cell counts, on the other hand, are constant throughout the day.(5) Circadian
variations in circulating T-cell counts have been shown to be negatively correlated with plasma cortisol
concentration.(6-8) In fact, cortisol and catecholamine concentrations control distribution and, therefore,
numbers of naive versus effector CD4 and CD8 T cells.(6) It is generally accepted that lower CD4
T-cell counts are seen in the morning compared with the evening,(9) and during summer compared to
winter.(10) These data, therefore, indicate that timing and consistency in timing of blood collection is
critical when serially monitoring patients for lymphocyte subsets.
Useful For: Screening for common variable immunodeficiency (CVID) and hyper-IgM syndromes
Assessing B-cell subset reconstitution after stem cell or bone marrow transplant Assessing response to
B-cell-depleting immunotherapy Identifying defects in transmembrane activator and calcium modulator
and cyclophilin ligand (CAML) interactor (TACI) and B-cell-activating factor receptor (BAFF-R) in
patients presenting with clinical symptoms and other laboratory features consistent with CVID
Interpretation: T- and B-Cell Quantitation by Flow Cytometry: When the CD4 count falls below 500
cells/mcL, HIV-positive patients can be diagnosed with AIDS and can receive antiretroviral therapy.
When the CD4 count falls below 200 cells/mcL, prophylaxis against Pneumocystis jiroveci pneumonia is
recommended. Immune Assessment B Cell Subsets, Blood: The assay provides quantitative information
on the various B-cell subsets (percentage and absolute counts in cells/microliter). Each specimen is
evaluated for B-cell subsets with respect to the total number of CD19+ B cells present in the peripheral
blood mononuclear cell population, compared to the reference range. In order to verify that there are no
CD19-related defects, CD20 is used as an additional pan-B-cell marker (expressed as percentage of
CD45+ lymphocytes). The B-cell panel assesses the following B-cell subsets: -CD19+=B cells expressing
CD19 as a percent of total lymphocytes -CD19+ CD27+=total memory B cells -CD19+ CD27+ IgD+
IgM+=marginal zone or nonswitched memory B cells -CD19+ CD27+ IgD- IgM+=IgM-only memory B
cells -CD19+ CD27+ IgD- IgM-=class-switched memory B cells -CD19+ IgM+=IgM B cells -CD19+
CD38+ IgM+=transitional B cells -CD19+ CD38+ IgM-=plasmablasts -CD19+ CD21-=CD21 low
("immature") B cells -CD19+ CD21+=mature B cells -CD19+ CD20+=B cells co-expressing both CD19
and CD20 as a percent of total lymphocytes For isotype class-switching and memory B-cell analyses, the
data will be reported as being consistent or not consistent with a defect in memory and/or class switching.
If a defect is present in any of these B-cell subpopulations, further correlation with clinical presentation
and additional functional, immunological, and genetic laboratory studies will be suggested. Since each of
the 11 B-cell subsets listed above contributes to the diagnosis of common variable immunodeficiency
(CVID) and hyper-IgM syndromes and provides further information on the likely specific genetic defect,
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 234
all the B-cell subsets are carefully evaluated to determine if further testing is needed for confirmation,
including functional assays and genotyping, which is then suggested as follow-up testing in the
interpretive report as detailed below. If abnormalities are found in the B-cell phenotyping panel, the
specimen will be reflexed to the CVID confirmation panel for assessment of defects in surface expression
of B-cell-activating factor receptor (BAFF-R) and transmembrane activator and calcium modulator and
cyclophilin ligand (CAML) interactor (TACI) (2 genes/proteins associated with CVID). To conclusively
determine if TACI mutations are present, the TACI mutation analysis test by gene sequencing can be
ordered (TACIF / Transmembrane Activator and CAML Interactor [TACI] Gene, Full Gene Analysis).
CVID Confirmation Flow Panel: BAFF-R is normally expressed on over 95% of B cells, while TACI is
expressed on a smaller subset of B cells and a proportion of activated T cells. The lack of TACI or
BAFF-R surface expression on the appropriate B-cell population is consistent with a CVID defect.
Results will be interpreted in the context of the B-cell phenotyping results and correlation to clinical
presentation will be recommended.
Reference Values:
The appropriate age-related reference values will be provided on the report.
Clinical References: T- and B-Cell Quantitation by Flow Cytometry: 1. Carmichael KF, Abayomi
A: Analysis of diurnal variation of lymphocyte subsets in healthy subjects and its implication in HIV
monitoring and treatment. 15th Intl Conference on AIDS, Bangkok, Thailand, 2004, Abstract B11052 2.
Dimitrov S, Benedict C, Heutling D, et al: Cortisol and epinephrine control opposing circadian rhythms
in T-cell subsets. Blood 2009;113(21):5134-5143 3. Dimitrov S, Lange T, Nohroudi K, Born J: Number
and function of circulating antigen presenting cells regulated by sleep. Sleep 2007;30:401-411 4.
Kronfol Z, Nair M, Zhang Q, et al: Circadian immune measures in healthy volunteers: relationship to
hypothalamic-pituitary-adrenal axis hormones and sympathetic neurotransmitters. Psychosom Med
1997;59:42-50 5. Malone JL, Simms TE, Gray GC, et al: Sources of variability in repeated T-helper
lymphocyte counts from HIV 1-infected patients: total lymphocyte count fluctuations and diurnal cycle
are important. J AIDS 1990;3:144-151 6. Paglieroni TG, Holland PV: Circannual variation in
lymphocyte subsets, revisited. Transfusion 1994;34:512-516 7. Mandy FF, Nicholson JK, McDougal
JS: Guidelines for performing single-platform absolute CD4+T-cell determinations with CD45 gating
for persons infected with human immunodeficiency virus. Center for Disease Control and Prevention.
MMWR Morb Mortal Wkly Rep 2003;52:1-13 8. Centers for Disease Control: 1997 Revised guidelines
for performing CD4+ T-cell determinations in persons infected with human immunodeficiency virus
(HIV). MMWR Morb Mortal Wkly Rep 46 no. RR-2: 1997, pp 1-29 9. U.S. Department of Health and
Human Services: Recommendations for prophylaxis against Pneumocystis carinii pneumonia for adults
and adolescents infected with human immunodeficiency virus. MMWR Morb Mortal Wkly Rep 43 no.
RR-3: 1994, pp 1-21 Immune Assessment B Cell Subsets, Blood: 1. Warnatz K, Denz A, Drager R, et
al: Severe deficiency of switched memory B cells (CD27+ IgM- IgD-) in subgroups of patients with
common variable immunodeficiency: a new approach to classify a heterogeneous disease. Blood
2002;99:1544-1551 2. Brouet JC, Chedeville A, Fermand JP, Royer B: Study of the B cell memory
compartment in common variable immunodeficiency. Eur J Immunol 2000;30:2516-2520 3. Wehr C,
Kivioja T, Schmitt C, et al: The EUROclass trial: defining subgroups in common variable
immunodeficiency. Blood 2008;111:77-85 4. Alachkar H, Taubenheim N, Haeney MR, et al: Memory
switched B-cell percentage and not serum immunoglobulin concentration is associated with clinical
complications in children and adults with specific antibody deficiency and common variable
immunodeficiency. Clin Immunol 2006;120:310-318 5. Lee WI, Torgerson TR, Schumacher MJ, et al:
Molecular analysis of a large cohort of patients with hyper immunoglobulin M (hyper IgM) syndrome.
Blood 2005;105:1881-1890 CVID Confirmation Flow Panel: 1. Grimbacher B, Hutloff A, Schlesier M,
et al: Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency.
Nat Immunol 2003;4(3):261-268 2. Salzer U, Chapel HM, Webster ADB, et al: Mutations in
TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans. Nat
Genet 2005;37(8):820-828 3. van Zelm M, Reisli I, van der Burg M, et al: An antibody-deficiency
syndrome due to mutations in the CD19 gene. New Engl J Med 2006;354:1901-1912 4. Warnatz K,
Salzer U, Gutenberger S, et al: Finally found: human BAFF-R deficiency causes
hypogammaglobulinemia. Clin Immunol 2005;115(Suppl 1):820 5. Carmichael KF, Abayomi A:
Analysis of diurnal variation of lymphocyte subsets in healthy subjects and its implication in HIV
monitoring and treatment. 15th Intl Conference on AIDS, Bangkok, Thailand, 2004, Abstract B11052 6.
Dimitrov S, Benedict C, Heutling D, et al: Cortisol and epinephrine control opposing circadian rhythms
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 235
in T-cell subsets. Blood 2009 (prepublished online March 17, 2009) 7. Dimitrov S, Lange T, Nohroudi
K, Born J: Number and function of circulating antigen presenting cells regulated by sleep. Sleep
2007;30:401-411 8. Kronfol Z, Nair M, Zhang Q, et al: Circadian immune measures in healthy
volunteers: relationship to hypothalamic-pituitary-adrenal axis hormones and sympathetic
neurotransmitters. Pyschosom Med 1997;59:42-50 9. Malone JL, Simms TE, Gray GC, et al: Sources of
variability in repeated T-helper lymphocyte counts from HIV 1-infected patients: total lymphocyte
count fluctuations and diurnal cycle are important. J AIDS 1990;3:144-151 10. Paglieroni TG, Holland
PV: Circannual variation in lymphocyte subsets, revisited. Transfusion 1994;34:512-516 11. Warnatz
K, Denz A, Drager R, et al: Severe deficiency of switched memory B cells (CD27+ IgM-IgD-) in
subgroups of patients with common variable immunodeficiency: a new approach to classify a
heterogeneous disease. Blood 2002;99:1544-1551
Useful For: Aids in the diagnosis of congestive heart failure (CHF) The role of brain natriuretic
peptide in monitoring CHF therapy is under investigation
Interpretation: >normal <200 pg/mL: likely compensated congestive heart failure (CHF) > or =200 to
< or =400 pg/mL: likely moderate CHF >400 pg/mL: likely moderate-to-severe CHF Brain natriuretic
peptide (BNP) levels are loosely correlated with New York Heart Association (NYHA) functional class
(see Table). Interpretive Levels for CHF Functional Class 5th to 95th Percentile Median I 15 to 499
pg/mL 95 pg/mL II 10 to 1,080 pg/mL 222 pg/mL III 38 to >1,300 pg/mL 459 pg/mL IV 147 to >1,300
pg/mL 1,006 pg/mL All CHF 22 to >1,300 pg/mL 360 pg/mL Elevation in BNP can occur due to right
heart failure with cor pulmonale (200-500 pg/mL), pulmonary hypertension (300-500 pg/mL), and acute
pulmonary embolism (150-500 pg/mL). Elevations also occur in patients with acute coronary syndromes.
Reference Values:
Males
< or =45 years: < or =35 pg/mL
46 years: < or =36 pg/mL
47 years: < or =37 pg/mL
48 years: < or =38 pg/mL
49 years: < or =39 pg/mL
50 years: < or =40 pg/mL
51 years: < or =41 pg/mL
52 years: < or =42 pg/mL
53 years: < or =43 pg/mL
54 years: < or =45 pg/mL
55 years: < or =46 pg/mL
56 years: < or =47 pg/mL
57 years: < or =48 pg/mL
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 236
58 years: < or =49 pg/mL
59 years: < or =51 pg/mL
60 years: < or =52 pg/mL
61 years: < or =53 pg/mL
62 years: < or =55 pg/mL
63 years: < or =56 pg/mL
64 years: < or =57 pg/mL
65 years: < or =59 pg/mL
66 years: < or =60 pg/mL
67 years: < or =62 pg/mL
68 years: < or =64 pg/mL
69 years: < or =65 pg/mL
70 years: < or =67 pg/mL
71 years: < or =69 pg/mL
72 years: < or =70 pg/mL
73 years: < or =72 pg/mL
74 years: < or =74 pg/mL
75 years: < or =76 pg/mL
76 years: < or =78 pg/mL
77 years: < or =80 pg/mL
78 years: < or =82 pg/mL
79 years: < or =84 pg/mL
80 years: < or =86 pg/mL
81 years: < or =88 pg/mL
82 years: < or =91 pg/mL
> or =83 years: < or =93 pg/mL
Females
< or =45 years: < or =64 pg/mL
46 years: < or =66 pg/mL
47 years: < or =67 pg/mL
48 years: < or =69 pg/mL
49 years: < or =71 pg/mL
50 years: < or =73 pg/mL
51 years: < or =74 pg/mL
52 years: < or =76 pg/mL
53 years: < or =78 pg/mL
54 years: < or =80 pg/mL
55 years: < or =82 pg/mL
56 years: < or =84 pg/mL
57 years: < or =87 pg/mL
58 years: < or =89 pg/mL
59 years: < or =91 pg/mL
60 years: < or =93 pg/mL
61 years: < or =96 pg/mL
62 years: < or =98 pg/mL
63 years: < or =101 pg/mL
64 years: < or =103 pg/mL
65 years: < or =106 pg/mL
66 years: < or =109 pg/mL
67 years: < or =112 pg/mL
68 years: < or =114 pg/mL
69 years: < or =117 pg/mL
70 years: < or =120 pg/mL
71 years: < or =123 pg/mL
72 years: < or =127 pg/mL
73 years: < or =130 pg/mL
74 years: < or =133 pg/mL
75 years: < or =137 pg/mL
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 237
76 years: < or =140 pg/mL
77 years: < or =144 pg/mL
78 years: < or =147 pg/mL
79 years: < or =151 pg/mL
80 years: < or =155 pg/mL
81 years: < or =159 pg/mL
82 years: < or =163 pg/mL
> or =83 years: < or =167 pg/mL
IgG: <1:64
IgM:<1:20
Elevated antibody levels to B. microti indicate exposure to the organism. Human babesiosis infection is
transmitted by the bite of an infected Ixodes tick or less frequently from transfusion with blood from an
infected donor. Definitive diagnosis is made by identifying intraerythrocytic organisms in peripheral
blood. In patients with low parasitemia, antibody detection by IFA is recommended. IgG levels greater
than or equal to 1:1024 can be detected in acute phase patients with parasites in blood smears. The IFA
assay can be used as a seroepidemiologic tool to study the frequency and distribution of B. microti in
endemic areas especially in persons with mixed infections also involving Borrelia burgdorferi.
Useful For: A serologic test can be used as an adjunct in the diagnosis of babesiosis or in
seroepidemiologic surveys of the prevalence of the infection in certain populations. Babesiosis is usually
diagnosed by observing the organisms in infected RBCs on Giemsa-stained thin blood films of smeared
peripheral blood. Serology may be useful if the parasitemia is too low to detect or if the infection has
cleared naturally or following treatment. Serology may also be useful in the follow-up of documented
cases of babesiosis or if chronic or persistent infection is suspected.
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Interpretation: A positive result of an indirect fluorescent antibody test (titer > or =1:64) suggests
current or previous infection with Babesia microti. In general, the higher the titer, the more likely it is
that the patient has an active infection. Patients with documented infections have usually had titers
ranging from 1:320 to 1:2,560.
Reference Values:
<1:64
Clinical References: Spach DH, Liles WC, Campbell GL, et al: Tick-borne diseases in the United
States. N Engl J Med 1993;329:936-947
Useful For: An initial screening or confirmatory testing method for suspected babesiosis during the
acute febrile stage of infection in patients from endemic areas, especially when Giemsa-stained
peripheral blood smears do not reveal any organisms or the organism morphology is inconclusive.
Interpretation: A positive result indicates the presence of Babesia species DNA and is consistent
with active or recent infection. While positive results are highly specific indicators of disease, they
should be correlated with blood smear microscopy, serological results and clinical findings. A negative
result indicates absence of detectable DNA from Babesia species in the specimen, but does not always
rule out ongoing babesiosis in a seropositive person, since the parasitemia may be present at a very low
level or may be sporadic. Other tests to consider in the evaluation of a patient presenting with an acute
febrile illness following tick exposure include serologic tests for Lyme disease (Borrelia burgdorferi),
and molecular detection (PCR) for ehrlichiosis/anaplasmosis. For patients who are past the acute stage
of infection, serologic tests for these organisms should be ordered prior to PCR testing.
Reference Values:
Negative
Clinical References: 1. Anderson JF, Mintz ED, Gadbaw JJ, et al: Babesia microti, human
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 239
babesiosis and Borrelia burgdorferi in Connecticut. J Clin Microbiol 1991;29(12):2779-2783 2.
Herwaldt BL, de Bruyn G, Pieniazek NJ, et al: Babesia divergens-like infection, Washington State.
Emerg Infect Dis 2004;10(4):622-629 3. Herwaldt B, Persing DH, Precigout EA, et al: A fatal case of
babesiosis in Missouri: identification of another piroplasm that infects humans. Ann Intern Med
1996;124(7):643-650 4. Homer MJ, Aguilar-Delfin I, Telford SR, et al: Babesiosis. Clin Microbiol Rev
2000;13(3):451-469 5. Thompson C, Spielman A, Krause PJ: Coinfecting deer-associated zoonoses:
Lyme disease, babesiosis, and ehrlichiosis. Clin Infect Dis 2001 Sept 1;33(5):676-685 6. Persing DH,
Herwaldt BL, Glaser C, et al: Infection with a Babesia-like organism in northern California. N Engl J
Med 1995;332(5):298-303 7. Quick RE, Herwaldt BL, Thomford JW, et al: Babesiosis in Washington
State: a new species of Babesia? Ann Intern Med 1993;119(4):284-290 8. Vannier E and Krause PJ:
Human Babesiosis. N Engl J Med 2012 Jun 21;366(25):2397-2407
Useful For: Detecting bacteria responsible for infections of sterile body fluids, tissues, or wounds
Interpretation: Any microorganism found where no resident flora is present is considered significant
and is reported. For specimens contaminated with the usual bacterial flora, bacteria that are potentially
pathogenic are identified.
Reference Values:
No growth or usual flora
Identification of probable pathogens
Clinical References: Forbes BA, Sahm DF, Weissfeld AS: Chapters 55, 56, 58, 60, 61. Bailey and
Scott's Diagnostic Microbiology. 12th edition. Mosby, St. Louis, MO, 2007
Useful For: An aid in the diagnosis of lower respiratory bacterial infections including pneumonia
Interpretation: Organisms associated with lower respiratory tract infections are reported.
Reference Values:
No growth or usual flora
Identification of probable pathogens
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Clinical References: 1. Chapter 2: Introduction to microbiology, Part II: Guidelines for the
Collection, Transport, Processing, Analysis and Reporting of cultures from Specific Specimen Sources.
In Konemans Color Atlas and Textbook of Diagnostic Microbiology. Seventh edition. Edited by:
GW Procop, DL Church, GS Hall, et al.. Philadelphia, Lippincott Williams and Wilkins, 2017, pp
66-110 2. York MK, Gilligan P, Alby K: Lower Respiratory Tract Cultures. In Clinical Microbiology
Procedures Handbook, Vol 1, Fourth edition. Edited by AL Leber. Washington DC, ASM Press, 2016,
Section 3.11.2
Useful For: Diagnosis of urinary tract infections Quantitative culture results may be helpful in
discriminating contamination, colonization, and infection.
Interpretation: In general, the isolation of more than 100,000 cfu/mL of a urinary pathogen is
indicative of urinary tract infection (UTI). Isolation of 2 or more organisms above 10,000 cfu/mL may
suggest specimen contamination. For specimens contaminated with the usual bacterial flora, bacteria
that are potentially pathogenic are identified.
Reference Values:
No growth or identification of probable pathogens with colony count ranges
Clinical References: Forbes BA, Sahm DF, Weissfeld AS: Infections of the urinary tract. In
Bailey and Scotts Diagnostic Microbiology. 12th edition. St. Louis, MO, Mosby, 2007, pp 842-855
Reference Values:
No growth
Identification of probable pathogens
Clinical References: 1. Summanen P, Baron EJ, Citron DM, et al. Wadsworth Anaerobic
Bacteriology Manual. Sixth edition. Belmont CA, Star Publishing Co, 2002 2. Chapters 50-54; Anaerobic
bacteria. In Manual of Clinical Microbiology, 11th edition. Edited by J Jorgensen, M Pfaller. Washington
DC, ASM Press, 2015 3. Hall GS, Section 4. Anaerobic bacteriology, In Clinical Microbiology
Procedures Handbook. Third edition. Edited by LS Garcia. Vol 1. ASM Press, Washington, DC. 2007
Useful For: Detection of aerobic bacterial pathogens from cystic fibrosis patient specimens
Interpretation: A negative test result is no growth of bacteria or growth of only usual flora. A negative
result does not rule out all causes of infectious lung disease (see Cautions). Organisms associated with
lower respiratory tract infections are reported. For positive test results, pathogenic bacteria are identified.
Cystic fibrosis patients may be colonized or chronically infected by some organisms over a long period of
time, therefore, positive results must be interpreted in conjunction with previous findings and the clinical
picture to appropriately evaluate results.
Reference Values:
No growth or usual flora
Identification of probable pathogens
Clinical References: 1. York MK, Gilligan P, Alby K: Lower Respiratory Tract Cultures. In Clinical
Microbiology Procedures Handbook, Vol 1, Fourth edition. Edited by AL Leber. Washington DC, ASM
Press, 2016, Section 3.11.2. 2. LiPuma JJ, Currie BJ, Peacock SJ, VanDamme PAR: Burkholderia,
Stenotrophomonas, Ralstonia, Cupriavidus, Pandoraea, Brevumndimonas, Comamonas, Delftia, and
Acidovorax. In Manual of Clinical Microbiology, Tenth edition. Edited by J Versalovic. Washington DC,
American Society for Microbiology Press, 2011, pp 692-713
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patterns. Antibiograms are often unreliable because they are easy to over-interpret or under-interpret.
Other strain-typing methods are often organism-specific and each requires a unique set of reagents and
procedures. The availability of classical strain-typing techniques has been limited. An excellent example
of the power of the technique was in the analysis of a large number of clustered isolates of
methicillin-resistant Staphylococcus aureus obtained from patients and staff at a Mayo Rochester hospital
during September and October, 1992. Although the high frequency with which this organism was isolated
suggested a nosocomial outbreak, molecular typing of the isolates showed: only 3 of the 14 were
identical; the remaining isolates were most likely the result of a surge in the number of random isolates of
this organism. Thus, the 14 isolates were not part of a nosocomial epidemic due to a single strain, and
radical measures for control of a nosocomial outbreak were unnecessary.
Useful For: Bacterial typing is useful to investigate infection outbreaks by a single species.
Interpretation: Isolates which show identical DNA restriction fragment length polymorphism
patterns are considered to be closely related.
Reference Values:
Reported as isolates from these sources are "indistinguishable" or "different" by pulsed-field gel
electrophoresis. Results will be faxed to the client.
Clinical References: 1. Arbeit RD, Arthur M, Dunn R, et al: Resolution of recent evolutionary
divergence among Escherichia coli from related lineages: the application of pulsed field electrophoresis
to molecular epidemiology. J Infect Dis 1990;161:230-235 2. Arbeit RD: Laboratory procedures for the
epidemiologic analysis of microorganisms. In Manual of Clinical Microbiology, Seventh edition. Edited
by PR Murray, ASM Press, Washington, DC, 1999, pp 116-137 3. Trees E, Rota RA, MacCannell D,
Gerner-Smidt P: Molecular epidemiology. In Manual of Clinical Microbiology, 11th edition. Edited by
J Jorgensen, ASM Press, Washington, DC, 2015, pp 131-160
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
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2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
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BCYP Bald Cypress, IgE
82722 Clinical Information: Clinical manifestations of immediate hypersensitivity (allergic) diseases are
caused by the release of proinflammatory mediators (histamine, leukotrienes, and prostaglandins) from
immunoglobulin E (IgE)-sensitized effector cells (mast cells and basophils) when cell-bound IgE
antibodies interact with allergen. In vitro serum testing for IgE antibodies provides an indication of the
immune response to allergens that may be associated with allergic disease. The allergens chosen for
testing often depend upon the age of the patient, history of allergen exposure, season of the year, and
clinical manifestations. In individuals predisposed to develop allergic disease, the sequence of
sensitization and clinical manifestations proceed as follows: eczema and respiratory disease (rhinitis and
bronchospasm) in infants and children less than 5 years due to food sensitivity (milk, egg, soy, and
wheat proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 245
wheat proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical utility
of food-specific IgG tests has not been established. These tests can be used in special clinical situations to
select foods for evaluation by diet elimination and challenge in patients who have food-related
complaints. It should be recognized that the presence of food-specific IgG alone cannot be taken as
evidence of food allergy and only indicates immunologic sensitization by the food allergen in question.
This test should only be ordered by physicians who recognize the limitations of the test.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 246
sensitization and clinical manifestations proceed as follows: eczema and respiratory disease (rhinitis and
bronchospasm) in infants and children less than 5 years due to food sensitivity (milk, egg, soy, and wheat
proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: As part of a panel of immunostains where loss of staining can be used as a marker of
various neoplasms
Interpretation: This test includes only technical performance of the stain (no pathologist
interpretation is performed). If diagnostic consultation by a pathologist is required order 70012 /
Pathology Consultation. The positive and negative controls are verified as showing appropriate
immunoreactivity. If a control tissue is not included on the slide, a scanned image of the relevant quality
control tissue is available upon request; contact 855-516-8404. Interpretation of this test should be
performed in the context of the patient's clinical history and other diagnostic tests by a qualified
pathologist.
Clinical References: 1. Carbone M, Ferris LK, Baumann F, et al: BAP1 cancer syndrome:
malignant mesothelioma, uveal and cutaneous melanoma, and MBAITS. J Transl Med 2012;10:179-185
2. Koopmans AE, Verdijk RM, Brouwer RWW, et al: Clinical significance of immunohistochemistry
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 247
for detection of BAP1 mutations in uveal melanoma. Mod Path 2014;27:1321-1330 3. Joseph RW,
Kapur P, Serie DJ, et al: Clear cell renal cell carcinoma subtypes identified by BAP1 and PBRM1
Expression. Jl of Urology 2015;195:1-8 4. Klebe S, Driml J, Nasu M, et al: BAP1 hereditary cancer
predisposition syndrome: a case report and review of literature. Biomark Res 2015;3:14-20 5. Mori T,
Sumii M, Fujishima F, et al: Somatic alteration and depleted nuclear expression of BAP1 in human
esophageal squamous cell carcinoma. Cancer Sci 2015;106:1118-1129 6. Churg A, Sheffield BS,
Galateau-Salle F: New markers for Separating Benign from Malignant Mesothelials: Are we there yet?
Arch Pathol Lab Med 2016;140(4):318-321
Useful For: Detecting drug abuse involving barbiturates such as amobarbital, butalbital, pentobarbital,
phenobarbital, and secobarbital Chain-of-custody is required whenever the results of testing could be used
in a court of law. Its purpose is to protect the rights of the individual contributing the specimen by
demonstrating that it was under the control of personnel involved with testing the specimen at all times;
this control implies that the opportunity for specimen tampering would be limited.
Interpretation: The presence of a barbiturate in urine at >200 ng/mL indicates use of 1 of these drugs.
Most of the barbiturates are fast acting; their presence indicates use within the past 3 days. Phenobarbital,
commonly used to control epilepsy, has a very long half-life. The presence of phenobarbital in urine
indicates that the patient has used the drug sometime within the past 30 days.
Reference Values:
Negative
Cutoff concentrations:
IMMUNOASSAY SCREEN
<200 ng/mL
BUTALBITAL BY GC-MS
<100 ng/mL
AMOBARBITAL BY GC-MS
<100 ng/mL
PENTOBARBITAL BY GC-MS
<100 ng/mL
SECOBARBITAL BY GC-MS
<100 ng/mL
PHENOBARBITAL BY GC-MS
<100 ng/mL
Clinical References: Baselt RC, Cravey RH: Disposition of Toxic Drugs and Chemicals in Man.
Third edition. Chicago, IL, Year Book Medical Publishers, 1989
Useful For: Detecting drug abuse involving barbiturates such as amobarbital, butalbital,
pentobarbital, phenobarbital, and secobarbital
Interpretation: The presence of a barbiturate in urine at >200 ng/mL indicates use of 1 of these
drugs. Most of the barbiturates are fast acting; their presence indicates use within the past 3 days.
Phenobarbital, commonly used to control epilepsy, has a very long half-life. The presence of
phenobarbital in urine indicates that the patient has used the drug sometime within the past 30 days.
Reference Values:
Negative
Cutoff concentrations:
BUTALBITAL BY GC-MS
<100 ng/mL
AMOBARBITAL BY GC-MS
<100 ng/mL
PENTOBARBITAL BY GC-MS
<100 ng/mL
SECOBARBITAL BY GC-MS
<100 ng/mL
PHENOBARBITAL BY GC-MS
<100 ng/mL
Clinical References: Baselt RC, Cravey RH: Disposition of Toxic Drugs and Chemicals in Man.
Third edition. Chicago, IL, Year Book Medical Publishers, 1989
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 249
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical utility
of food-specific IgG tests has not been established. These tests can be used in special clinical situations to
select foods for evaluation by diet elimination and challenge in patients who have food-related
complaints. It should be recognized that the presence of food-specific IgG alone cannot be taken as
evidence of food allergy and only indicates immunologic sensitization by the food allergen in question.
This test should only be ordered by physicians who recognize the limitations of the test.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 250
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
4 17.5-49.9 Strongly positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
INTERPRETIVE CRITERIA:
<1:1 Antibody Not Detected
> or = 1:1 Antibody Detected
Infection with Bartonella henselae has been associated with cat scratch disease, bacillary angiomatosis,
peliosis hepatis and febrile bacteremia syndrome. Infection with Bartonella quintana has been
associated with trench fever and bacillary angiomatosis in both HIV positive and negative individuals.
IgG crossreactivity between B. henselae and B. Quintana may occur at any titer; however, the infecting
species will typically have the higher IgG titer. Crossreactivity of IgM between the two species is
limited and typically is not seen.
Diagnosis of infections of the central nervous system can be accomplished by demonstrating the
presence of intrathecally-produced specific antibody. However, interpreting results is complicated by
low antibody levels found in CSF, passive transfer of antibody from blood, and contamination via
bloody taps.
Useful For: Rapid diagnosis of Bartonella infection, especially in the context of a cat scratch or
histopathology showing typical features of stellate microabscesses and/or positive Warthin-Starry stain
Interpretation: A positive immunofluorescence assay (IFA) IgM (titer >1:20) suggests a current
infection with either Bartonella henselae or Barteonella quintana. A positive IgG (titer >1:128) suggests a
current or previous infection. Increases in IgG titers in serial specimens would indicate an active infection.
Normal serum specimens usually have an IgG titer of <1:128. However, 5% to 10% of healthy controls
exhibit a Bartonella henselae and Bartonella quintana titer of 1:128. No healthy controls showed titers of
> or =1:256. IgM titers from normal serum were found to be <1:20. IgM titers at > or =1:20 have not been
seen in the normal population. Culture should also be considered, but this may not be an optimal method
due to slow growth and fastidious nature of the organism.
Reference Values:
Bartonella henselae
IgG: <1:128
IgM: <1:20
Bartonella quintana
IgG: <1:128
IgM: <1:20
Reference Values:
Not applicable
Clinical References: 1. Karem KL, Paddock CD, Regnery RL: Bartonella henselae, B. quintana,
and B. bacilliformis: historical pathogens of emerging significance. Microbes Infect 2000
August;2(10):1193-1205 2. Agan BK, Dolan MJ: Laboratory diagnosis of Bartonella infections. Clin
Lab Med 2002 December;22(4):937-962 3. Maguina C, Gotuzzo E: Bartonellosis. New and old. Infect
Dis Clin North Am 2000 March;14(1):1-22 4. Vikram HR, Bacani AK, Devaleria PA, et al: Bivalvular
Bartonella henselae prosthetic valve endocarditis. J Clin Microbiol 2007 December;45(12):4081-4084
5. Lin EY, Tsigrelis C, Baddour LM, et al: Candidatus Bartonella mayotimonensis and endocarditis.
Emerg Infect Dis 2010 Mar;16(3):500-503
Useful For: Diagnosing Bartonella infection where Bartonella DNA would be expected to be present
in blood, especially endocarditis
Interpretation: A positive test indicates the presence of Bartonella species DNA. A negative test
indicates the absence of detectable DNA, but does not negate the presence of the organism or recent
disease as false-negative results may occur due to inhibition of PCR, sequence variability underlying
primers and probes, or the presence of Bartonella DNA in quantities less than the limit of detection of
the assay.
Reference Values:
Not applicable
Clinical References: 1. Karem KL, Paddock CD, Regnery RL: Bartonella henselae, B. quintana,
and B. bacilliformis: historical pathogens of emerging significance. Microbes Infect 2000
August;2(10):1193-1205 2. Agan BK, Dolan MJ: Laboratory diagnosis of Bartonella infections. Clin
Lab Med 2002 December;22(4):937-962 3. Maguina C, Gotuzzo E: Bartonellosis. New and old. Infect
Dis Clin North Am 2000 March;14(1):1-22 4. Vikram HR, Bacani AK, Devaleria PA, et al: Bivalvular
Bartonella henselae prosthetic valve endocarditis. J Clin Microbiol 2007 December;45(12):4081-4084
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical utility
of food-specific IgG tests has not been established. These tests can be used in special clinical situations to
select foods for evaluation by diet elimination and challenge in patients who have food-related
complaints. It should be recognized that the presence of food-specific IgG alone cannot be taken as
evidence of food allergy and only indicates immunologic sensitization by the food allergen in question.
This test should only be ordered by physicians who recognize the limitations of the test.
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 254
FBBLE Bass Black (Sea Bass) (Centropristis striata) IgE
57546 Interpretation: Class IgE(kU/L) Comment 0 <0.35 Below Detection 1 0.35 - 0.69 Low Positive 2
0.70 3.49 Moderate Positive 3 3.50 17.49 Positive 4 17.50 49.99 Strong Positive 5 50.00
99.99 Very Strong Positive 6 >99.99 Very Strong Positive
Reference Values:
<0.35 kU/L
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Reference Values:
<0.35 kU/L
Clinical References: 1. Choi WW, Weisenburger DD, Greiner TC, et al: A new immunostain
algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy. Clin
Cancer Res 2009;15:5594-5502 2. Hu S, Xu-Monette ZY, Tzankov A, et al: MYC/BCL2 protein
coexpression contributes to the inferior survival of activated B-cell subtype of diffuse large B-cell
lymphoma and demonstrates high-risk gene expression signatures: a report from The International
DLBCL Rituximab-CHOP Consortium Program. Blood 2013;121(20):4021-4031 3. Iqbal J, Neppalli VT,
Wright G, et al: BCL2 expression is a prognostic marker for the activated B-cell-like type of diffuse large
B-cell lymphoma. J Clin Oncol 2006;24(6):961-968
Clinical References: 1. Choi WW, Weisenburger DD, Greiner TC, et al: A new immunostain
algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy. Clin
Cancer Res 2009;15:5594-5502 2. Dogan A, Bagdi E, Munson P, Isaacson PG: CD10 and BCL-6
expression in paraffin sections of normal lymphoid tissue and B-cell lymphomas. Am J Surg Pathol
2000;24(6):846-852 3. Gualco G, Weiss LM, Harrington WJ Jr, Bacchi CE: BCL6, MUM1, and CD10
expression in mantle cell lymphoma. Appl Immunohistochem Mol Morphol 2010;18(2):103-108
Useful For: Monitoring response to therapy in patients with known e1/a2 bcr/abl (p190) fusion forms
Interpretation: An interpretive report will be provided.
Reference Values:
The presence or absence of the BCR/ABL mRNA (bcr/abl) fusion form producing the p190 fusion
protein is reported. If positive, the level is reported as the ratio of bcr/abl (p190) to abl with conversion
to a percentage (ie, bcr/abl (p190) as a percentage of total abl).
Clinical References: 1. Hughes TP, Kaeda J, Branford S, et al: Frequency of major molecular
responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia. N
Engl J Med 2003;349:1423-1432 2. Radich JP, Gooley T, Bryant E, et al: The significance of
BCR/ABL molecular detection in chronic myeloid leukemia patients "late," 18 months or more after
transplantation. Blood 2001;98:1701-1707 3. Olavarria E, Kanfer E, Szydlo R, et al: Early detection of
BCR-ABL transcripts by quantitative reverse transcriptase-polymerase chain reaction predicts outcome
after allogeneic stem cell transplant for chronic myeloid leukemia. Blood 2001;97:1560-1565
Useful For: Detecting a neoplastic clone associated with a BCR/ABL1 rearrangement in patients
with chronic myeloid leukemia (CML) Tracking the percentage of nuclei with BCR/ABL1
rearrangement and response to therapy in patients with CML.
Interpretation: A neoplastic clone is detected when the percent of cells with an abnormality exceeds
the normal reference range. Additional cells are analyzed to assess minimal residual disease (MRD).
The absence of an abnormal clone does not rule out the presence of neoplastic disorder.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 257
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Dewald GW, Wyatt WA, Silver RT: Atypical BCR and ABL D-FISH
patterns in chronic myeloid leukemia and their possible role in therapy. Leuk Lymphoma
1999;34(5-6):481-491 2. Dewald GW, Juneau AL, Schad CR, Tefferi A: Cytogenetic and molecular
genetic methods for diagnosis and treatment response in chronic granulocytic leukemia. Cancer Genet
Cytogenet 1997;94:59-66 3. The Italian Cooperative Study Group on Chronic Myeloid Leukemia:
Interferon alpha-2a as compared with conventional chemotherapy for the treatment of chronic myeloid
leukemia. N Engl J Med 1994;330:820-825 4. Dewald GW: Interphase FISH studies for chronic myeloid
leukemia. In Methods in Molecular Biology. Vol 204. Molecular Cytogenetics: Protocols and
Applications. Edited by YS Fan. Totowa, NJ, Humana Press, USA, 2002 pp 311-342
Useful For: Monitoring response to therapy in patients with chronic myeloid leukemia who are known
to have the e13/a2 or e14/a2 BCR/ABL1 fusion transcript forms
Reference Values:
The presence or absence of BCR/ABL1 mRNA fusion form e13/e14-a2 producing the p210 fusion protein
is identified. If positive, the quantitative level is reported as the normalized ratio of BCR/ABL1 (p210) to
endogenous ABL1 mRNA with conversion to a percentage referenced to the international scale (IS), on
which 0.1% BCR/ABL1:ABL1 (also represented on a log scale as Molecular Response 3, or MR3) is
designated as a major molecular response (MMR) threshold.
Clinical References: 1. Hughes TP, Kaeda J, Branford S, et al: Frequency of major molecular
responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia. N
Engl J Med 2003 October 9;349(15):1423-1432 2. Baccarini M, Deininger MW, Rosti G, et al: European
LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood
2013;122:872-884 3. Press RD, Kamel-Reid S, Ang D: BCR-ABL1 RT-qPCR for monitoring the
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 258
molecular response to tyrosine kinase inhibitors in chronic myeloid leukemia. J Mol Diagn
2013;15:565-576 4. Cross NC, White HE, Muller MC, et al: Standardized definitions of molecular
response in chronic myeloid leukemia. Leukemia 2012;26:2172-2175 5. National Comprehensive Cancer
Network Practice Guidelines in Oncology: Chronic Myeloid Leukemia 2015 (https://www.nccn.org)
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 259
BAKDM BCR/ABL1, Tyrosine Kinase Inhibitor Resistance, Kinase
89609 Domain Mutation Screen, Sanger Sequencing
Clinical Information: Chronic myelogenous leukemia (CML) is characterized by the presence of the
t(9:22) BCR-ABL1 abnormality, resulting in formation of a fusion BCR-ABL1 mRNA and protein. The
ABL1 component of this oncoprotein contains tyrosine kinase activity and is thought to play a central role
in the proliferative phenotype of this leukemia. Recent advances have resulted in a number of therapeutic
drugs that inhibit the ABL1 tyrosine kinase, as well as other protein tyrosine kinases. Imatinib mesylate
(Gleevec, Novartis) is the prototype of these tyrosine kinase inhibitors (TKIs), which are capable of
inducing durable hematologic and (in most patients) cytogenetic remissions. Unfortunately, a significant
subset of patients can develop functional resistance to TKIs, due in a large number of cases
(approximately 50%) to the acquisition of point mutations in the kinase domain (KD) of the chimeric
ABL1 gene. To date, over 50 distinct mutations have been described, although a smaller subset of these
(<20) account for the majority of patients with clinical resistance to TKIs, or have well documented in
vitro data in the published literature. Recognition of TKI resistance is important in CML, as the effect of
some mutations can be overcome by increasing imatinib dosage, whereas others require switching to
either a different (second-generation) TKI, or alternative therapy. The common T315I KD mutation is
particularly important, given that this alteration confers pan-resistance to all currently employed TKIs
except ponatinib. Typically, TKI resistance is suspected in a CML patient who shows loss of initial
therapeutic response (eg, cytogenetic relapse), or a significant and sustained increase in molecular
BCR-ABL1 quantitative levels. Similar considerations are also present in patients with Philadelphia
chromosome positive B-cell acute lymphoblastic leukemia, who can also be treated using TKI therapy.
Point mutations in the oncogenic BCR-ABL1 are typically detected by direct sequencing of PCR
products, following RT-PCR amplification of the BCR-ABL mRNA transcript from a peripheral blood
specimen. This approach ensures comprehensive screening of the clinically relevant KD region. Because
this technique requires inclusion of a longer region of ABL1 in the BCR-ABL1 RT-PCR product, low
levels of the BCR-ABL1 mRNA transcript (below 0.01% normalized BCR-ABL1 on the International
Scale, IS) may not be efficiently amplified (in contrast to similar amplicons generated by quantitative
RT-PCR for diagnosis or monitoring).
Useful For: Evaluating patients with chronic myelogenous leukemia and Philadelphia chromosome
positive B-cell acute lymphoblastic leukemia receiving tyrosine kinase inhibitor (TKI) therapy, who are
apparently failing treatment This is the preferred initial test to identify the presence of acquired
BCR-ABL1 mutations associated with TKI-resistance.
Interpretation: The presence of 1 or more point mutations in the translocated portion of the ABL1
region of the BCR-ABL1 fusion mRNA is considered a positive result, indicating tyrosine kinase
inhibitor (TKI) resistance. The specific type of mutation may influence the sensitivity to a specific TKI,
and could be useful in guiding therapeutic options for an individual patient.
Reference Values:
An interpretive report will be provided.
Reference Values:
<0.35 kU/L
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical
utility of food-specific IgG tests has not been established. These tests can be used in special clinical
situations to select foods for evaluation by diet elimination and challenge in patients who have
food-related complaints. It should be recognized that the presence of food-specific IgG alone cannot be
taken as evidence of food allergy and only indicates immunologic sensitization by the food allergen in
question. This test should only be ordered by physicians who recognize the limitations of the test.
Reference Values:
<2 mcg/mL
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical
utility of food-specific IgG tests has not been established. These tests can be used in special clinical
situations to select foods for evaluation by diet elimination and challenge in patients who have
food-related complaints. It should be recognized that the presence of food-specific IgG alone cannot be
taken as evidence of food allergy and only indicates immunologic sensitization by the food allergen in
question. This test should only be ordered by physicians who recognize the limitations of the test.
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical
utility of food-specific IgG tests has not been established. These tests can be used in special clinical
situations to select foods for evaluation by diet elimination and challenge in patients who have
food-related complaints. It should be recognized that the presence of food-specific IgG alone cannot be
taken as evidence of food allergy and only indicates immunologic sensitization by the food allergen in
question. This test should only be ordered by physicians who recognize the limitations of the test.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 261
Reference Values:
<0.35 kU/L
Reference Values:
<0.35 kU/L
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical utility
of food-specific IgG tests has not been established. These tests can be used in special clinical situations to
select foods for evaluation by diet elimination and challenge in patients who have food-related
complaints. It should be recognized that the presence of food-specific IgG alone cannot be taken as
evidence of food allergy and only indicates immunologic sensitization by the food allergen in question.
This test should only be ordered by physicians who recognize the limitations of the test.
Clinical References: 1. DeBaun MR, Niemitz EL, McNeil DE, et al: Epigenetic alterations of H19
and LIT1 distinguish patients with Beckwith-Wiedemann Syndrome with cancer and birth defects. Hum
Genet 2002;70:604-611 2. Choufani S, Shuman C, Weksberg R: Beckwith-Wiedemann Syndrome. Am
J of Med Genet 2010;154C:343-354 3. Wakeling EL: Silver-Russell syndrome. Arch Dis Child
2011;96(12):1156-1161 4. Eggermann T, Begemann M, Binder G, et al: Silver-Russell syndrome:
genetic basis and molecular genetic testing. Orphanet J Rare Dis 2010;5:19-26 5. Priolo M, Sparago A,
Mammi C, et al: MS-MLPA is a specific and sensitive technique for detecting all chromosome 11p15.5
imprinting defects of BWS and SRS in a single-tube experiment. Eur J Hum Genet 2008;16:565-571
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 263
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical utility
of food-specific IgG tests has not been established. These tests can be used in special clinical situations to
select foods for evaluation by diet elimination and challenge in patients who have food-related
complaints. It should be recognized that the presence of food-specific IgG alone cannot be taken as
evidence of food allergy and only indicated immunologic sensitization by the food allergen in question.
This test should only be ordered by physicians who recognize the limitations of the test.
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 264
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 265
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical utility
of food-specific IgG tests has not been established. These tests can be used in special clinical situations to
select foods for evaluation by diet elimination and challenge in patients who have food-related
complaints. It should be recognized that the presence of food-specific IgG alone cannot be taken as
evidence of food allergy and only indicates immunologic sensitization by the food allergen in question.
This test should only be ordered by physicians who recognize the limitations of the test.
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 266
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Phenol: mg/L
Phenol: mg/G creat
Exposed:
Biological Exposure Index (BEI): 50 mg/g creatinine (End of Shift)
Toxic:
Not Established
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 267
and anxiolytic agents. Chain of custody is a record of the disposition of a specimen to document who
collected it, who handled it, and who performed the analysis. When a specimen is submitted in this
manner, analysis will be performed in such a way that it will withstand regular court scrutiny.
Useful For: Detecting drug use involving benzodiazepines such as alprazolam, flunitrazepam,
chlordiazepoxide, diazepam, flurazepam, lorazepam, and triazolam Chain of custody is required whenever
the results of testing could be used in a court of law. Its purpose is to protect the rights of the individual
contributing the specimen by demonstrating that it was under the control of personnel involved with
testing the specimen at all times; this control implies that the opportunity for specimen tampering would
be limited.
Interpretation: Benzodiazepines are extensively metabolized, and the parent compounds are not
detected in urine. This test screens for (and confirms) the presence of: -Nordiazepam, oxazepam
(metabolites of chlordiazepoxide) -Nordiazepam, oxazepam and temazepam (metabolites of diazepam)
-Lorazepam -Hydroxyethylfluorazepam (metabolite of flurazepam) -Alpha hydroxyalprazolam
(metabolite of alprazolam) -Alpha hydroxytriazolam (metabolite of triazolam) -7-Aminoclonazepam
(metabolite of clonazepam) -7-Aminoflunitrazepam (metabolite of flunitrazepam) The clearance half-life
of long-acting benzodiazepines is >24 hours. It takes 5 to 7 half-lives to clear 98% of a drug dose.
Therefore, the presence of a long-acting benzodiazepine greater than the limit of quantification indicates
exposure within a 5- to 20-day interval preceding specimen collection. Following a dose of diazepam, the
drug and its metabolites appear in the urine within 30 minutes. Peak urine output is reached between 1 and
8 hours. See Mayo Medical Laboratories Drugs of Abuse Testing Guide at
http://www.mayomedicallaboratories.com/test-info/drug-book/index.html for additional information
including metabolism, clearance (half-life), and approximate detection times.
Reference Values:
Negative
Cutoff concentrations:
IMMUNOASSAY SCREEN
<100 ng/mL
NORDIAZEPAM BY GC-MS
<100 ng/mL
OXAZEPAM BY GC-MS
<100 ng/mL
LORAZEPAM BY GC-MS
<100 ng/mL
TEMAZEPAM BY GC-MS
<100 ng/mL
OH-ETHYL-FLURAZEPAM BY GC-MS
<100 ng/mL
7-NH-CLONAZEPAM BY GC-MS
<100 ng/mL
7-NH-FLUNITRAZEPAM BY GC-MS
<50 ng/mL
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 268
Clinical References: 1. Disposition of Toxic Drugs and Chemicals in Man. Eighth edition. Edited
by RC Baselt. Foster City, CA: Biomedical Publications, 2008 2. Porter W: Clinical toxicology. In Tietz
Textbook of Clinical Chemistry. Fourth edition. Edited by CA Burtis, DE Bruns. St. Louis, MO.
Elsevier Saunders, 2006, pp 1287-1369
Useful For: Detecting drug use involving benzodiazepines such as alprazolam, flunitrazepam,
chlordiazepoxide, diazepam, flurazepam, lorazepam, and triazolam
Interpretation: Benzodiazepines are extensively metabolized, and the parent compounds are not
detected in urine. This test screens for (and confirms) the presence of: -Nordiazepam, oxazepam
(metabolites of chlordiazepoxide) -Nordiazepam, oxazepam and temazepam (metabolites of diazepam)
-Lorazepam -Hydroxyethylfluorazepam (metabolite of flurazepam) -Alpha hydroxyalprazolam
(metabolite of alprazolam) -Alpha hydroxytriazolam (metabolite of triazolam) -7-aminoclonazepam
(metabolite of clonazepam) -7-aminoflunitrazepam (metabolite of flunitrazepam) The clearance half-life
of long-acting benzodiazepines is more than 24 hours. It takes 5 to 7 half-lives to clear 98% of a drug
dose. Therefore, the presence of a long-acting benzodiazepine greater than the limit of quantification
indicates exposure within a 5 to 20-day interval preceding specimen collection. Following a dose of
diazepam, the drug and its metabolites appear in the urine within 30 minutes. Peak urine output is
reached between 1 and 8 hours. See Mayo Medical Laboratories Drugs of Abuse Testing Guide at
http://www.mayomedicallaboratories.com/test-info/drug-book/index.html for additional information
including metabolism, clearance (half-life), and approximate detection times.
Reference Values:
Negative
Cutoff concentrations:
NORDIAZEPAM BY GC-MS
<100 ng/mL
OXAZEPAM BY GC-MS
<100 ng/mL
LORAZEPAM BY GC-MS
<100 ng/mL
TEMAZEPAM BY GC-MS
<100 ng/mL
OH-ETHYL-FLURAZEPAM BY GC-MS
<100 ng/mL
7-NH-CLONAZEPAM BY GC-MS
<100 ng/mL
7-NH-FLUNITRAZEPAM BY GC-MS
<50 ng/mL
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 269
ALPHA OH-TRIAZOLAM BY GC-MS
<100 ng/mL
Clinical References: 1. Disposition of Toxic Drugs and Chemicals in Man. Eighth edition. Edited by
RC Baselt. Foster City, CA: Biomedical Publications, 2008 2. Porter W: Clinical toxicology. In Tietz
Textbook of Clinical Chemistry. Edited by CA Burtis, DE Bruns. Fourth edition. St. Louis, MO. Elsevier
Saunders, 2006, pp 1287-1369
Useful For: An aid in distinguishing basal cell carcinoma from squamous cell carcinoma of the skin
An aid in distinguishing pulmonary adenocarcinoma from mesothelioma
Interpretation: This test includes only technical performance of the stain (no pathologist interpretation
is performed). If diagnostic consultation by a pathologist is required, order 70012 / Pathology
Consultation. The positive and negative controls are verified as showing appropriate immunoreactivity. If
a control tissue is not included on the slide, a scanned image of the relevant quality control tissue is
available upon request; contact 855-516-8404. Interpretation of this test should be performed in the
context of the patient's clinical history and other diagnostic tests by a qualified pathologist.
Clinical References: 1. Beer TW, Shepherd P, Theaker JM: Ber EP4 and epithelial membrane
antigen aid distinction of basal cell, squamous cell and basosquamous carcinomas of the skin.
Histopathology 2000;37:218-223 2. Ordonez NG: The diagnostic utility of immunohistochemistry in
distinguishing between epithelioid mesotheliomas and squamous carcinomas of the lung: A comparative
study. Mod Pathol 2006;19(3):417-428 3. Sheibani K, Shin SS, Kezirian J, et al: Ber-EP4 antibody as a
discriminant in the differential diagnosis of malignant mesothelioma versus adenocarcinoma. Am J Surg
Pathol 1991;15(8):779-784
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 270
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 271
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Diagnosis of beta thalassemia intermedia or major Identification of a specific beta
thalassemia mutation (ie, unusually severe beta thalassemia trait) Evaluation of an abnormal
hemoglobin electrophoresis identifying a rare beta globin variant Evaluation of chronic hemolytic
anemia of unknown etiology Evaluation of hereditary erythrocytosis with left-shifted p50 oxygen
dissociation results Preconception screening when there is a concern for a beta hemoglobin disorder
based on family history
Interpretation: The alteration will be provided with the classification, if known. Further
interpretation requires correlation with protein studies and RBC indices.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Hoyer JD, Hoffman DR: The thalassemia and hemoglobinopathy
syndromes. In Clinical Laboratory Medicine. Second edition. Edited by KD McClatchey. Philadelphia,
Lippincott Williams and Wilkins, 2002, pp 866-895 2. Thein SL: The Molecular Basis of
Beta-Thalassemia. Cold Spring Harb Persepct Med 2013;1;3(5):a011700 3. Hoyer JD, Kroft, SH: Color
Atlas of Hemoglobin Disorders: A Compendium Based on Proficiency Testing. Northfield, IL. CAP,
2003 4. Merchant S, Oliveira JL, Hoyer JD, Viswanatha DS: Molecular diagnosis in hematopathology.
In Hematopathology: A Volume in Foundations in Diagnostic Pathology Series. Second edition Edited
by J Goldblum. Volume Editor E Hsi. Churchill Livingstone, 2012
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical
utility of food-specific IgG tests has not been established. These tests can be used in special clinical
situations to select foods for evaluation by diet elimination and challenge in patients who have
food-related complaints. It should be recognized that the presence of food-specific IgG alone cannot be
taken as evidence of food allergy and only indicates immunologic sensitization by the food allergen in
question. This test should only be ordered by physicians who recognize the limitations of the test.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 273
functional coagulation assays. Immunoassays for beta-2 GP1 antibodies can be performed using either a
composite substrate comprised of beta-2 GP1 plus anionic phospholipid (eg, cardiolipin or
phosphatidylserine), or beta-2 GP1 alone. Antibodies detected by immunoassays that utilize composite
substrates are commonly referred to as phospholipid or cardiolipin antibodies. Antibodies detected
using beta-2 GP1 substrate without phospholipid (so called direct assays) are referred to simply as
"beta-2 GP1 antibodies." Some beta-2 GP1 antibodies are capable of inhibiting clot formation in
functional coagulation assays that contain low concentrations of phospholipid cofactors. Antibodies
detected by functional coagulation assays are commonly referred to as lupus anticoagulants. The
diagnosis of APS requires at least 1 clinical criteria and 1 laboratory criteria be met.(5) The clinical
criteria include vascular thrombosis (arterial or venous in any organ or tissue) and pregnancy morbidity
(unexplained fetal death, premature birth, severe preeclampsia, or placental insufficiency). Other
clinical manifestations, including heart valve disease, livedo reticularis, thrombocytopenia,
nephropathy, neurological symptoms, are often associated with APS, but are not included in the
diagnostic criteria. The laboratory criteria for diagnosis of APS are the presence of lupus anticoagulant,
the presence of IgG and/or IgM anticardiolipin antibody (>40 GPL, >40 MPL or >99th percentile),
and/or the presence of IgG and/or IgM beta-2 GP1 antibody (>99th percentile). All antibodies must be
demonstrated on 2 or more occasions separated by at least 12 weeks. Direct assays for beta-2GP 1
antibodies have been reported to be somewhat more specific (but less sensitive) for disease diagnosis in
patients with APS.(4) Anticardiolipin and beta-2 GP1 antibodies of the IgA isotype are not part of the
laboratory criteria for APS due to lack of specificity.
Interpretation: Strongly positive results for IgG and IgM beta-2 glycoprotein 1 (beta-2 GP1)
antibodies (>40 U/mL for IgG and/or IgM) are diagnostic criterion for antiphospholipid syndrome (APS).
Lesser levels of beta-2 GP1 antibodies and antibodies of the IgA isotype may occur in patients with
clinical signs of APS, but the results are not considered diagnostic. Beta-2 GP1 antibodies must be
detected on 2 or more occasions at least 12 weeks apart to fulfill the laboratory diagnostic criteria for
APS. IgA beta-2 GP1 antibody result >15 U/mL with negative IgG and IgM beta-2 GP1 antibody results
are not diagnostic for APS. Detection of beta-2 GP1 antibodies is not affected by anticoagulant treatment.
Reference Values:
<15.0 U/mL (negative)
15.0-39.9 U/mL (weakly positive)
40.0-79.9 U/mL (positive)
> or =80.0 U/mL (strongly positive)
Results are expressed in arbitrary units.
Reference values apply to all ages.
Interpretation: Strongly positive results for beta-2 glycoprotein 1 (beta-2 GP1) antibodies (>40
U/mL for IgG and/or IgM) are diagnostic criterion for APS. Lesser levels of beta-2 GP1 antibodies and
antibodies of the IgA isotype may occur in patients with clinical signs of antiphospholipid syndrome
(APS), but the results are not considered diagnostic. Beta-2 GP1 antibodies must be detected on 2 or
more occasions at least 12 weeks apart to fulfill the laboratory diagnostic criteria for APS. Detection of
beta-2 GP1 antibodies is not affected by anticoagulant treatment.
Reference Values:
<15.0 U/mL (negative)
15.0-39.9 U/mL (weakly positive)
40.0-79.9 U/mL (positive)
> or =80.0 U/mL (strongly positive)
Results are expressed in arbitrary units and apply to IgG and IgM values.
Reference values apply to all ages.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 275
GB2GP Beta-2 Glycoprotein 1 Antibodies, IgG, Serum
86182 Clinical Information: Beta-2 glycoprotein 1 (beta-2 GP1, also called apolipoprotein H) is a
326-amino acid polypeptide synthesized by hepatocytes, endothelial cells, and trophoblast cells. It
contains 5 homologous domains of approximately 60 amino acids each.(1,2) Domain 5, located at the C
terminus, contains a hydrophobic core surrounded by 14 positively charged amino acid residues that
promote electrostatic interactions with plasma membranes via interactions with negatively charged
phospholipids. Complexes of beta 2 GP1 and phospholipid in vivo reveal epitopes that react with natural
autoantibodies.(3) Plasma from normal individuals contains low concentrations of IgG autoantibodies to
beta-2 GP1 (beta-2 GP1 antibodies) that are of moderate affinity and react with an epitope on the first
domain near the N terminus. Pathologic levels of beta 2 GP1 antibodies occur in patients with
antiphospholipid syndrome (APS). APS is associated with a variety of clinical symptoms notably
thrombosis, pregnancy complications, unexplained cutaneous circulatory disturbances (livido reticularis
or pyoderma gangrenosum), thrombocytopenia or hemolytic anemia, and nonbacterial thrombotic
endocarditis. Beta 2 GP1 antibodies are found with increased frequency in patients with systemic
rheumatic diseases, especially systemic lupus erythematosus. Autoantibodies to beta-2 GP1 are detected
in the clinical laboratory by different types of assays including immunoassays and functional coagulation
assays. Immunoassays for beta-2 GP1 antibodies can be performed using either a composite substrate
comprised of beta-2 GP1 plus anionic phospholipid (eg, cardiolipin or phosphatidylserine), or beta-2 GP1
alone. Antibodies detected by immunoassays that utilize composite substrates are commonly referred to as
phospholipid or cardiolipin antibodies. Antibodies detected using beta-2 GP1 substrate without
phospholipid (so-called direct assays) are referred to simply as "beta-2 GP1 antibodies." Some beta-2 GP1
antibodies are capable of inhibiting clot formation in functional coagulation assays that contain low
concentrations of phospholipid cofactors. Antibodies detected by functional coagulation assays are
commonly referred to as lupus anticoagulants. The diagnosis of APS requires at least 1 clinical criteria
and 1 laboratory criteria be met.(5) The clinical criteria include vascular thrombosis (arterial or venous in
any organ or tissue) and pregnancy morbidity (unexplained fetal death, premature birth, severe
preeclampsia, or placental insufficiency). Other clinical manifestations, including heart valve disease,
livedo reticularis, thrombocytopenia, nephropathy, neurological symptoms, are often associated with APS
but are not included in the diagnostic criteria. The laboratory criteria for diagnosis of APS are the
presence of lupus anticoagulant, the presence of IgG and/or IgM anticardiolipin antibody (>40 GPL,
>MPL or >99th percentile), and/or the presence of IgG and/or IgM beta GP1 antibody (>99th percentile).
All antibodies must be demonstrated on 2 or more occasions separated by at least 12 weeks. Direct assays
for beta-2 GP1 antibodies have been reported to be somewhat more specific (but less sensitive) for disease
diagnosis in patients with APS.(4) Anticardiolipin and beta-2 GP1 antibodies of the IgA isotype are not
part of the laboratory criteria for APS due to lack of specificity.
Interpretation: Strongly positive results for beta 2 glycoprotein 1 (beta 2 GP1) antibodies (>40 U/mL
for IgG and/or IgM) are diagnostic criterion for antiphospholipid syndrome (APS). Lesser levels of IgG
and IgM beta 2 GP1 antibodies and antibodies of the IgA isotype may occur in patients with clinical signs
of APS, but the results are not considered diagnostic. Beta 2 GP1 antibodies must be detected on 2 or
more occasions at least 12 weeks apart to fulfill the laboratory diagnostic criteria for APS. Detection of
beta 2 GP1 antibodies is not affected by anticoagulant treatment.
Reference Values:
<15.0 U/mL (negative)
15.0-39.9 U/mL (weakly positive)
40.0-79.9 U/mL (positive)
> or =80.0 U/mL (strongly positive)
Results are expressed in arbitrary units.
Reference values apply to all ages.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 276
sequence of human plasma beta 2 glycoprotein 1. Proc Natl Acad Sci USA 1984;81:3640-3644 3. Kra-Oz
Z, Lorber M, Shoenfeld Y, Scharff Y: Inhibitor(s) of natural anti-cardiolipin autoantibodies. Clin Exp
Immunol 1993;93:265-268 4. Audrain Ma, El-Kouri D, Hamidou MA, et al: Value of autoantibodies to
beta(2)-glycoprotein 1 in the diagnosis of antiphospholipid syndrome. Rheumatology (Oxford)
2002;41:550-553 5. Wong RCW, Flavaloro EJ, Adelstein S, et al: Consensus guidelines on anti-beta 2
glycoprotein I testing and reporting. Pathology 2008 Jan;40(1):58-63
Interpretation: Strongly positive results for beta-2 glycoprotein 1 (beta-2 GPI) antibodies (>40
U/mL for IgG and/or IgM) are diagnostic criterion for antiphospholipid syndrome (APS). Lesser levels
of beta-2 GP1 antibodies and antibodies of the IgA isotype may occur in patients with clinical signs of
APS, but the results are not considered diagnostic. Beta-2 GP1 antibodies must be detected on 2 or more
occasions at least 12 weeks apart to fulfill the laboratory diagnostic criteria for APS. Detection of beta-2
GP1 antibodies is not affected by anticoagulant treatment.
Reference Values:
<15.0 U/mL (negative)
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 277
15.0-39.9 U/mL (weakly positive)
40.0-79.9 U/mL (positive)
> or =80.0 U/mL (strongly positive)
Results are expressed in arbitrary units.
Reference values apply to all ages.
Useful For: Detection of spinal fluid in body fluids, such as ear or nasal fluid
Interpretation: The cerebrospinal fluid (CSF) variant of transferrin is identified by its unique
electrophoretic migration. If beta-1 and beta-2 transferrin are detected in drainage fluids, the specimen is
presumed to be contaminated with CSF. The presence of beta-2 transferrin band is detectable with as little
as 2.5% spinal fluid contamination of body fluids.
Reference Values:
Negative, no beta-2 transferrin (spinal fluid) detected
Useful For: Evaluation of central nervous system inflammation and B-cell proliferative diseases
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 278
Interpretation: Elevations of cerebrospinal fluid beta-2-microgobulin levels may be seen in a
number of diseases including malignancies, autoimmune disease, and neurological disorders.
Reference Values:
0.70-1.80 mcg/mL
Useful For: Prognosis assessment of multiple myeloma Evaluation of renal tubular disorders
Interpretation: Serum beta-2-microglobulin (beta-2-M) <4 mcg/mL is a good prognostic factor in
patients with multiple myeloma. In a study of pretreatment serum beta-2-M levels in 100 patients with
myeloma it was reported that the median survival of patients with values >4 mcg/mL was 12 months,
whereas median survival for patients with values <4 mcg/mL was 43 months.
Reference Values:
1.21-2.70 mcg/mL
Clinical References: 1. Hubin E, Van Nuland NA, Broersen K, Pauwels K: Transient dynamics of
Abeta contribute to toxicity in Alzheimer's disease. Cell Mol Life Sci 2014 Sep;71(18):3507-3521 2.
Bloom GS: Amyloid-beta and tau: the trigger and bullet in Alzheimer disease pathogenesis. JAMA
Neurol 2014 Apr;71(4):505-508 3. Skaper SD: Alzheimer's disease and amyloid: culprit or coincidence?
Int Rev Neurobiol 2012;102:277-316
Useful For: Distinguishing desmoid-type fibromatosis from other soft tissue tumors, when pathological
examination is insufficient for diagnosis
Interpretation: Beta-catenin mutations are detected using PCR and pyrosequencing methods. The
mutant allele frequencies (%) are used to determine beta-catenin mutation status. Results are reported as
positive, negative, or failed. A beta-catenin mutation-positive result supports a diagnosis of desmoid-type
fibromatosis, but a negative result does not necessarily rule out a diagnosis of desmoid-type fibromatosis.
Reference Values:
An interpretative report will be provided.
Clinical References: 1. Lazar AJ, Tuvin D, Hajibashi S, et al: Specific mutations in the beta-catenin
gene (CTNNB1) correlate with local recurrence in sporadic desmoid tumors. Am J Pathol
2008;173:1518-1527 2. Amary MF, Pauwels P, Meulemans E, et al: Detection of beta-catenin mutations
in paraffin-embedded sporadic desmoid-type fibromatosis by mutation-specific restriction enzyme
digestion (MSRED): an ancillary diagnostic tool. Am J Surg Pathol 2007;31:1299-1309 3. Domont J,
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 280
Salas S, Lacroix L, et al: High frequency of beta-catenin heterozygous mutations in extra-abdominal
fibromatosis: a potential molecular tool for disease management. Br J Cancer 2010;102:1032-1036
Useful For: Identification of aberrant nuclear staining pattern observed in some tumors
Interpretation: This test includes only technical performance of the stain (no pathologist
interpretation is performed). If diagnostic consultation by a pathologist is required, order 70012 /
Pathology Consultation. The positive and negative controls are verified as showing appropriate
immunoreactivity. If a control tissue is not included on the slide, a scanned image of the relevant quality
control tissue is available upon request; contact 855-516-8404. Interpretation of this test should be
performed in the context of the patient's clinical history and other diagnostic tests by a qualified
pathologist.
Clinical References: 1. Klymkowsky MW: Beta-catenin and its regulatory network. Hum Pathol
2005 Mar;36(3):225-227 2. Bell DA: Origins and molecular pathology of ovarian cancer. Mod Pathol
2005 Feb;18(Suppl 2):S19-32 3. Smith ME, Pignatelli M: The molecular histology of neoplasia: the role
of the cadherin/catenin complex. Histopathology 1997 Aug;31(2):107-111
Useful For: An aid in monitoring antiresorptive therapies (eg, bisphosphonates and hormone
replacement therapy) in postmenopausal women treated for osteoporosis and individuals diagnosed with
osteopenia An adjunct in the diagnosis of medical conditions associated with increased bone turnover
Reference Values:
Males
<18 years: not established
18-30 years: 120-946 pg/mL
31-50 years: 93-630 pg/mL
51-70 years: 35-836 pg/mL
>70 years: not established
Females
<18 years: not established
Premenopausal: 25-573 pg/mL
Postmenopausal: 104-1,008 pg/mL
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 282
typically characterized by progressive neurologic degeneration, ataxia, and angiokeratomas. The
incidence of the juvenile/adult form is greater in individuals with Japanese ancestry. Patients with
mucolipidosis II/III (I-cell disease) may also demonstrate deficiency of beta-galactosidase in leukocytes,
in addition to deficiency of other hydrolases. I-cell disease is an autosomal recessive lysosomal storage
disorder resulting in impaired transport and phosphorylation of newly synthesized lysosomal proteins to
the lysosome due to deficiency of N-acetylglucosamine 1-phosphotransferase (GlcNAc). Characteristic
clinical features include short stature, skeletal and cardiac abnormalities, and developmental delay.
Measurement of beta-galactosidase activity is not the preferred diagnostic test for I-cell disease but may
be included in the testing strategy. A diagnostic workup in an individual with GM1 gangliosidosis,
Morquio B, or galactosialidosis typically demonstrates decreased beta-galactosidase enzyme activity in
leukocytes or fibroblasts; however, additional testing and consideration of the patients clinical
findings are necessary to differentiate between these conditions. Individuals with GM1 gangliosidosis can
have characteristic abnormalities on urine oligosaccharides and have elevated keratan sulfate in urine
(however, to a lesser degree than seen in patients with Morquio B). Individuals with Morquio B can have
increased keratan sulfate in urine. Molecular sequence analysis of the GLB1 gene allows for detection of
the disease-causing mutations in affected patients with GM1 gangliosidosis or Morquio B. Individuals
with galactosialidosis also demonstrate abnormalities on urine oligosaccharides as well as decreased
neuraminidase activity in fibroblasts. Sequencing of the CTSA gene allows for detection of
disease-causing mutations in patients with galactosialidosis.
Useful For: Diagnosis of GM1 gangliosidosis, Morquio B disease, and galactosialidosis in whole
blood specimens
Interpretation: Results below 5.0 nmol/hour/mL in properly submitted specimens are consistent
with beta-galactosidase deficiency (GM1 gangliosidosis, Morquio B disease, or galactosialidosis).
Further differentiation between GM1, Morquio B, and galactosialidosis is dependent on the patient's
clinical findings and results of additional biochemical testing. Normal results (> or =5.0 nmol/h/mL) are
not consistent with beta-galactosidase deficiency.
Reference Values:
> or =5.0 nmol/hour/mL
An interpretive report will be provided.
Useful For: Diagnosis of beta-galactosidase deficiency (GM1 gangliosidosis, Morquio B disease and
galactosialidosis) in blood spot specimens
Interpretation: Properly submitted specimens with results less than 5.0 nmol/h/mL are consistent with
beta-galactosidase deficiency (GM1 gangliosidosis, Morquio B disease, or galactosialidosis). Further
differentiation between GM1, Morquio B, and galactosialidosis is dependent on the patient's clinical
findings and results of additional biochemical testing. Normal results (> or =5.0 nmol/hour/mL) are not
consistent with beta-galactosidase deficiency.
Reference Values:
> or =5.0 nmol/hour/mL
An interpretive report will be provided.
Reference Values:
> or =7.11 nmol/min/mg protein
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characteristic of galactosialidosis.
Reference Values:
> or =1.56 nmol/min/mg
Reference Values:
> or =4.85 nmol/min/mg protein
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Vogelstein, et al. New York, NY: McGraw-Hill; 2014. Available from
http://ommbid.mhmedical.com/content.aspx?bookid=971&Sectionid=62643884. Accessed March 17,
2015 3. Pastores GM, Hughes DA. Gaucher Disease. 2007 In: GeneReviews. Edited by RA Pagon, MP
Adam, HH Ardinger, et al. Seattle WA: University of Washington, Seattle;1993-2015. Available from:
http://www.ncbi.nlm.nih.gov/books/NBK1269/ Accessed 3/17/2015 4. Weinreb NJ, Andersson HC,
Banikazemi M, et al: Prevalence of type 1 Gaucher disease in the United States. Arch Intern Med 2008
Feb 11;168(3):326-327
Clinical References: 1. Martins AM, Valadares ER, Porta G, et al: Recommendations on diagnosis,
treatment, and monitoring for Gaucher disease. J Pediatr 2009 Oct;155(4 Suppl):S10-S18 2. Grabowski
GA, Petsko GA, Kolodny EH: Chapter 146: Gaucher Disease. In Scrivers The Online Metabolic and
Molecular Basis of Inherited Disease. Edited by D Valle, AL Beaudet, B Vogelstein, et al. New York,
McGraw-Hill Medical Division. Accessed 3/17/2015. Available at www.ommbid.com 3. Pastores GM,
Hughes DA: Gaucher disease. In GeneReviews. Edited by RA Pagon, MP Adam, HH Ardinger, et al.
University of Washington. 2000 Jul 27 (Updated 2015 Feb 26). Accessed 3/17/2015. Available at
www.ncbi.nlm.nih.gov/books/NBK1269/ 4. Weinreb NJ, Andersson HC, Banikazemi M, et al: Prevalence
of type 1 Gaucher disease in the United States. Arch Intern Med 2008;168:326-328
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BGLR Beta-Glucuronidase, Fibroblasts
8006 Clinical Information: Mucopolysaccharidosis VII (MPS VII, Sly syndrome) is an autosomal
recessive lysosomal storage disorder caused by the deficiency of beta-glucuronidase. The
mucopolysaccharidoses are a group of disorders caused by the deficiency of any of the enzymes
involved in the stepwise degradation of glycosaminoglycans (GAG). Accumulation of GAGs (also
called mucopolysaccharides) in lysosomes interferes with normal functioning of cells, tissues, and
organs. MPS VII is caused by a reduced or absent activity of the beta-glucuronidase enzyme and gives
rise to the physical manifestations of the disease. Clinical features and severity of symptoms of MPS
VII are widely variable ranging from severe lethal hydrops fetalis to more mild forms, which generally
present at a later onset with a milder clinical presentation. In general, symptoms may include skeletal
anomalies, coarse facies, hepatomegaly, neurological issues, and mental retardation. Treatment options
may include bone marrow transplantation. Sly syndrome is 1 of the least common
mucopolysaccharidoses with an incidence of 1 in 250,000 live births. A diagnostic workup in an
individual with MPS VII typically demonstrates elevated levels of urinary GAGs and increased amounts
of dermatan sulfate, heparan sulfate, and chondroitin 6-sulfate detected on thin-layer chromatography.
Reduced or absent activity of beta-glucuronidase in fibroblasts can confirm a diagnosis of MPS VII;
however, enzymatic testing is not reliable to detect carriers. Molecular sequence analysis of the GUSB
gene allows for detection of the disease-causing mutation in affected patients and subsequent carrier
detection in relatives. Currently, no clear genotype-phenotype correlations have been established.
Reference Values:
> or =2.33 nmol/min/mg protein
Clinical References: Neufeld EF, Muenzer J. Neufeld E.F., Muenzer J Neufeld, Elizabeth F., and
Joseph Muenzer.The Mucopolysaccharidoses. Edited by D Valle, AL Beaudet, B Vogelstein,et al:New
York, NY: McGraw-Hill; 2014. Accessed April 22, 2015. Available at
http://ommbid.mhmedical.com/content.aspx?bookid=971&Sectionid=62642135
Useful For: Monitoring patients for retained products of conception An aid in the diagnosis of
gestational trophoblastic disease (GTD), testicular tumors, ovarian germ cell tumors, teratomas, and,
rarely, other human chorionic gonadotropin (hCG)-secreting tumors Serial measurement of hCG
following treatment to: -Monitor therapeutic response in GTD or in hCG-secreting tumors -Detect
persistent or recurrent GTD or hCG-secreting tumors
Reference Values:
Children(1,2)
Males
Birth-3 months: < or =50 IU/L*
>3 months-<18 years: <1.4 IU/L
Females
Birth-3 months: < or =50 IU/L*
>3 months-<18 years: <1.0 IU/L
*hCG, produced in the placenta, partially passes the placental barrier. Newborn serum beta-hCG
concentrations are approximately 1/400th of the corresponding maternal serum concentrations, resulting
in neonate beta-hCG levels of 10-50 IU/L at birth. Clearance half-life is approximately 2-3 days.
Therefore, by 3 months of age, levels comparable to adults should be reached.
Clinical References: 1. Cole LA, Khanlian SA, Muller CY: Detection of perimenopause or
postmenopause human chorionic gonadotropin: an unnecessary source of alarm. Am J Obstet Gynecol
2008;198:275.e1-275.e7 2. Schneider DT, Calaminus G, Gobel U: Diagnostic value of alpha
1-fetoprotein and beta-human chorionic gonadotropin in infancy and childhood. Pediatr Hematol Oncol
2001;18(1):11-26 3. Cole LA, Butler S: Detection of hCG in trophoblastic disease. The USA hCG
reference service experience. J Reprod Med 2002;40(6):433-444 4. von Eyben FE: Laboratory markers
and germ cell tumors. Crit Rev Clin Lab Sci 2003;40(4):377-427 5. Sturgeon CM, Duffy MJ, Stenman
UH: National Academy of Clinical Biochemistry laboratory medicine practice guidelines for use of
tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers. Clin Chem 2008;
54(12):e11-79
Useful For: As an aid in the diagnosis of brain metastases of testicular cancer or extragonadal
intracerebral germ cell tumors
Interpretation: Elevated levels of human chorionic gonadotropin in spinal fluid indicate the
probable presence of central nervous system metastases or recurrence of tumor in patients with germ
cell tumors, including patients with testicular cancer or choriocarcinoma.
Reference Values:
<1.0 IU/L
Clinical References: 1. Tian C, Shi Q, Xiao G, et al: CSF and serum hCG in patients without
gestational and neoplastic hCG-secretion. Scand J Clin Lab Invest Suppl 2011;71:264-268 2. Tian C,
Shi Q, Pu C, et al: Re-evaluation of the significance of cerebrospinal fluid human chorionic
gonadotropin in detecting intracranial ectopic germinoas. J Clin Neurosci 2011;18:223-226 3.
Gonzalez-Sanchez V, Moreno-Perez O, Pellicer PS, et al: Validation of the human chorionic
gonadotropin immunoassay in cerebrospinal fluid for the diagnostic work-up of neurohypophyseal
germinomas. Ann Clin Biochem 2011;48: 433-437
Useful For: Monitoring therapy for diabetic ketoacidosis Investigating the differential diagnosis of any
patient presenting to the emergency room with hypoglycemia, acidosis, suspected alcohol ingestion, or an
unexplained increase in the anion gap In pediatric patients, the presence or absence of ketonemia/uria is
an essential component in the differential diagnosis of inborn errors of metabolism Serum
beta-hydroxybutyrate is a key parameter monitored during controlled 24-hour fasts
Interpretation: The beta-hydroxybutyrate (BHB)/acetoacetate ratio is typically between 3:1 and 7:1 in
severe ketotic states. Serum BHB increases in response to fasting, but should not exceed 0.4 mmol/L
following an overnight fast (up to 12 hours). In pediatric patients, a hypo- or hyper-ketotic state (with or
without hypoglycemia) may suggest specific groups of metabolic disorders.
Reference Values:
<0.4 mmol/L
BLACT Beta-Lactamase
8118 Clinical Information: Various bacteria produce a class of enzymes called beta-lactamases, which
may be mediated by genes on plasmids or chromosomes. Production of beta-lactamase may be
constitutive or induced by exposure to antimicrobials. Beta-lactamases hydrolyze (and thereby inactivate)
the beta-lactam rings of a variety of susceptible penicillins and cephalosporins. Beta-lactamases are
classified by their preferred antimicrobial substrate and the effect of various inhibitors (such as clavulanic
acid) on them. Some antimicrobials, such as cefazolin and cloxacillin are resistant to such hydrolysis (at
least for staphylococcal beta-lactamases). Beta-lactamase producing strains of the following are resistant
to many types of penicillin: Staphylococcus species, Hemophilus influenzae, Neisseria gonorrhoeae,
Bacteroides species, Enterococcus species, and Moraxella catarrhalis. The above organisms, when
isolated from critical specimens such as blood or spinal fluid, should always be tested for beta-lactamase
production. Addition of a beta-lactamase inhibitor to a beta-lactam (such as sulbactam plus ampicillin)
restores the activity of the antimicrobials.
Clinical References: Livermore DM, Williams JD: Beta-lactams: mode of action and mechanisms
of bacterial resistance. In Antibiotics in Laboratory Medicine. Fourth edition. Edited by V Lorian.
Baltimore, MD, Williams and Wilkins, 1996, pp 502-578
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immune response to allergens that may be associated with allergic disease. The allergens chosen for
testing often depend upon the age of the patient, history of allergen exposure, season of the year, and
clinical manifestations. In individuals predisposed to develop allergic disease, the sequence of
sensitization and clinical manifestations proceed as follows: eczema and respiratory disease (rhinitis and
bronchospasm) in infants and children less than 5 years due to food sensitivity (milk, egg, soy, and wheat
proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: The bicarbonate content of serum or plasma is a significant indicator of electrolyte
dispersion and anion deficit. Together with pH determination, bicarbonate measurements are used in the
diagnosis and treatment of numerous potentially serious disorders associated with acid-base imbalance
in the respiratory and metabolic systems. Some of these conditions are diarrhea, renal tubular acidosis,
carbonic anhydrase inhibitors, hyperkalemic acidosis, renal failure, and ketoacidosis.
Reference Values:
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Males
1-2 years: 17-25 mmol/L
3 years: 18-26 mmol/L
4-5 years: 19-27 mmol/L
6-7 years: 20-28 mmol/L
8-17 years: 21-29 mmol/L
> or =18 years: 22-29 mmol/L
Females
1-3 years: 18-25 mmol/L
4-5 years: 19-26 mmol/L
6-7 years: 20-27 mmol/L
8-9 years: 21-28 mmol/L
> or =10 years: 22-29 mmol/L
Reference values have not been established for patients that are <12 months of age.
Clinical References: Tietz Textbook of Clinical Chemistry, Edited by Burtis and Ashwood.
Philadelphia, PA, WB Saunders Company, 1994.
Useful For: Biomarker for peroxisomal biogenesis disorders and single enzyme defects of bile acid
synthesis including D-bifunctional protein deficiency and alpha methyl CoA racemaces Monitoring
patients receiving bile acid therapy such as cholic acid for liver disease due to peroxisomal biogenesis
disorders or single enzyme defects in bile acid synthesis
Interpretation: Increases in serum C27 bile acids are seen in patients with peroxisomal biogenesis
disorders or single enzyme defects of bile acid synthesis such as D-bifunctional protein deficiency and
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alpha methyl CoA racemaces. Total bile acids are metabolized in the liver and can serve as a marker for
normal liver function.
Reference Values:
Analyte Normal (nmol/mL)
Dihydroxycholestanoic Acid < or =0.10
Trihydroxycholestanoic Acid < or =1.30
Total Cholic Acid < or =5.00
Total Chenodeoxycholic Acid < or =6.00
Total Ursodeoxycholic Acid < or =2.00
Total Bile Acids < or =19.00
Clinical References: 1. Johnson DW, Brink HJ, Schuit RC, et al: Rapid and quantitative analysis
of unconjugated C27 bile acids in plasma and blood samples by tandem mass spectrometry. Journ Lipid
Res 2001;42:9-16 2. Bootsma AH, Overmars H, Van Rooiji A, et al: Rapid analysis of conjugated bile
acids in plasma using electrospray tandem mass spectrometry: Application for selective screening of
peroxisomal disorders. J Inher Metab Dis 1999;22:307-310 3. Ferdinandusse S, Jimenez-Sanchez G,
Koster J, et al: A novel bile acid biosynthesis defect due to a deficiency of peroxisomal ABCD3. Hum
Mol Genet 2015;24:361-370 4. Heubi J, Setchell KDR, Bove KE: Inborn Errors of Bile Acid
Metabolism. Sem Liver Dis 2007;27:282-294
Useful For: An aid to evaluate patients suspected of having irritable bowel syndrome-diarrhea
(IBS-D) symptoms due to bile acid malabsorption
Interpretation: Elevated total fecal bile acid is consistent with the diagnosis of bile acid
malabsorption. Pharmacological treatment with bile acid sequestrants has been shown to improve
symptoms in some patients.
Reference Values:
Sum of cholic acid and chenodeoxycholic acid < or =3.7%
Total bile acids < or =2,619 mcmoles/48 hours
Clinical References: 1. Wedlake L, A'Hern R, Russell D, et al: Systematic review: the prevalence
of idiopathic bile acid malabsorption as diagnosed by SeHCAT scanning in patients with
diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther 2009;30:707-717 2. Shin A,
Camilleri M, Vijayvargiya P, et al: Bowel functions, fecal unconjugated primary and secondary bile
acids, and colonic transit in patients with irritable bowel syndrome. Clin Gastroenterol Hepatol 2013
Oct;11(10):1270-1275 3. Longstreth GF, Thompson WG, Chey WD, et al: Functional Bowel Disorders.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 295
Gastroenterology 2006;130:1480-1491 4. Camilleri M, McKinzie S, Busciglio I, et al: Prospective study
of motor, sensory, psychologic, and autonomic functions in patients with irritable bowel syndrome. Clin
Gastroenterol Hepatol 2008;6:772-781 5. Vijayvargiya P, Camilleri M, Shin A, Saenger A: Methods for
diagnosis of bile acid malabsorption in clinical practice. Clin Gastroenterol Hepatol 2013
Oct;11(10):1232-1239
Useful For: Measurement of tauro- and glycol-conjugated and unconjugated bile acid constituents in
serum Monitoring patients receiving bile acid therapy, such as cholic acid, deoxycholic acid, or
ursodeoxycholic acid Aiding in the evaluation of liver function; evaluation of liver function changes
before the formation of more advanced clinical signs of illness such as icterus Determining hepatic
dysfunction as a result of chemical and environmental injury Indication of hepatic histological
improvement in chronic hepatitis C patients responding to interferon treatment Indication of intrahepatic
cholestasis of pregnancy
Interpretation: Total bile acids are metabolized in the liver and can serve as a marker for normal liver
function. Increases in serum bile acids are seen in patients with acute hepatitis, chronic hepatitis, liver
sclerosis, liver cancer, and intrahepatic cholestasis of pregnancy.
Reference Values:
Analyte Normal (nmol/mL)
Clinical References: 1. Tribe RM, Dann AT, Kenyon AP, et al: Longitudinal profiles of 15 serum
bile acids in patients with intrahepatic cholestasis of pregnancy. Am J Gastroenterol 2010
Mar;105(3):585-595 2. Marschall HU: Management of intrahepatic cholestasis of pregnancy. Expert Rev
Gastroenterol Hepatol 2015 Oct;9(10):1273-1279 3. Ducroq DH, Morton MS, Shadi N, et al: Analysis of
serum bile acids by isotope dilution-mass spectrometry to assess the performance of routine total bile acid
methods. Ann Clin Biochem 2010 Nov;47(Pt 6):535-540
Useful For: An aid in the evaluation of liver function Evaluation of liver function changes before the
formation of more advanced clinical signs of illness such as icterus An aid in the determination of
hepatic dysfunction as a result of chemical and environmental injury An indicator of hepatic histological
improvement in chronic hepatitis C patients responding to interferon treatment An indicator for
intrahepatic cholestasis of pregnancy
Interpretation: Total bile acids are metabolized in the liver and can serve as a marker for normal
liver function. Increases in serum bile acids are seen in patients with acute hepatitis, chronic hepatitis,
liver sclerosis, and liver cancer.
Reference Values:
< or =10 mcmol/L
Clinical References: 1. Sawkat Anwer M, Meyer DJ: Bile Acids in the Diagnosis, Pathology, and
Therapy of Hepatobiliary Diseases. Vet Clin North Am Small Anim Pract 1995 March;25(2):503-517 2.
Javitt NB: Diagnostic Value of Serum Bile Acids. Clin Gastroenterol 1977;6:219-226 3. Osuga T,
Mitamura K, Mashige F, et al: Evaluation of Fluorimetrically Estimated Serum Bile Acid in Liver
Disease. Clin Chim Acta 1977;75:81-90 4. Shima T, Tada H Morimoto M, et al: Serum Total Bile Acid
Level as a Sensitive Indicator of Hepatic Histological Improvement in Chronic Hepatitis C Patients
Responding to Interferon Treatment. J Gastroenterol Hepatol 2000 March;15(30:294-299 4. Lebovics E,
Seif F, Kim D, et al: Pruritus in Chronic Hepatitis C: Association with High Serum Bile Acids,
Advanced Pathology, and Bile Duct Abnormalities. Dig Dis Sci 1997 May;42(5):1094-1099 5. Korman
MG, Hofmann AF, Summerskill WHJ: Assessment of Activity in Chronic Active Liver Disease. Serum
Bile Acids Compared with Conventional Tests and Histology. NEJM 1974 June 20;290:1399-1402
Useful For: Assessing bile duct brushing or hepatobiliary brushing specimens for malignancy
Interpretation: An interpretive report will be provided.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Barr Fritcher EG, Kipp BR, Voss JS, et al: The Development of a Tailored
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Pancreatobiliary Fluorescence in situ Hybridization (FISH) Assay to Improve Detection of Malignancy
in Pancreatobiliary Brushings. J Mol Diagn 2013;15(6):909 2. Barr Fritcher EG, Kipp BR, Halling KC,
et al: A multivariable model using advanced cytologic methods for the evaluation of indeterminate
pancreatobiliary strictures. Gastroenterology 2009;136(7):2180-2186
Useful For: Assessing bile duct brushing or hepatobiliary brushing specimens for malignancy
Interpretation: An interpretive report will be provided.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Barr Fritcher EG, Kipp BR, Voss JS, et al: The Development of a Tailored
Pancreatobiliary Fluorescence in situ Hybridization (FISH) Assay to Improve Detection of Malignancy in
Pancreatobiliary Brushings. J Mol Diagn 2013;15(6):909 2. Barr Fritcher EG, Kipp BR, Halling KC, et al:
A multivariable model using advanced cytologic methods for the evaluation of indeterminate
pancreatobiliary strictures. Gastroenterology 2009;136(7):2180-2186
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and the clinical setting.
Reference Values:
> or =12 months: 0.0-0.3 mg/dL
Reference values have not been established for patients who are <12 months of age.
Useful For: Evaluation of Rh disease, ie, hemolytic disease of the fetus Monitoring disease
progression to assess need for fetal transfusion
Interpretation: The reference range for bilirubin in amniotic fluid is related to the gestational age of
the fetus. Refer to either the Queenan Curve (gestational age <27 weeks) or the Liley Chart (gestational
age >27 weeks) listed under Interpretation of Amniotic Fluid Bilirubin Results (Delta OD 450) in
Special Instructions.
Reference Values:
Interpretation of fetal risk is dependent upon gestational age.
Refer to either the Queenan Curve (gestational age <27 weeks) or the Liley Chart (gestational age >27
weeks) listed under Interpretation of Amniotic Fluid Bilirubin Results (Delta OD 450) in Special
Instructions.
Clinical References: 1. Scott F, Chan FY: Assessment of the clinical usefulness of the 'Queenan'
chart versus the 'Liley' chart in predicting severity of rhesus iso-immunization. Prenat Diagn
1998;18:1143-1148 2. Liley AW: Liquor amnii analysis in the management of the pregnancy
complicated by rhesus sensitization. Am J Obstet Gynecol 1961;82:1359-1370
Useful For: May aid in the distinction between a transudative and an exudative body fluid, when
used in conjunction with other testing including serum bilirubin analysis, body fluid; serum protein
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ratio, body fluids; serum lactate dehydrogenase ratio, and serum lactate dehydrogenase
Interpretation: Elevated body fluid bilirubin is suggestive of an exudative fluid. This testing should be
performed in conjunction with other testing including serum bilirubin analysis, body fluid:serum protein
ratio, body fluids:serum lactate dehydrogenase ratio, and serum lactate dehydrogenase.
Reference Values:
Not applicable
The reference range has not been established for bilirubin in body fluids. The test result should be
integrated into the clinical context for interpretation.
Clinical References: 1. Elis A, Meisel S, Tishler T, et al: Ascitic fluid to serum bilirubin
concentration ratio for the classification of transudates or exudates. Am J Gastroenterol 1998
Mar;93(3):401-403 2. Runyon BA: Ascitic fluid bilirubin concentration as a key to choleperitoneum. J
Clin Gastroenterol 1987 Oct;9(5):543-545 3. Darwin P, Goldberg E, Uradomo L: Jackson Pratt drain
fluid-to-serum bilirubin concentration ratio for the diagnosis of bile leaks. Gastrointest Endosc 2010
Jan;71(1):99-104 Epub 2009, Nov 27 4. Burgess LJ: Biochemical analysis of pleural, peritoneal and
pericardial effusions. Clin Chim Acta 2004 May;343(1-2):61-84 5. Clinical and Laboratory Standards
Institute: Analysis of Body Fluids in Clinical Chemistry; Approved Guideline. Clinical and Laboratory
Standards Institute, Wayne, PA, 2007, CLSI document C49-A (ISBN 1-56238-638-7)
Useful For: Assessing liver function Evaluating a wide range of diseases affecting the production,
uptake, storage, metabolism, or excretion of bilirubin Monitoring the efficacy of neonatal phototherapy
Interpretation: The level of bilirubinemia that results in kernicterus in a given infant is unknown. In
preterm infants, the risk of a handicap increases by 30% for each 2.9 mg/dL increase of maximal total
bilirubin concentration. While central nervous system damage is rare when total serum bilirubin (TSB) is
<20 mg/dL, premature infants may be affected at lower levels. The decision to institute therapy is based
on a number of factors including TSB, age, clinical history, physical examination, and coexisting
conditions. Phototherapy typically is discontinued when TSB level reaches 14 to 15 mg/dL. Physiologic
jaundice should resolve in 5 to 10 days in full-term infants and by 14 days in preterm infants. When any
portion of the biliary tree becomes blocked, bilirubin levels will increase.
Reference Values:
DIRECT
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> or =12 months: 0.0-0.3 mg/dL
Reference values have not been established for patients who are <12 months of age.
TOTAL
<1 month: not established
1 month-17 years: < or =1.0 mg/dL
> or =18 years: < or =1.2 mg/dL
Useful For: Assessing liver function Evaluating a wide range of diseases affecting the production,
uptake, storage, metabolism, or excretion of bilirubin Monitoring the efficacy of neonatal phototherapy
Interpretation: The level of bilirubinemia that results in kernicterus in a given infant is unknown,
While central nervous system damage is rare when total serum bilirubin (TSB) is <20 mg/dL, premature
infants may be affected at lower levels. The decision to institute therapy is based on a number of factors
including TSB, age, clinical history, physical examination and coexisting conditions. Phototherapy
typically is discontinued when TSB level reaches 14 to 15 mg/dL. Physiologic jaundice should resolve
in 5 to 10 days in full-term infants and by 14 days in preterm infants. In preterm infants, the risk of a
handicap increases by 30% for each 2.9 mg/dL increase of maximal total bilirubin concentration. When
any portion of the biliary tree becomes blocked, bilirubin levels will increase.
Reference Values:
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<1 month: not established
1 month-17 years: < or =1.0 mg/dL
> or =18 years: < or =1.2 mg/dL
Reference Values:
Negative
If positive, results reported as trace or positive.
Clinical References: Brunzel, NA, Fundamentals of Urine and Body Fluid Analysis, W.B. Saunders
Company, Philadelphia, 1994.
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biochemical and molecular testing. Biotinidase deficiency is inherited in an autosomal recessive manner,
caused by mutations in the biotinidase gene (BTD). The carrier frequency for biotinidase deficiency in the
general population is about 1:120. Several common mutations in the BTD gene have been identified,
accounting for about 60% of affected individuals. Sequencing of the entire BTD gene detects other, less
common, disease-causing mutations. While genotype-phenotype correlations are not well established, it
appears that certain mutations are associated with profound biotinidase deficiency, while others are
associated with partial deficiency. The recommended first-tier test to screen for biotinidase deficiency is a
biochemical test that measures biotinidase enzyme activity, either newborn screening or BIOTS /
Biotinidase, Serum. Molecular tests form the basis of confirmatory or carrier testing. Individuals with
decreased enzyme activity are more likely to have 2 identifiable mutations in the BTD gene by molecular
genetic testing.
Useful For: Second-tier test for confirming biotinidase deficiency (indicated by biochemical testing
or newborn screening) Carrier testing of individuals with a family history of biotinidase deficiency, but
disease-causing mutations have not been identified in an affected individual
Interpretation: All detected alterations are evaluated according to American College of Medical
Genetics recommendations.(1) Variants are classified based on known, predicted, or possible
pathogenicity and reported with interpretive comments detailing their potential or known significance.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for
standards of interpretation and reporting of sequence variations: revisions 2007. Genet Med
2008;10(4):294-300 2. Kaye CI, Committee on Genetics, Accurso F, et al: Newborn screening fact
sheets. Pediatrics 2006 Sep;118(3):e934-963 3. Moslinger D, Muhl A, Suormala T, et al: Molecular
characterization and neuropsychological outcome of 21 patients with profound biotinidase deficiency
detected by newborn screening and family studies. Eur J Pediatr 2003 Dec;162 Suppl 1:S46-49 Epub
2003 Nov 20 4. Nyhan WL, Barshop B, Ozand PT: Multiple carboxylase deficiency/biotinidase
deficiency. In Altas of Metabolic Diseases. Second edition. New York, Oxford University Press, 2005
pp 42-48 5. Wolf B, Jensen KP, Barshop B, et al: Biotinidase deficiency: novel mutations and their
biochemical and clinical correlates. Hum Mutat 2005 Apr;25(4):413
Useful For: Preferred test for diagnosing biotinidase deficiency Follow-up testing for certain organic
acidurias
Interpretation: The reference range is 3.5 U/L to 13.8 U/L. Partial deficiencies and carriers may occur
at the low end of the reference range. Values less than 3.5 U/L are occasionally seen in specimens from
unaffected patients.
Reference Values:
3.5-13.8 U/L
Clinical References: 1. Zempleni J, Barshop BA, Cordonier EL, et al: Disorders of Biotin
Metabolism. In The online Metabolic and Molecular Base of Inherited Disease. Edited by D Valle, AL
Beaudet, B Vogelstein, et al: New York, McGraw-Hill; 2014. Accessed August 24, 2015. Available at:
http://ommbid.mhmedical.com/content.aspx?bookid=971&Sectionid=62646613 2. Wolf B: Biotinidase
Deficiency. In GeneReviews. Edited by RA Pagon, MP Adam, HH Ardinger, et al: University of
Washington, Seattle, 1993-2016. Updated 2013 Dec 5. Available at:
www.ncbi.nlm.nih.gov/books/NBK1322/
Pigeon/Dove Serum Negative The gel diffusion method was used to test this
patient's serum for the presence of precipitating antibodies
(IgG) to the antigens indicated. These antibodies are
serological markers for exposure and immunological
sensitization. The clinical significance varies, depending on
the history and symptoms.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 304
is the only gene known to be associated with BHDS. Sequence analysis detects mutations in FLCN in
88% of affected individuals. Recent studies have reported that multi-exonic deletions can account for up
to 5% to 10% of additional mutations.(2, 3) Molecular genetic testing is indicated in all individuals known
to have or suspected of having BHDS, including individuals with one of the following: -Five or more
facial or truncal papules with at least 1 histologically confirmed fibrofolliculoma, with or without a family
history of BHDS -Facial papules histologically confirmed to be angiofibroma in an individual who does
not fit the clinical criteria of tuberous sclerosis complex (TSC) or multiple endocrine neoplasia type 1
(MEN1) -Multiple and bilateral chromophobe, oncocytic, and/or hybrid renal tumors -A single oncocytic,
chromophobe, or oncocytic hybrid renal tumor and a family history of renal cancer with any of these renal
cell tumor family history of renal cancer with any of the above renal cell tumor types -A family history of
autosomal dominant primary spontaneous pneumothorax without a history of smoking or chronic
obstructive pulmonary disease (COPD) In the absence of an increased risk of developing childhood
malignancy, the American Society of Clinical Oncology (ASCO) recommends delaying genetic testing in
at-risk individuals until they reach age 18 years and are able to make informed decisions regarding genetic
testing.
Useful For: Genetic diagnosis of Birt-Hogg-Dube syndrome for clinical management, risk
assessment for related clinical symptoms, and genetic counseling for family members
Interpretation: All detected alterations will be evaluated according to American College of Medical
Genetics and Genomics (ACMG) recommendations.(1) Variants will be classified based on known,
predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or
known significance.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for
standards for interpretation and reporting of sequence variations: Revisions 2007. Genet Med
2008:10(4):294-300 2. Benhammou JN, Vocke CD, Santani A, et al: Identification of intragenic
deletions and duplication in the FLCN gene in Birt-Hogg-Dube syndrome. Genes Chromosomes Cancer
2011;50:466-477 3. Houweling AC, Gijezen LM, Joneker MA, et al: Renal cancer and pneumothorax
risk in Birt-Hogg-Dube syndrome; an analysis of 115 FLCN mutation carriers from 35 BHD families.
Br J Cancer 2011;105:1912-1919 4. Schmidt LS, Nickerson ML, Warren MB, et al: Germline
BHD-mutation spectrum and phenotype analysis of a large cohort of families with Birt-Hogg-Dube
Syndrome. Am J Hum Genet 2005;76:1023-1033
Reference Values:
<1 ng/mL (unexposed)
4-30 ng/mL (therapeutic)
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 305
Clinical References: 1. Baselt R: Disposition of Toxic Drugs and Chemicals In Man. 10th edition.
2014, Biomedical Publications. Seal Beach, CA 2. Heitland P, Koster HD: Biomonitoring of 37 trace
elements in blood samples from inhabitants of northern Germany by ICP-MS. J Trace Elem Med Biol
2006;20(4):253-262 3. Serfontein WJ, Mekel R, Bank S, et al: Bismuth toxicity in man - I. Bismuth blood
and urine levels in patients after administration of a bismuth protein complex (Bicitropeptide). Res
Commun Chem Pathol Pharmacol 1979;26(2):383-390 4. Serfontein WJ, Mekel R: Bismuth toxicity in
man II. Review of bismuth blood and urine levels in patients after administration of therapeutic bismuth
formulations in relation to the problem of bismuth toxicity in man. Res Commun Chem Pathol Pharmacol
1979;26(2):391-411
Reference Values:
Negative
Reference Values:
Negative
Useful For: A prospective and diagnostic marker for the development of nephropathy in renal
transplant recipients
Interpretation: Increasing copy levels of BK virus (BKV) DNA in serial specimens may indicate
possible BKV- associated nephropathy (BKVAN) in kidney transplant patients. Viral loads >10,000
copies/mL in plasma may also indicate a risk for BKVAN. This assay does not cross react with other
polyomaviruses, including JC virus and Simian virus 40 (SV-40).
Reference Values:
None detected
Useful For: A prospective and diagnostic marker for the development of BK virus nephropathy in renal
transplant recipients
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 308
Interpretation: Increasing copy levels of BK virus (BKV) DNA in serial specimens may indicate
possible BKV-associated nephropathy (BKVAN) in kidney transplant patients. Viral loads of >100,000
copies/mL in urine may also indicate a risk for BKVAN. This assay does not cross react with other
polyomaviruses, including JC virus and SV-40.
Reference Values:
None detected
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 309
6 > or =100 Strongly positive Reference values
apply to all ages.
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 310
night sweats. It commonly spreads to the skin, bone, or internal genitalia where suppuration and
granulomas are typical. Occasionally, primary cutaneous lesions after trauma are encountered; however,
this type of infection is uncommon.
Reference Values:
Negative
Reference Values:
Negative
Reference Values:
Negative
Reference Values:
Negative
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Useful For: Detection of the more common potential causes of abnormal bleeding (eg, factor
deficiencies/hemophilia, von Willebrand disease, factor-specific inhibitors) and a simple screen to
evaluate for an inhibitor or severe deficiency of factor XIII (rare).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: The determination of serum blood urea nitrogen currently is the most widely used
screening test for the evaluation of kidney function. The test is frequently requested along with the serum
creatinine test since simultaneous determination of these 2 compounds appears to aid in the differential
diagnosis of prerenal, renal and postrenal hyperuremia.
Interpretation: Serum blood urea nitrogen (BUN) determinations are considerably less sensitive than
BUN clearance (and creatinine clearance) tests, and levels may not be abnormal until the BUN clearance
has diminished to <50%. Clinicians frequently calculate a convenient relationship, the urea
nitrogen/creatinine ratio: serum bun in mg/dL/serum creatinine in mg/dL. For a normal individual on a
normal diet, the reference interval for the ratio ranges between 12 and 20, with most individuals being
between 12 and 16. Significantly lower ratios denote acute tubular necrosis, low protein intake, starvation
or severe liver disease. High ratios with normal creatinine levels may be noted with catabolic states of
tissue breakdown, prerenal azotemia, high protein intake, etc. High ratios associated with high creatinine
concentrations may denote either postrenal obstruction or prerenal azotemia superimposed on renal
disease. Because of the variability of both the BUN and creatinine assays, the ratio is only a rough guide
to the nature of the underlying abnormality. Its magnitude is not tightly regulated in health or disease and
should not be considered an exact quantity.
Reference Values:
Males
1-17 years: 7-20 mg/dL
> or =18 years: 8-24 mg/dL
Reference values have not been established for patients who are <12 months of age.
Females
1-17 years: 7-20 mg/dL
> or =18 years: 6-21 mg/dL
Reference values have not been established for patients who are <12 months of age.
Clinical References: Tietz Textbook of Clinical Chemistry. Fourth edition. Edited by CA Burtis, ER
Ashwood, DE Bruns. WB Saunders Company, Philadelphia, 2006;24:801-803
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 314
immune response to allergens that may be associated with allergic disease. The allergens chosen for
testing often depend upon the age of the patient, history of allergen exposure, season of the year, and
clinical manifestations. In individuals predisposed to develop allergic disease, the sequence of
sensitization and clinical manifestations proceed as follows: eczema and respiratory disease (rhinitis and
bronchospasm) in infants and children less than 5 years due to food sensitivity (milk, egg, soy, and wheat
proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Carrier screening for Bloom syndrome in individuals of Ashkenazi Jewish ancestry
Confirmation of suspected clinical diagnosis of Bloom syndrome in individuals of Ashkenazi Jewish
ancestry Prenatal diagnosis for Bloom syndrome in at-risk pregnancies
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 315
Clinical References: 1. Gross SJ, Pletcher BA, Monaghan KG: Carrier screening in individuals of
Ashkenazi Jewish descent. Genet Med 2008 Jan;10(1):54-6 2. Hickson ID: RecQ helicases: Caretakers of
the genome. Nat Rev Cancer 2003;3(3):169-178
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical utility
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 316
of food-specific IgG tests has not been established. These tests can be used in special clinical situations to
select foods for evaluation by diet elimination and challenge in patients who have food-related
complaints. It should be recognized that the presence of food-specific IgG alone cannot be taken as
evidence of food allergy and only indicates immunologic sensitization by the food allergen in question.
This test should only be ordered by physicians who recognize the limitations of the test.
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 317
third decade of life, although some patients present with a more severe infantile-onset form of the
disease. JPS is inherited in an autosomal dominant fashion, although a significant proportion of
probands have no family history. Approximately 50% of patients with JPS have an identifiable mutation
in the SMAD4 or BMPR1A genes.
Useful For: Confirmation of juvenile polyposis syndrome for patients with clinical features This test
should be ordered only for individuals with symptoms suggestive of juvenile polyposis syndrome.
Asymptomatic patients with a family history of juvenile polyposis syndrome should not be tested until a
mutation has been identified in an affected family member.
Interpretation: All detected alterations are evaluated according to American College of Medical
Genetics recommendations.(1) Variants are classified based on known, predicted, or possible
pathogenicity and reported with interpretive comments detailing their potential or known significance.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for
standards of interpretation and reporting of sequence variations: revisions 2007. Genet Med
2008:10(4):294-300 2. Lammi L, Arte S, Somer M, et al: Mutations in AXIN2 Cause Familial Tooth
Agenesis and Predispose to Colorectal Cancer. Am J Hum Genet 2004;74:1043-1050 3. Liu W, Dong X,
Mai M, et al: Mutations in AXIN2 cause colorectal cancer with defective mismatch repair by activating
beta-catenin/TCF signaling. Nat Genet 2000;26:146-147 4. Mai M, Qian C, Yokomizo A, et al: Cloning
of the human homolog of conductin (AXIN2), a gene mapping to chromosome 17q23-q24. Genomics
1998;55:341-344 5. Dong X, Seelan RS, Qian C, et al: Genomic structure, chromosome mapping and
expression analysis of the human AXIN2 gene. Cytogenet Cell Genet 2001;93:26-28
Clinical References: 1. McCune RC, Syrbu SE, Vasef MA: Expression profiling of transcription
factors Pax-5, Oct-1, Oct-2, BOB.1, and PU.1 in Hodgkin's and non-Hodgkin's lymphomas: a
comparative study using high throughput tissue microarrays. Mod Pathol 2006;19:1010-1018 2. Abd El
All HS: BOB-1 is expressed in classic Hodgkin lymphoma. Diagn Pathol 2007 Mar 8;2:1-10 3.
Loddenkemper C, Anagnostopoulos I, Hummell M, et al: Differential Eu enhancer activity and expression
of BOB.1/OBF.1, Oct 2, PU.1, and immunoglobulin in reactive B-cell populations, B-cell non-Hodgkin
lymphomas and Hodgkin lymphomas. J Pathol 2004 Jan;202(1):60-69 4. Marafioti T, Ascani S, Pulford
K, et al: Expression of B-lymphocyte-associated transcription factors in human T-cell neoplasms. Am J
Pathol 2003 Mar;162(3):861-871
Useful For: Diagnosis and assessment of severity of metabolic bone disease including Paget disease,
osteomalacia, and other states of high bone turnover Monitoring efficacy of antiresorptive therapies
including postmenopausal osteoporosis treatment
Interpretation: Bone alkaline phosphatase (BAP) concentration is high in Paget disease and
osteomalacia. Antiresorptive therapies lower BAP from baseline measurements in Paget disease,
osteomalacia, and osteoporosis. Several studies have shown that antiresorptive therapies for
management of osteoporosis patients should result in at least a 25% decrease in BAP within 3 to 6
months of initiating therapy.(2,3) BAP also decreases following antiresorptive therapy in Paget
disease.(4) When used as a marker for monitoring purposes, it is important to determine the critical
difference (or least significant change). The critical difference is defined as the difference between 2
determinations that may be considered to have clinical significance. The critical difference for this
method was calculated to be 25% with a 95% confidence level.(1)
Reference Values:
Males
<2 years: 25-221 mcg/L
2-9 years: 27-148 mcg/L
10-13 years: 35-169 mcg/L
14-17 years: 13-111 mcg/L
Adults: < or =20 mcg/L
Females
<2 years: 28-187 mcg/L
2-9 years: 31-152 mcg/L
10-13 years: 29-177 mcg/L
14-17 years: 7-41 mcg/L
Adults
Premenopausal: < or =14 mcg/L
Postmenopausal: < or =22 mcg/L
Clinical References: 1. Kress BC: Bone alkaline phosphatase: methods of quantitation and clinical
utility. J Clin Ligand Assay 1998;21(2):139-148 2. Kress BC, Mizrahi IA, Armour KW, et al: Use of
bone alkaline phosphatase to monitor alendronate therapy in individual postmenopausal osteoporotic
women. Clin Chem 1999;45(7):1009-1017 3. Garnero P, Darte C, Delmas PD: A model to monitor the
efficacy of alendronate treatment in women with osteoporosis using a biochemical marker of bone
turnover. Bone 1999;24(6):603-609 4. Raisz L, Smith JA, Trahiotism M, et al: Short-term risedronate
treatment in postmenopausal women: Effects on biochemical markers of bone turnover. Osteoporos Int
2000;11:615-620
Useful For: Undetermined metabolic bone disease Renal osteodystrophy Osteomalacia Osteoporosis
Paget's disease Assessing effects of therapy Identification of some disorders of the hematopoietic system
Aluminum toxicity Presence of iron in the bone
Reference Values:
The laboratory will provide an interpretive report.
The report will be sent to the physician designated on the Bone Histomorphometry: Patient Information.
Clinical References: Recker RR: Bone Histomorphometry: Techniques and Interpretation. Boca
Raton,FL, CRC Press, 1983
Useful For: Undetermined metabolic bone disease Renal osteodystrophy Osteomalacia Osteoporosis
Paget's disease Assessing effects of therapy Identification of some disorders of the hematopoietic system
Aluminum toxicity Presence of iron in the bone
Reference Values:
The laboratory will provide a quantitative and an interpretive report.
The report will be sent to the physician designated on the Bone Histomorphometry: Patient Information.
Clinical References: Recker RR: Bone Histomorphometry: Techniques and Interpretation. Boca
Raton, FL, CRC Press, 1983
Useful For: Preferred diagnostic test for the detection of Bordetella pertussis or Bordetella
parapertussis
Interpretation: A positive result indicates the presence of DNA from Bordetella pertussis or
Bordetella parapertussis. In some cases, a patient may test positive for both Bordetella pertussis and
Bordetella parapertussis. Cross-reactivity with Bordetella holmesii and Bordetella bronchiseptica may
occur with the Bordetella pertussis assay (see Cautions). A negative result indicates the absence of
detectable Bordetella pertussis and Bordetella parapertussis DNA in the specimen but does not negate
the presence of organism or active or recent disease (known inhibition rate of <1%) and may occur due
to inhibition of PCR, sequence variability underlying primers and/or probes, or the presence of
Bordetella pertussis or Bordetella parapertussis in quantities less than the limit of detection of the assay.
Additionally, patients presenting late after symptom onset may test negative; in such cases, testing for
Bordetella pertussis antibody, IgG, in serum may be considered.
Reference Values:
Not applicable
Clinical References: 1. Theofiles AG, Cunningham SA, Chia N, et al: Pertussis outbreak,
southeastern Minnesota, 2012. Mayo Clin Proc 2014 Oct;89(10):1378-1388 2. Guthrie JL, Robertson
AV, Tang P, et al: Novel duplex real-time PCR assay detects Bordetella holmesii in specimens from
patients with pertussis-like symptoms in Ontario, Canada. J Clin Microbiol 2010;48:1435-1437 3. Sloan
LM, Hopkins MK, Mitchell PS, et al: Multiplex LightCycler PCR assay for detection and differentiation
of Bordetella pertussis and Bordetella parapertussis in nasopharyngeal specimens. J Clin Microbiol
2002;40:96-100
Useful For: Diagnosis of recent infection with Bordetella pertussis in patients with > or =2 weeks of
symptoms consistent with whooping cough
Interpretation: Negative (<40 IU/mL): No IgG antibodies to pertussis toxin (PT) detected. Results
may be falsely negative in patients with <2 weeks of symptoms. Borderline (40-<100 IU/mL):
Recommend follow-up testing in 10 to 14days if clinically indicated. Positive (> or =100 IU/mL): IgG
antibodies to pertussis toxin (PT) detected. Results suggest recent infection with or recent vaccination
against Bordetella pertussis.
Reference Values:
> or =100 IU/mL (positive)
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 321
> or = 40-<100 IU/mL (borderline)
<40 IU/mL (negative)
Clinical References: 1. Leber AL: Pertussis: relevant species and diagnostic update. Clin Lab Med
2014;34:237-255 2. Guiso N, Berbers G, Fry NK, et al: What to do and what not to do in serological
diagnosis of pertussis: recommendation from EU reference laboratories. Eur J Clin Microbiolo Infect Dis
2011;30(3):307-312 3. Andre P, Caro V, Njamkepo E, et al: Comparison of serological and real-time PCR
assays to diagnose Bordetella pertussis infection in 2007. J Clin Microbiol 2008;46(5):1672-1677
Useful For: Aids in the diagnosis of Borrelia miyamotoi infection in conjunction with clinical findings
Interpretation: A positive result indicates the presence of Borrelia miyamotoi DNA and is consistent
with active or recent infection. While positive results are highly specific indicators of disease, they should
be correlated with symptoms and clinical findings of tick-borne relapsing fever.
Reference Values:
Negative
Clinical References: 1. Gugliotta JL, Goethert HK, Berardi VP, Telford SR, III:
Meningoencephalitis from Borrelia miyamotoi in an Immunocompromised Patient. N Engl J Med
2013;368:240-245 2. Fomenko NV, Borgoyakov VY, Panov VV: Genetic Features of DNA of Borrelia
miyamotoi Transmitted by Ixodes persulcatus. Mol Gen Microbiol Virol 2011;26:60-65 3. Platonov AE,
Karan LS, Kolyasnikova NM, et al: Humans Infected with Relapsing Fever Spirochete Borrelia
miyamotoi, Russia. Emerg Infect Dis 2011;17:1816-1823
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 322
Useful For: Aids in the diagnosis of Borrelia miyamotoi infection in conjunction with clinical
findings
Interpretation: A positive result indicates the presence of Borrelia miyamotoi DNA and is
consistent with active or recent infection. While positive results are highly specific indicators of disease,
they should be correlated with symptoms and clinical findings of tick-borne relapsing fever.
Reference Values:
Negative
Clinical References: 1. Gugliotta JL, Goethert HK, Berardi VP, Telford SR, III:
Meningoencephalitis from Borrelia miyamotoi in an Immunocompromised Patient. N Engl J Med
2013;368:240-245 2. Fomenko NV, Borgoyakov VY, Panov VV: Genetic Features of DNA of Borrelia
miyamotoi Transmitted by Ixodes persulcatus. Mol Gen Microbiol Virol 2011;26:60-65 3. Platonov AE,
Karan LS, Kolyasnikova NM, et al: Humans Infected with Relapsing Fever Spirochete Borrelia
miyamotoi, Russia. Emerg Infect Dis 2011;17:1816-1823
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 323
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 324
sensitization and clinical manifestations proceed as follows: eczema and respiratory disease (rhinitis and
bronchospasm) in infants and children less than 5 years due to food sensitivity (milk, egg, soy, and wheat
proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 325
with the help of brachyury, a molecule required for notochordal differentiation. Skeletal Radiol
2007;36(1):59-65
Useful For: Identification of melanoma tumors that may respond to BRAF-targeted therapies
Interpretation: An interpretative report will be provided.
Clinical References: 1. Anderson S, Bloom KJ, Vallera DU, et al: Multisite analytic performance
studies of a real-time polymerase chain reaction assay for the detection of BRAF V600E mutations in
formalin-fixed paraffin-embedded tissue specimens of malignant melanoma. Arch Pathol Lab Med 2012
Feb;136:1-7 2. Chapman PB, Hauschild A, Robert C, et al: BRIM-3 Study Group. Improved survival with
vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011 Jun;364(26):2507-2516 3.
Package insert: Cobas 4800 V600 Mutation Test. Roche Molecular Systems, Inc., Branchburg, NJ;
February 2011 4. Dhomen N, Marais R: BRAF signaling and targeted therapies in melanoma. Hematol
Oncol Clin North Am 2009 Jun;23(3):529-545, ix 5. Flaherty KT, Puzanov I, Kim KB, et al: Inhibition of
mutated, activated BRAF in metastatic melanoma. N Engl J Med 2010 Aug;363(9):809-819
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 326
(V600E) has been shown to be present in approximately 70% of tumors with hypermethylation of the
MLH1 promoter. Importantly, the V600E mutation has not been identified to date in cases with germline
MLH1 mutations. Thus, direct assessment of MLH1 promoter methylation status and testing for the
BRAF V600E mutation can be used to help distinguish between a germline mutation and
epigenetic/somatic inactivation of MLH1. Tumors that have the BRAF V600E mutation and demonstrate
MLH1 promoter hypermethylation are almost certainly sporadic, whereas tumors that show neither are
most often caused by an inherited mutation. Although testing for the BRAF V600E mutation and MLH1
promoter hypermethylation are best interpreted together, they are also available separately to
accommodate various clinical situations and tumor types. These tests can provide helpful diagnostic
information when evaluating an individual suspected of having HNPCC/Lynch syndrome, especially
when testing is performed in conjunction with MSIHC / Microsatellite Instability
(MSI)/Immunohistochemistry (IHC) Profile-Lynch/Hereditary Nonpolyposis Colorectal Cancer (HNPCC)
Screen, which includes MSI and IHC studies. It should be noted that these tests are not genetic tests, but
rather stratify the risk of having an inherited cancer predisposition and identify patients who might benefit
from subsequent genetic testing. See Hereditary Nonpolyposis Colorectal Cancer Testing Algorithm in
Special Instructions. Also, see Hereditary Colorectal Cancer: Hereditary Nonpolyposis Colon Cancer
(November 2005, Communique') in Publications. Assessment for the BRAF V600E mutation has
alternative clinical utilities. BRAF is part of the epidermal growth factor receptor (EGFR) signaling
cascade, which plays a role in cell proliferation. Dysregulation of this pathway is a key factor in tumor
progression. Targeted therapies directed to components of this pathway have demonstrated some success
(increased progression-free and overall survival) in treating patients with certain tumors. Effectiveness of
these therapies, however, depends in part on the mutation status of the pathway components.
Clinical References: 1. Cunningham JM, Kim CY, Christensen ER, et al: The frequency of
hereditary defective mismatch repair in a prospective series of unselected colorectal carcinomas. Am J
Hum Genet 2001;69:780-790 2. Wang L, Cunningham JM, Winters JL, et al: BRAF mutations in colon
cancer are not likely attributable to defective DNA mismatch repair. Cancer Res 2003; 63:5209-5212 3.
Domingo E, Laiho P, Ollikainen M, et al: BRAF screening as a low-cost effective strategy for
simplifying HNPCC genetic testing. J Med Genet 2004;41:664-668 4. Di Nicolantonio F, Martini M,
Molinari F, et al: Wild-type BRAF is required for response to Panitumumab or Cetuximab in metastatic
colorectal cancer. J Clin Oncol 2008; 26:5705-5712 5. Flaherty KT, Puzanov I, Kim KB, et al:
Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med 2010;363(9):809-819
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 327
Useful For: Identification of BRAF V600E mutated protein
Interpretation: This test includes only technical performance of the stain (no pathologist interpretation
is performed). If diagnostic consultation by a pathologist is required, order 70012 / Pathology
Consultation. The positive and negative controls are verified as showing appropriate immunoreactivity. If
a control tissue is not included on the slide, a scanned image of the relevant quality control tissue is
available upon request; contact 855-516-8404. Interpretation of this test should be performed in the
context of the patient's clinical history and other diagnostic tests by a qualified pathologist.
Clinical References: 1. Ida C, Vrana JA, Rodriguez FJ, et al: Immunohistochemistry is highly
sensitive and specific for detection of BRAF V600E mutation in pleomorphic xanthoastrocytoma. Acta
Neuopath communications 2013;1:20 2. Capper D, Berghoff AS, Magerle M, et al: Immunohistochemical
testing of BRAF V600E status in 1,120 tumor tissue samples of patients with brain metastases. Acta
Neuropathol 2012;123(2):223-233 3. Andrulis M, Penzel R, Weichert W, et al: Application of a BRAF
V600E Mutation-specific Antibody for the Diagnosis of Hairy Cell Leukemia. Am J Surg Pathol
2012;36(12):1796-1800 4. Koperek O, Kornauth C, Capper D, et al: Immunohistochemical detection of
the BRAF V600E-mutated protein in papillary thyroid carcinoma. Am J Surg Pathol 2012;36(6):844-850
5. Skorokhod A, Capper D, von Deimling A, et al: Detection of BRAF V600E mutations in skin
metastases of malignant melanoma by monoclonal antibody VE1. J Am Acad skin metastases of
malignant melanoma by monoclonal antibody VE1. J Am Acad Dermatol 2012;67(3):488-491
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 328
6 > or =100 Strongly positive Reference values
apply to all ages.
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: Establishing a diagnosis of hereditary breast and ovarian cancer (HBOC) Identification
of familial BRCA1 or BRCA2 mutation to allow for predictive testing in family members
Interpretation: All detected alterations are evaluated according to American College of Medical
Genetics and Genomics recommendations.(2) Variants are classified based on known, predicted, or
possible pathogenicity and reported with interpretive comments detailing their potential or known
significance.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Petrij-Bosch A, Peelen T, van Vliet M, et al: BRCA1 genomic deletions
are major founder mutations in Dutch breast cancer patients. Nat Genet 1997 Nov;17(3):341-345 2.
Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for standards for interpretation
and reporting of sequence variations: Revisions 2007. Genet Med 2008;10(4):294-300 3. Lindor NM,
McMaster ML, Lindor CJ, et al: Concise Handbook of Familial Cancer Susceptibility Syndromes.
Second Edition. J Natl Cancer Inst Monogr 2008;(38):1-93 4. BRCA1 and BRCA2 Hereditary Breast
and Ovarian Cancer-GeneReviews-NCBI Bookshelf. Accessed 6/1/2015. Available at
http://www.ncbi.nlm.nih.gov/books/NBK1247/ 5. NCCN Clinical Practice Guidelines in Oncology
(NCCN Guidelines): Genetic/Familial High-Risk Assessment: Breast and Ovarian Version 1.2015.
Accessed 6/1/2015. Available at www.nccn.org 6. Chen S, Parmigiani G: Meta-analysis of BRCA1 and
BRCA2 penetrance. J Clin Oncol 2007 Apr 10;25(11):1329-1333 7. Saslow D, Boetes C, Burke W, et
al: American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography.
CA Cancer J Clin 2007 Mar-Apr;57(2):75-89
Useful For: FDA-approved cancer-associated antigen (CA 27.29) for serial testing in women with
prior stage II or III breast cancer who are clinically free of disease Predicting early recurrence of disease
in women with treated carcinoma of the breast As an indication that additional tests or procedures should
be performed to confirm recurrence of breast cancer
Interpretation: Increased levels of cancer-associated antigen (CA 27.29) (>38 U/mL) may indicate
recurrent disease in a woman with treated breast carcinoma.
Reference Values:
Males
> or =18 years: < or =38.0 U/mL (use not defined)
Females
> or =18 years: < or =38.0 U/mL
Reference values have not been established for patients who are <18 years of age.
Serum markers are not specific for malignancy, and values may vary by method.
Clinical References: 1. Bon GG, Von Mensdorff-Pouilly S, Kenemans P, et al: Clinical and
technical evaluation of ACS BR serum assay of MUC1 gene-derived glycoprotein in breast cancer, and
comparison with CA 15-3 assays. Clin Chem 1997;43:585-593 2. Chan DW, Beveridge RA, Muss H, et
al: Use of Truquant BR radioimmunoassay for early detection of breast cancer recurrence in patients with
stage II and stage III disease. J Clin Oncol 1997;15:2322-2328
Useful For: Useful in the diagnosis of ovarian small cell carcinoma of hypercalcemic type (SCCOHT)
Interpretation: This test includes only technical performance of the stain (no pathologist interpretation
is performed). If diagnostic consultation by a pathologist is required order 70012 / Pathology
Consultation. The positive and negative controls are verified as showing appropriate immunoreactivity. If
a control tissue is not included on the slide, a scanned image of the relevant quality control tissue is
available upon request. Please contact 855-516-8404. Interpretation of this test should be performed in the
context of the patient's clinical history and other diagnostic tests by a qualified pathologist.
Clinical References: 1. Clarke BA, Witkowski L, Ton Nu TN, et al: Loss of SMARCA4 (BRG1)
Protein Expression by Immunohistochemistry in Small Cell Carcinoma of the Ovary, Hypercalcemic
Type Distinguishes these Tumors from their Mimics. Histopathology 2016 Apr 21 2. Conlon N, Silva A,
Guerra E et al: Loss of SMARCA4 Expression Is Both Sensitive and Specific for the Diagnosis of Small
Cell Carcinoma of Ovary, Hypercalcemic Type. Am J Pathol 2016;40:395-403 3. Karanian-Philippe M,
Velasco V, Longy M et al: SMARCA4 (BRG1) Loss of Expression Is a Useful Marker for the Diagnosis
of Ovarian Small Cell Carcinoma of the Hypercalcemic Type (Ovarian Rhabdoid Tumor). Am J Surg
Pathol 2015;39:1197-1205 4. Ramos P, Karnezls A, Craig D et al: Small Cell Carcinoma of the Ovary,
Hypercalcemic Type, Displays Frequent Inactivating Germline and Somatic Mutations in SMARCA4.
Nat Genet 2014;46(5):427-430
Useful For: Detecting and identifying bacteria (including mycobacteria) from normally sterile
sources, including synovial fluid; body fluids such as pleural, peritoneal and pericardial fluids,
cerebrospinal fluid (CSF); and both fresh and formalin-fixed paraffin-embedded (FFPE) tissues
Interpretation: A positive broad-range PCR/sequencing result indicates that bacterial nucleic acid of
the specified organisms was detected, which may be due to bacterial infection or environmental or
contaminating nucleic acids in the specimen. A negative broad-range PCR/sequencing result indicates
the absence of detectable bacterial (including mycobacterial) nucleic acids in the specimen, but does not
rule-out false-negative results that may occur due to sampling error, sequence variability underlying the
primers, the presence of bacterial nucleic acids in quantities less than the limit of detection of the assay,
or inhibition of PCR. If PCR testing appears to be negative but there is evidence of PCR inhibition,
testing will be repeated. If inhibition is again detected, the result will be reported as "PCR inhibition
present."
Reference Values:
No bacterial DNA detected
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical
utility of food-specific IgG tests has not been established. These tests can be used in special clinical
situations to select foods for evaluation by diet elimination and challenge in patients who have
food-related complaints. It should be recognized that the presence of food-specific IgG alone cannot be
taken as evidence of food allergy and only indicates immunologic sensitization by the food allergen in
question. This test should only be ordered by physicians who recognize the limitations of the test.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 331
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
4 17.5-49.9 Strongly positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 332
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Reference Values:
IgG SCREEN
Negative (reported as positive, negative, or equivocal)
IgM SCREEN
Negative (reported as positive, negative, or equivocal)
Clinical References: 1. Corbel MJ: Brucellosis: an overview. Emerg Infect Dis 1997;3:213-221 2.
Public health consequences of a false-positive laboratory test result for Brucella--Florida, Georgia, and
Michigan, 2005, MMWR Morb Mortal Wkly Rep June 6;2008/57(22);603-605 3. Araj GF, Lulu AR,
Saadah MA, et al: Rapid diagnosis of central nervous system brucellosis by ELISA. J Neuroimmunol
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 333
1986;12:173-182
Reference Values:
Negative (reported as positive or negative)
Clinical References: 1. Mandell GL, Bennett JE, Dolin R: Mandell, Douglas, and Bennett's
Principles and Practice of Infectious Diseases. Fourth edition. New York, Churchill Livingstone, 1995, pp
2053-2060 2. Koneman, EW: Miscellaneous Fastidious Gram-Negative Bacilli. In Color Atlas and
Textbook of Diagnostic Microbiology. Sixth edition. Philadelphia, Lippincott Williams and Wilkins,
2006, pp 482-491
Reference Values:
Negative (reported as positive or negative)
Clinical References: 1. Mandell GL, Bennett JE, Dolin R: Mandell, Douglas, and Bennett's
Principles and Practice of Infectious Diseases. Fourth edition. New York, Churchill Livingstone, 1995, pp
2053-2060 2. Koneman EW: Miscellaneous Fastidious Gram-Negative Bacilli. In Color Atlas and
Textbook of Diagnostic Microbiology. Sixth Edition. Philadelphia, Lippincott, Williams and Wilkins,
2006, pp 482-491
Reference Values:
<1:80
Clinical References: 1. Public health consequences of a false-positive laboratory test result for
Brucella-Florida, Georgia, and Michigan, 2005. MMWR Morb Mortal Wkly Rep 2008 June
6;57(22):603-605 2. Welch RJ, Litwin CM: A comparison of Brucella IgG and IgM ELISA assays with
agglutination methodology. J Clin Lab Anal 2010;24:160-162
Useful For: Providing a genetic evaluation for patients with a personal or family history suggestive of
Brugada syndrome (BrS) Establishing a diagnosis of a BrS, in some cases, allowing for appropriate
management and surveillance for disease features based on the gene involved Identifying variants within
genes known to be associated with increased risk for disease features and allowing for predictive testing
of at-risk family members
Interpretation: Evaluation and categorization of variants is performed using the most recent published
American College of Medical Genetics and Genomics (ACMG) recommendations as a guideline. Variants
are classified based on known, predicted, or possible pathogenicity and reported with interpretive
comments detailing their potential or known significance. Multiple in silico evaluation tools may be used
to assist in the interpretation of these results. The accuracy of predictions made by in silico evaluation
tools is highly dependent upon the data available for a given gene, and predictions made by these tools
may change over time. Results from in silico evaluation tools should be interpreted with caution and
professional clinical judgment.
Reference Values:
An interpretive report will be provided.
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 336
responsible for eliciting signs and symptoms. The level of IgE antibodies in serum varies directly with the
concentration of IgE antibodies expressed as a class score or kU/L.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 337
an anti-Btk monoclonal antibody was developed by Futatani et al, which was used to evaluate both
XLA patients and carriers.(7) In this study, 41 unrelated XLA families were studied and deficient Btk
protein expression was seen in 40 of these 41 patients, with complete Btk deficiency in 35 patients and
partial Btk deficiency in 5 patients. One patient had a normal level of Btk protein expression. The 6
patients with partial or normal Btk expression had missense BTK mutations. Additionally, the flow
cytometry assay detected carrier status in the mothers of 35 of the 41 patients (approximately 85%). In
the 6 patients where the Btk expression was normal in the mothers of XLA patients, it was noted that all
these patients were sporadic cases without previous family history of the disease.(7) It appears,
therefore, that most BTK mutations result in deficient expression of Btk protein, which can be detected
by flow cytometry in monocytes.(7,8) Also, the mosaic expression of Btk protein in the monocytes by
flow cytometry is potentially useful in the diagnosis of female carriers.(8) The flow cytometry test
therefore provides a convenient screening tool for the diagnosis of XLA with confirmation of the
diagnosis by BTK genotyping.(7,8) In the rare patient with the clinical features of XLA but normal Btk
protein expression, BTK genotyping must be performed to determine the presence of a mutation. A
diagnosis of XLA should be suspected in males with 1) early-onset bacterial infections, 2) marked
reduction in all classes of serum immunoglobulins, and 3) absent B cells (CD19+ cells). The decrease in
numbers of peripheral B cells is a key feature, though this also can be seen in a small subset of patients
with common variable immunodeficiency (CVID). As well, some BTK mutations can preserve small
numbers of circulating B cells and, therefore, all the 3 criteria mentioned above need to be evaluated.
Patients should be assessed for the presence of Btk protein by flow cytometry, although normal results
by flow cytometry do not rule out the presence of a BTK mutation with aberrant protein function
(despite normal protein expression). The diagnosis is established or confirmed only in those individuals
who have a mutation identified in the BTK gene by gene sequencing or who have male family members
with hypogammaglobulinemia with absent or low B cells. Appropriate clinical history is required with
or without abnormal Btk protein results by flow cytometry. It was shown that there are XLA patients
with mothers who have normal Btk protein expression by flow cytometry and normal BTK genotyping
and that the mutation in the patient is a result of de novo mutations in the maternal germline. In the
same study, it was shown that there can be female carriers who have normal Btk protein expression but
are genetically heterozygous and they do not show abnormal protein expression due to extreme skewed
inactivation of the mutant X-chromosome.(6) Also, the presence of 1 copy of the normal BTK gene and
associated normal Btk protein can stabilize mutant protein abrogating the typical bimodal pattern of
protein expression seen in female carriers. Therefore, female carrier status can only conclusively be
determined by genetic testing, especially if the Btk protein flow test is normal. It is important to keep in
mind that the mere presence of BTK gene mutations does not necessarily correlate with a diagnosis of
XLA unless the appropriate clinical and immunological features are present.(9,10)
Useful For: Preferred test for confirming a diagnosis of X-linked agammaglobulinemia (XLA) in
males with a history of recurrent sinopulmonary infections, profound hypogammaglobulinemia, and <1%
peripheral B cells In females, this is the most useful test for identifying carriers of XLA. By including
protein and gene analysis, this test provides a comprehensive assessment and enables appropriate
genotype-phenotype correlations.
BTK: Bruton tyrosine kinase (Btk) expression will be reported as present, absent, partial deficiency, or
mosaic (carrier).
Clinical References: 1. Tsukada S, Saffran DC, Rawlings DJ, et al: Deficient expression of a B cell
cytoplasmic tyrosine kinase in human X-linked agammaglobulinemia. Cell 1993;72:279-290 2. Noordzij
JG, de Bruin-Versteeg S, Comans-Bitter WM, et al: Composition of precursor B-cell compartment in
bone marrow from patients with X-linked agammaglobulinemia compared with health children. Pediatr
Res 2002;2:159-168 3. Conley ME, Broides A, Hernandez-Trujillo V, et al: Genetic analysis of patients
with defects in early B-cell development. Immunol Rev 2005;203:216-234 4. Lindvall JM, Blomberg
KEM, Vargas L, et al: Bruton's tyrosine kinase: cell biology, sequence conservation, mutation spectrum,
siRNA modifications, and expression profiling. Immunol Rev 2005;203:200-215 5. Valiaho J, Smith CI,
Vihinen M: BTKbase: The mutation database for X-linked agammaglobulinemia. Hum Mutat
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 338
2006;27:1209-1217 6. Takada H, Kanegane H, Nomura A, et al: Female agammaglobulinemia due to the
Bruton's tyrosine kinase deficiency caused by extremely skewed X-chromosome inactivation. Blood
2004;103:185-187 7. Futatani T, Miyawaki T, Tsukada S, et al: Deficient expression of Bruton's tyrosine
kinase in monocytes from X-linked agammaglobulinemia as evaluated by a flow cytometric analysis and
its clinical application to carrier detection. Blood 1998;91(2):595-602 8. Kanegane H, Futatani T, Wang
Y, et al: Clinical and mutational characteristics of X-linked agammaglobulinemia and its carrier identified
by flow cytometric assessment combined with genetic analysis. J Allergy Clin Immunol
2001;108:1012-1020 9. Graziani S, Di Matteo G, Benini L, et al: Identification of a BTK mutation in a
dysgammaglobulinemia patient with reduced B cells: XLA or not? Clin Immunol 2008;128:322-328 10.
Fleisher TA, Notarangelo LD: What does it take to call it a pathogenic mutation? Clin Immunol
2008;128:285-286
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 339
flow cytometry is potentially useful in the diagnosis of female carriers.(8) The flow cytometry test
therefore provides a convenient screening tool for the diagnosis of XLA with confirmation of the
diagnosis by BTK genotyping.(7,8) In the rare patient with the clinical features of XLA but normal Btk
protein expression, BTK genotyping must be performed to determine the presence of a mutation. A
diagnosis of XLA should be suspected in males with 1) early-onset bacterial infections, 2) marked
reduction in all classes of serum immunoglobulins, and 3) absent B cells (CD19+ cells). The decrease in
numbers of peripheral B cells is a key feature, though this also can be seen in a small subset of patients
with common variable immunodeficiency (CVID). As well, some BTK mutations can preserve small
numbers of circulating B cells and, therefore, all the 3 criteria mentioned above need to be evaluated.
Patients should be assessed for the presence of Btk protein by flow cytometry, although normal results
by flow cytometry do not rule out the presence of a BTK mutation with aberrant protein function
(despite normal protein expression). The diagnosis is established or confirmed only in those individuals
who have a mutation identified in the BTK gene by gene sequencing or who have male family members
with hypogammaglobulinemia with absent or low B cells. Appropriate clinical history is required with
or without abnormal Btk protein results by flow cytometry. It was shown that there are XLA patients
with mothers who have normal Btk protein expression by flow cytometry and normal BTK genotyping
and that the mutation in the patient is a result of de novo mutations in the maternal germline. In the
same study, it was shown that there can be female carriers who have normal Btk protein expression but
are genetically heterozygous, and they do not show abnormal protein expression due to extreme skewed
inactivation of the mutant X chromosome.(6) Also, the presence of 1 copy of the normal BTK gene and
associated normal Btk protein can stabilize mutant protein abrogating the typical bimodal pattern of
protein expression seen in female carriers. Therefore, female carrier status can only conclusively be
determined by genetic testing, especially if the Btk protein flow test is normal. It is important to keep in
mind that the mere presence of BTK gene mutations does not necessarily correlate with a diagnosis of
XLA unless the appropriate clinical and immunological features are present.(9,10)
Useful For: Preferred test for confirming a diagnosis of X-linked agammaglobulinemia (XLA) in male
family members of affected individuals with known BTK mutations Preferred test for determining carrier
status of female relatives of male XLA patients with known BTK mutations By including protein and
gene analysis, this test provides a comprehensive assessment and enables appropriate genotype-phenotype
correlations.
BTK: Bruton tyrosine kinase (Btk) expression will be reported as present, absent, partial deficiency, or
mosaic (carrier).
Clinical References: 1. Tsukada S, Saffran DC, Rawlings DJ, et al: Deficient expression of a B cell
cytoplasmic tyrosine kinase in human X-linked agammaglobulinemia. Cell 1993;72:279-290 2. Noordzij
JG, de Bruin-Versteeg S, Comans-Bitter WM, et al: Composition of precursor B-cell compartment in
bone marrow from patients with X-linked agammaglobulinemia compared with health children. Pediatr
Res 2002;2:159-168 3. Conley ME, Broides A, Hernandez-Trujillo V, et al: Genetic analysis of patients
with defects in early B-cell development. Immunol Rev 2005;203:216-234 4. Lindvall JM, Blomberg
KEM, Vargas L, et al: Bruton's tyrosine kinase: cell biology, sequence conservation, mutation spectrum,
siRNA modifications, and expression profiling. Immunol Rev 2005;203:200-215 5. Valiaho J, Smith CI,
Vihinen M: BTKbase: The mutation database for X-linked agammaglobulinemia. Hum Mutat
2006;27:1209-1217 6. Takada H, Kanegane H, Nomura A et al: Female agammaglobulinemia due to the
Bruton's tyrosine kinase deficiency caused by extremely skewed X-chromosome inactivation. Blood
2004;103:185-187 7. Futatani T, Miyawaki T, Tsukada S, et al: Deficient expression of Bruton's tyrosine
kinase in monocytes from X-linked agammaglobulinemia as evaluated by a flow cytometric analysis and
its clinical application to carrier detection. Blood 1998;91(2):595-602 8. Kanegane H, Futatani T, Wang
Y, et al: Clinical and mutational characteristics of X-linked agammaglobulinemia and its carrier identified
by flow cytometric assessment combined with genetic analysis. J Allergy Clin Immunol
2001;108:1012-1020 9. Graziani S, Di Matteo G, Benini L et al: Identification of a BTK mutation in a
dysgammaglobulinemia patient with reduced B cells: XLA or not? Clin Immunol 2008;128:322-328 10.
Fleisher TA, Notarangelo LD: What does it take to call it a pathogenic mutation? Clin Immunol
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 340
2008;128:285-286
Useful For: Confirming a diagnosis of X-linked agammaglobulinemia (XLA) in male patients with a
history of recurrent sinopulmonary infections, profound hypogammaglobulinemia, and <1% peripheral
B cells, with or without abnormal Bruton tyrosine kinase (Btk) protein expression by flow cytometry
Follow-up testing when evaluating symptomatic male family members with an abnormal or equivocal
result for Btk-protein expression by flow cytometry (BTK / Bruton Tyrosine Kinase [Btk], Protein
Expression, Flow Cytometry, Blood) Evaluating for the presence of BTK mutations in female relatives
(of male XLA patients) who do not demonstrate carrier phenotype by Btk flow cytometry Because
genotype-phenotype correlation is important for the diagnosis of XLA, the preferred test for confirming
a diagnosis of XLA in males and identifying carrier females is BTKFP / Bruton Tyrosine Kinase (BTK)
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 341
Genotype and Protein Analysis, Full Gene Sequence and Flow Cytometry
Clinical References: 1. Tsukada S, Saffran DC, Rawlings DJ, et al: Deficient expression of a B cell
cytoplasmic tyrosine kinase in human X-linked agammaglobulinemia. Cell 1993 Jan 29;72(2):279-290 2.
Noordzij JG, de Bruin-Versteeg S, Comans-Bitter WM, et al: Composition of precursor B-cell
compartment in bone marrow from patients with X-linked agammaglobulinemia compared with healthy
children. Pediatr Res 2002 Feb;51(2):159-168 3. Conley ME, Broides A, Hernandez-Trujillo V, et al:
Genetic analysis of patients with defects in early B-cell development. Immunol Rev 2005
Feb;203:216-234 4. Lindvall JM, Blomberg KE, Valiaho J, et al: Brutons tyrosine kinase: cell
biology, sequence conservation, mutation spectrum, siRNA modifications, and expression profiling.
Immunol Rev 2005 Feb;203:200-215 5. Valiaho J, Smith CI, Vihinen M: BTKbase: the mutation database
for X-linked agammaglobulinemia. Hum Mutat 2006 Dec;27(12):1209-1217 6. Takada H, Kanegane H,
Nomura A, et al: Female agammaglobulinemia due to the Bruton tyrosine kinase deficiency caused by
extremely skewed X-chromosome inactivation. Blood 2004 Jan 1;103(1):185-187
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 342
carrier females requires testing for the Btk protein expression on B cells by flow cytometry and genetic
testing for a BTK mutation. Patients can be screened for the presence of Btk protein by flow cytometry
(BTK / Bruton Tyrosine Kinase [Btk], Protein Expression, Flow Cytometry, Blood); however, normal
results by flow cytometry do not rule out the presence of a BTK mutation with normal protein expression
but aberrant protein function. The diagnosis is confirmed only in those individuals with appropriate
clinical history who have a mutation identified within BTK by gene sequencing or who have other male
family members with hypogammaglobulinemia with absent or low B cells.
Useful For: As a follow-up confirmatory genetic test for relatives of X-linked agammaglobulinemia
(XLA) patients with a previously identified Bruton tyrosine kinase gene (BTK) mutation, after
abnormal Btk protein expression has been previously demonstrated (eg, BTK / Bruton Tyrosine Kinase
[Btk], Protein Expression, Flow Cytometry, Blood) Because genotype-phenotype correlations are
important, the preferred test for confirming a diagnosis of XLA in males and identifying carrier females
in families where a BTK mutation has already been identified is BTKMP / Bruton Tyrosine Kinase
(BTK) Genotype and Protein Analysis, Known Mutation Sequencing and Flow Cytometry, which
provides a comprehensive assessment of both protein and DNA analysis.
Clinical References: 1. Tsukada S, Saffran DC, Rawlings DJ, et al: Deficient expression of a B
cell cytoplasmic tyrosine kinase in human X- linked agammaglobulinemia. Cell 1993 Jan
29;72(2):279-290 2. Noordzij JG, de Bruin-Versteeg S, Comans-Bitter WM, et al: Composition of
precursor B-cell compartment in bone marrow from patients with X-linked agammaglobulinemia
compared with healthy children. Pediatr Res 2002 Feb;51(2):159-168 3. Conley ME, Broides A,
Hernandez-Trujillo V, et al: Genetic analysis of patients with defects in early B-cell development.
Immunol Rev 2005 Feb;203:216-234 4. Lindvall JM, Blomberg KE, Valiaho J, et al: Brutons
tyrosine kinase: cell biology, sequence conservation, mutation spectrum, siRNA modifications, and
expression profiling. Immunol Rev 2005 Feb;203:200-215 5. Valiaho J, Smith CI, Vihinen M:
BTKbase: the mutation database for X-linked agammaglobulinemia. Hum Mutat 2006
Dec;27(12):1209-1217 6. Takada H, Kanegane H, Nomura A, et al: Female agammaglobulinemia due
to the Bruton tyrosine kinase deficiency caused by extremely skewed X-chromosome inactivation.
Blood 2004 Jan 1;103(1):185-187
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of circulating B cells in blood, and profound hypogammaglobulinemia of all isotypes (IgG, IgA, IgM,
and IgE). The clinical presentation includes early onset of recurrent bacterial infections, and absent
lymph nodes and tonsils. Btk plays a critical role in B-cell differentiation. The defect in Btk may be
"leaky" in some patients (ie, a consequence of mutations in the gene that result in a milder clinical and
laboratory phenotype), such that these patients may have some levels of IgG and/or IgM and a small
number of B cells in blood.(1) The vast majority of XLA patients are diagnosed in childhood (median
age of diagnosis in patients with sporadic XLA is 26 months), although some patients are recognized in
early adulthood or later in life. The diagnosis of XLA in both children and adults indicates that the
disorder demonstrates considerable clinical phenotypic heterogeneity, depending on the position of the
mutations within the gene. Females are typically carriers and asymptomatic. Testing in adult females
should be limited to those in their child-bearing years (<45 years). Carrier testing ideally should be
confirmed by genetic testing since it is possible to have a normal flow cytometry test for protein
expression in the presence of heterozygous (carrier) BTK gene mutations. Flow cytometry is a
preliminary screening test for XLA. It is important to keep in mind that this flow cytometry test is only
a screening tool and approximately 20% to 30% of patients who have a mutation within the BTK gene
have normal protein expression (again related to the position of the mutation in the gene and the
antibody used for flow cytometric analysis). Therefore, in addition to clinical correlation, genetic testing
is recommended to confirm a diagnosis of XLA. Furthermore, it is helpful to correlate gene and protein
data with clinical history (genotype-phenotype correlation) in making a final diagnosis of XLA.
Consequently, the preferred test for XLA is BTKFP / Bruton's Tyrosine Kinase (BTK) Genotype and
Protein Analysis, Full Gene Sequence and Flow Cytometry, which includes both flow cytometry and
gene sequencing to confirm the presence of a BTK mutation. If a familial mutation has already been
identified, then BTKMP / Bruton's Tyrosine Kinase (BTK) Genotype and Protein Analysis, Known
Mutation Sequencing and Flow Cytometry should be ordered.
Useful For: Preliminary screening for X-linked agammaglobulinemia (XLA), primarily in male
patients (<65 years of age) or female carriers (child-bearing age: <45 years) Because genotype-phenotype
correlations are important, the preferred test for confirming a diagnosis of XLA in males and identifying
carrier females is: -BTKFP / Bruton's Tyrosine Kinase (BTK) Genotype and Protein Analysis, Full Gene
Sequence and Flow Cytometry -In families where a BTK mutation has already been identified, order
BTKMP / Bruton's Tyrosine Kinase (BTK) Genotype and Protein Analysis, Known Mutation Sequencing
and Flow Cytometry
Interpretation: Results are reported as Bruton tyrosine kinase (Btk) protein expression present
(normal) or absent (abnormal) in monocytes. Additionally, mosaic Btk expression (indicative of a carrier)
and reduced Btk expression (consistent with partial Btk protein deficiency) are reported when present and
correlated with a healthy experimental control. BTK genotyping (BTKS / Bruton's Tyrosine Kinase
(BTK) Genotype, Full Gene Sequence or BTKK / Bruton's Tyrosine Kinase (BTK) Genotype, Known
Mutation) should be performed in the following situations: -To confirm any abnormal flow cytometry
result -In the rare patient with the clinical features of X-linked agammaglobulinemia (XLA), but normal
Btk protein expression -In mothers of patients who do not show the classic carrier pattern of bimodal
protein expression (to determine if there is maternal germinal mosaicism or skewed mutant
X-chromosome inactivation) or there is dominant expression of the normal protein in the presence of 1
copy of a mutation
Reference Values:
Present
Bruton tyrosine kinase (Btk) expression will be reported as present, absent, partial deficiency, or mosaic
(carrier).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
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bronchospasm) in infants and children less than 5 years due to food sensitivity (milk, egg, soy, and
wheat proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Bullous pemphigoid (BP) BP180 and BP230 enzyme-linked immunosorbent assay are
sensitive, objective, and specific tests that should be considered as an initial screening test in the
diagnosis of pemphigoid and its variants. To compare these results with the standard serum test of
indirect immunofluorescence utilizing monkey esophagus substrate.
Interpretation: Antibodies to bullous pemphigoid (BP) BP180 and BP230 have been shown to be
present in most patients with pemphigoid. Adequate sensitivities and specificity for disease are
documented and Mayos experience demonstrates a very good correlation between BP180 and
BP230 results and the presence of pemphigoid (see Supportive Data). However, in those patients
strongly suspected to have pemphigoid, either by clinical findings or by routine biopsy, and in whom
the BP180/BP230 assay is negative, follow-up testing by CIFS / Cutaneous Immunofluorescence
Antibodies (IgG), Serum is recommended. Antibody titer correlates with disease activity in many
patients. Patients with severe disease can usually be expected to have high titers of antibodies to BP.
Titers are expected to decrease with clinical improvement. For further information, see Cutaneous
Immunofluorecence Testing in Special Instructions.
Reference Values:
BP180
<9.0 U (negative)
> or =9.0 U (positive)
BP230
<9.0 U (negative)
> or =9.0 U (positive)
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Clinical References: 1. Liu Z, Diaz LA, Troy JL: A passive transfer model of the organ-specific
autoimmune disease, bullous pemphigoid, using antibodies generated against the hemidesmosomal
antigen, BP180. J Clin Invest 1993;92:2480-2488 2. Matsumura K, Amagai M, Nishikawa T, Hashimoto
T: The majority of bullous pemphigoid and herpes gestationes serum samples react with the NC16a
domain of the e180-kD bullous pemphigoid antigen. Arch Dematol Res 1996;288:507-509 3. Stanley JR,
Hawley-Nelson P, Yuspa SH, et al: Characterization of bullous pemphigoid antigen: a unique basement
membrane protein of stratified aqueous epithelia. Cell 1981;24:897-903 4. Hamada T, Nagata Y, Tmita
M, et al: Bullous pemphigoid sera react specially with various domains of BP230, most frequently with
C-terminal domain, by immunblot analyses using bacterial recombinant proteins covering the entire
molecule. Exp Dermatol 2001;10:256-263
Useful For: Assessment of possible central nervous system or cardiac toxicity associated with use of
bupivacaine or levobupivacaine
Interpretation: In trials with healthy volunteers, the threshold for central nervous system (CNS)
toxicity has been reported at 2.1 (+/- 1.2) mg/L following intravenous infusion,(3) and in another trial, 13
of 14 healthy volunteers reported signs of CNS toxicity at 2.25 mg/L of racemic bupivacaine.(5)
Cardiovascular symptoms were reported in many fewer subjects, indicating slightly higher threshold for
cardiovascular toxicity.
Reference Values:
No established reference values
Clinical References: 1. Physician's Desk Reference (PDR). 61st edition. Montvale, NJ. Thomson
PDR, 2007 2. Baselt RC: Disposition of Toxic Drugs and Chemicals in Man. Seventh edition. Foster City,
CA, Biomedical Publications, 2004, p 1254 3. Knudsen K, Beckman SM, Blomberg S, et al: Central
nervous and cardiovascular effects of i.v. infusions of ropivacaine, bupivacaine and placebo in volunteers.
Br J Anaesth 1997;78:507-514 4. Zink W, Graf BM: The toxicity of local anesthetics: the place of
ropivacaine and levobupivacaine. Curr Opin Anaesthesiol 2008;21:645-650 5. Bardsley H, Gristwood R,
Baker H, et al: A comparison of the cardiovascular effects of levobupivacaine and rac-bupivacaine
following intravenous administration to healthy volunteers. Br J Clin Pharmacol 1998;46:245-429
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BUPMX Buprenorphine and Norbuprenorphine, Chain of Custody,
65215 Urine
Clinical Information: Clinically, buprenorphine is utilized as a substitution therapy for opioid
dependence and as an analgesic. Buprenorphine is a partial agonist of the mu-opioid receptor. These mu
binding sites are discretely distributed in the human brain, spinal cord, and other tissue. The clinical
effects of mu receptor agonists are sedation, euphoria, respiratory depression, and analgesia. As a partial
mu receptor agonist, buprenorphine's clinical effects are decreased, giving buprenorphine a wider safety
margin.(1) Buprenorphine has a prolonged duration of activity. The combination of decreased clinical
effects and prolonged activity gives buprenorphine the added advantage of a delayed and decreased
withdrawal syndrome, compared to other opioids.(1) Compared to morphine, buprenorphine is 25 to 40
times more potent.(1) As with any opioid, abuse is always a concern. To reduce illicit use of
buprenorphine, it is available mixed with naloxone in a ratio of 4:1. When the combination is taken as
prescribed, only small amounts of naloxone will be absorbed. However, if the combination is
transformed into the injectable form, naloxone then acts as an opioid receptor antagonist.
Buprenorphine is metabolized through N-dealkylation to norbuprenorphine through cytochrome P450
3A4. Both parent and metabolite then undergo glucuronidation. Norbuprenorphine is an active
metabolite possessing one-fifth of the potency of its parent. The glucuronide metabolites are inactive.(1)
The primary clinical utility of quantification of buprenorphine in urine is to identify patients that have
strayed from opioid dependence therapy.
Useful For: Monitoring of compliance of buprenorphine therapy Detection and confirmation of the
illicit use of buprenorphine
Interpretation: The presence of buprenorphine above 5.0 ng/mL or norbuprenorphine above 2.5
ng/mL is a strong indicator that the patient has used buprenorphine.
Reference Values:
Negative
Cutoff concentrations:
Buprenorphine: 5.0 ng/mL
Norbuprenorphine: 2.5 ng/mL
Useful For: Monitoring of compliance utilizing buprenorphine Detection and confirmation of the illicit
use of buprenorphine
Interpretation: The presence of buprenorphine above 5.0 ng/mL or norbuprenorphine above 2.5
ng/mL is a strong indicator that the patient has used buprenorphine.
Reference Values:
Negative
Cutoff concentrations:
Buprenorphine: 5.0 ng/mL
Norbuprenorphine: 2.5 ng/mL
Reference Values:
Drug Screening Threshold Confirmation Threshold
Norbuprenorphine (Metabolite)
Reference Values:
Negative
Screening cutoff concentration:
Buprenorphine: 5 ng/mL
Reference Values:
Negative
Screening cutoff concentration:
Buprenorphine: 5 ng/mL
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 351
Clinical References: 1. Elkader A, Spuroule B: Buprenorphine clinical pharmacokinetics in the
treatment of opioid dependence. Clin Pharmacokinet 2005;44(7):661-680
Reference Values:
Reporting Limit:
Bupropion: 5.0 ng/mL
Hydroxybupropion: 50 ng/mL
Expected serum buspirone concentrations in patients taking recommended daily dosages: up to 10.00
ng/mL.
Useful For: Guiding dosage adjustments to achieve complete bone marrow ablation while minimizing
dose-dependent toxicity
Interpretation: This test should only be ordered when the following criteria are met: -Busulfan dosing
protocol must be intravenous (IV) administration of 8 mg/kg doses every 6 hours over 4 days, for a total
of 16 doses -Specimens must be drawn as described below: - 1 specimen drawn immediately after
termination of a 2-hour IV infusion of busulfan - 1 specimen drawn 1 hour after the infusion is terminated
- 1 specimen drawn 2 hours after the infusion is terminated - 1 specimen drawn 4 hours after the infusion
is terminated These results will be used to calculate a 6-hour area under the curve (AUC). If a different
dosing or specimen collection protocol is used, or if different calculations are required, please contact the
Laboratory Director. The optimal result for AUC (6 hour) derived from this pharmacokinetic (PK)
evaluation of IV busulfan is 1,100 (mcmol/L)(min). AUC results >1,500 (mcmol/L)(min) are associated
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with hepatic veno-occlusive disease. A dose reduction should be considered before the next busulfan
infusion. AUC results <900 (mcmol/L)(min) are consistent with incomplete bone marrow ablation. A
dose increase should be considered before the next busulfan infusion. Clearance of busulfan in patients
with normal renal function is usually in the range of 2.1 to 3.5 (mL/min)/kg. Elevated AUC is typically
associated with clearance <2.5 (mL/min)/kg, most frequently due to diminished activity of glutathione
S-transferase A1-1 activity.(3)
Reference Values:
AREA UNDER THE CURVE
900-1,500 (mcmol/L)(min)
CLEARANCE
2.1-3.5 (mL/minute)/kg
Clinical References: 1. Santos GW, Tutschka PJ, Brookmeyer R, et al: Marrow transplantation for
acute nonlymphocytic leukemia after treatment with busulfan and cyclophosphamide. N Engl J Med
1983 December 1;309(22):1347-1353 2. Slattery JT, Sanders JE, Buckner CD, et al: Graft-rejection and
toxicity following bone marrow transplantation in relation to busulfan pharmacokinetics. Bone Marrow
Transpl 1995 July;16(1):31-42 3. Slattery JT, Risler LJ: Therapeutic monitoring of busulfan in
hematopoietic stem cell transplantation. Ther Drug Monit 1998 October;20(5):543-549 4. Czerwinski
M, Gibbs M, Slattery JT: Busulfan conjugation by glutathione S-transferases alpha, mu, and pi. Drug
Metab Dispos 1996 September;24(9):1015-1019
Clinical References: 1. Disposition of Toxic Drugs and Chemicals in Man. Seventh edition.
Edited by RC Baselt. Foster City, CA, Biomedical Publications, 2004, p 1254 2. Teitz Textbook of
Clinical Chemistry and Molecular Diagnostics. Fourth edition. Edited by CA Burtis, ER Ashwood, DE
Bruns. St. Louis, MO, Elsevier
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neither hepatic nor significant peripheral degradation, but is mainly removed by the kidneys. As a result,
C-peptide has a longer half-life than insulin (30-35 minutes versus 5-10 minutes) and the molar ratio of
circulating insulin to circulating C-peptide is generally <1, despite equimolar secretion. Until recently,
C-peptide was thought to have no physiological function, but it now appears that there may be specific
C-peptide cell-surface receptors (most likely belonging to the super-family of G-protein coupled
receptors), which influence endothelial responsiveness and skeletal and renal blood flow. In most
disease conditions associated with abnormal serum insulin levels, the changes in serum C-peptide levels
parallel insulin-related alterations (insulin to C-peptide molar ratio < or =1). Both serum C-peptide and
serum insulin levels are elevated in renal failure and in disease states that lead to augmented primary
endogenous insulin secretion (eg, insulinoma, sulfonylurea intoxication). Both also may be raised in any
disease states that cause secondary increases in endogenous insulin secretion mediated through insulin
resistance, primarily obesity, glucose intolerance, and early type 2 diabetes mellitus (DM), as well as
endocrine disorders associated with hypersecretion of insulin-antagonistic hormones (eg, Cushing
syndrome, acromegaly). Failing insulin secretion in type 1 DM and longstanding type 2 DM is
associated with corresponding reductions in serum C-peptide levels. Discordant serum insulin and
serum C-peptide abnormalities are mainly observed in 2 situations: exogenous insulin administration
and in the presence of anti-insulin autoantibodies. Factitious hypoglycemia due to surreptitious insulin
administration results in appropriate suppression of endogenous insulin and C-peptide secretion. At the
same time, the peripherally administered insulin bypasses the hepatic first-pass metabolism. In these
situations, insulin levels are elevated and C-peptide levels are decreased. In patients with insulin
antibodies, insulin levels are increased because of the prolonged half-life of autoantibody-bound insulin.
Some patients with anti-idiotypic anti-insulin autoantibodies experience episodic hypoglycemia caused
by displacement of autoantibody-bound insulin.
Interpretation: To compare insulin and C-peptide concentrations (ie, insulin to C-peptide ratio):
-Convert insulin to pmol/L: insulin concentration in mcIU/mL x 6.945 = insulin concentration in pmol/L
-Convert C-peptide to pmol/L: C-peptide concentration in ng/mL x 331 = C-peptide concentration in
pmol/L Factitious hypoglycemia due to surreptitious insulin administration results in elevated serum
insulin levels and low or undetectable C-peptide levels, with a clear reversal of the physiological molar
insulin to C-peptide ratio (< or =1) to an insulin to C-peptide ratio of >1. By contrast, insulin and
C-peptide levels are both elevated in insulinoma and the insulin to C-peptide molar ratio is < or =1.
Sulfonylurea ingestion also is associated with preservation of the insulin to C-peptide molar ratio of < or
=1. In patients with insulin autoantibodies, the insulin to C-peptide ratio may be reversed to >1, because
of the prolonged half-life of autoantibody-bound insulin. Dynamic testing may be necessary in the workup
of hypoglycemia; the C-peptide suppression test is most commonly employed. C-peptide levels are
measured following induction of hypoglycemia through exogenous insulin administration. The test relies
on the demonstration of the lack of suppression of serum C-peptide levels within 2 hours following
insulin-induced hypoglycemia in patients with insulinoma. Reference intervals have not been formally
verified in-house for pediatric patients. The published literature indicates that reference intervals for adult
and pediatric patients are comparable.
Reference Values:
1.1-4.4 ng/mL
Reference intervals have not been formally verified in-house for pediatric patients. The published
literature indicates that reference intervals for adult and pediatric patients are comparable.
Clinical References: 1. Service FJ, O'Brien PC, Kao PC, Young WF Jr: C-peptide suppression test:
effects of gender, age, and body mass index; implications for the diagnosis of insulinoma. J Clin
Endocrinol Metab 1992;74:204-210 2. Lebowitz MR, Blumenthal SA: The molar ratio of insulin to
C-peptide. An aid to the diagnosis of hypoglycemia due to surreptitious (or inadvertent) insulin
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 354
administration. Arch Int Med 1993 Mar 8;153(5):650-655 3. Service FJ: Hypoglycemic disorders. N Engl
J Med 1995 Apr 27;332(17):1144-1152 4. Wahren J, Ekberg K, Johansson J, et al: Role of C-peptide in
human physiology. Am J Physiol Endocrinol Metab 2000 May;278(5):E759-E768 5. Young DS, Huth EJ:
SI Units for Clinical Measurement. First edition. American College of Physicians. Philadelphia, PA, 1998
Clinical References: 1. van Aalten SM, Verheij J, Terkivatan T, et al: Validation of a liver
adenoma classification system in a tertiary referral centre: implications for clinical practice. J Hepatol
2011;55(1):120-125 2. Bioulac-Sage P, Cubel G, Balabaud C, et al: Revisiting the pathology of resected
benign hepatocellular nodules using new immunohistochemical markers. Semin Liver Dis 2011;
31(1):91-103 3. Bioulac-Sage P, Rebouissou S, Thomas C, et al: Hepatocellular adenoma subype
classification using molecular markers and immunohistochemistry. Hepatology 2007; 46(3):740-748
Useful For: Detecting systemic inflammatory processes Detecting infection and assessing response
to antibiotic treatment of bacterial infections Differentiating between active and inactive disease forms
with concurrent infection HSCRP / C-Reactive Protein, High Sensitivity, Serum is the appropriate
C-reactive protein test to order to assess risk of cardiovascular disease or events
Interpretation: In normal healthy individuals, C-reactive protein (CRP) is a trace protein (<8 mg/L).
Elevated values are consistent with an acute inflammatory process. After onset of an acute phase
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response, the serum CRP concentration rises rapidly (within 6-12 hours and peaks at 24-48 hours) and
extensively. Concentrations above 100 mg/L are associated with severe stimuli such as major trauma
and severe infection (sepsis).
Reference Values:
< or =8.0 mg/L
Clinical References: Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Edited by
CA Burtis, ER Ashwood, DE Bruns. St. Louis, MO. Elsevier Saunders, 2012
Useful For: Assessment of risk of developing myocardial infarction in patients presenting with acute
coronary syndromes Assessment of risk of developing cardiovascular disease or ischemic events in
individuals who do not manifest disease at present
Reference Values:
Lower risk: <2.0 mg/L
Higher risk: > or =2.0 mg/L
Acute inflammation: >10.0 mg/L
Clinical References: 1. Ridker PM, Danielson E, Fonseca FA, et al: Reduction in C-reactive protein
and LDL-cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of
the JUPITER trial. Lancet 2009;373:1175-1182 2. European Association for Cardiovascular Prevention
and Rehabilitation, Reiner Z, Catapano AL, et al: ESC/EAS Guidelines for the management of
dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of
Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J 2011;32:1769-1818 3.
Goff DC, Lloyd-Jones DM, Bennett G, et al: 2013 ACC/AHA Guideline on the Assessment of
Cardiovascular Risk. Circulation 2014;129:S49-S73 4. Jacobson TA, Ito MK, Maki KC, et al: National
Lipid Association recommendations for patient-centered management of dyslipidemia: part 1 - executive
summary. J Clin Lipidol 2014;8:473-488
Useful For: Diagnosis of hereditary angioedema Monitoring levels of C1 esterase inhibitor in response
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 356
to therapy
Interpretation: Abnormally low results are consistent with a heterozygous C1 esterase inhibitor
deficiency and hereditary angioedema. Fifteen percent of hereditary angioedema patients have a normal
or elevated level but nonfunctional C1 esterase inhibitor protein. Detection of these patients requires a
functional measurement of C1 esterase inhibitor; FC1EQ / C1 Esterase Inhibitor, Functional Assay,
Serum. Measurement of C1q antigen levels; C1Q / Complement C1q, Serum, is key to the differential
diagnoses of acquired or hereditary angioedema. Those patients with the hereditary form of the disease
will have normal levels of C1q, while those with the acquired form of the disease will have low levels.
Studies in children show that adult levels of C1 inhibitor are reached by 6 months of age.
Reference Values:
19-37 mg/dL
Useful For: Diagnosing hereditary angioedema and for monitoring response to therapy
Interpretation: Hereditary angioedema (HAE) can be definitely diagnosed by laboratory tests
demonstrating a marked reduction in C1 inhibitor (C1-INH) antigen or abnormally low functional
C1-INH levels in a patient's plasma or serum that has normal or elevated antigen. Nonfunctional results
are consistent with HAE. Patients with current attacks will also have low C2 and C4 levels due to C1
activation and complement consumption. Patients with acquired C1-INH deficiency have a low C1q in
addition to low C1-INH.
Reference Values:
>67% normal (normal)
41-67% normal (equivocal)
<41% normal (abnormal)
Less than 4 ugE/mL is considered negative for circulating complement binding immune complexes.
Circulating immune complexes may be found without any evident pathology and positive results do not
necessarily implicate the immune complex in a disease process.
Useful For: Diagnosis of first component of complement (C1) deficiency Investigation of a patient
with an absent total complement (CH50) level
Interpretation: Low levels of complement may be due to inherited deficiencies, acquired deficiencies,
or due to complement consumption (eg, as a consequence of infectious or autoimmune processes). The
measurement of C1q activity is an indicator of the amount of first component of complement (C1)
present. Absent C1q levels in the presence of normal C3 and C4 values are consistent with a C1
deficiency. Low C1q levels in the presence of low C4 but normal C3 may indicate the presence of an
acquired inhibitor (autoantibody) to C1 esterase inhibitor.
Reference Values:
34-63 U/mL
Clinical References:
Useful For: The investigation of a patient with a low (absent) hemolytic complement (CH50)
Interpretation: Absent (or low) C2 levels in the presence of normal C3 and C4 values are consistent
with a C2 deficiency. Low C2 levels in the presence of low C3 and C4 values are consistent with a
complement-consumptive process. Low C2 and C4 values, in the presence of normal values for C3 is
suggestive of C1 esterase inhibitor deficiency.
Reference Values:
25-47 U/mL
Clinical References: 1. Gaither TA, Frank MM: Complement. In Clinical Diagnosis and
Management by Laboratory Methods. 17th edition. Edited by JB Henry. Philadelphia, PA, WB
Saunders Company, 1984, pp 879-892 2. Agnello V: Complement deficiency states. Medicine
1978;57:1-23 3. Buckley D, Barnes L: Childhood subacute cutaneous lupus erythematosus associated
with homozygous complement 2 deficiency. Pediatr Dermatol 1995;12:327-330
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 359
C2 C2 Complement, Functional, with Reflex, Serum
81835 Clinical Information: The classic pathway of the complement system is composed of a series of
proteins that are activated in response to the presence of immune complexes. This activation process
results in the formation of the lytic membrane attack complex, as well as the generation of activation
peptides that are chemotactic for neutrophils and that bind to immune complexes and complement
receptors. The absence of early components (C1, C2, C4) of the complement cascade results in the
inability of immune complexes to activate the cascade. Patients with deficiencies of the early complement
proteins are unable to generate lytic activity or to clear immune complexes. These patients have increased
susceptibility to infections with encapsulated microorganisms. They may also have symptoms that suggest
autoimmune disease, and complement deficiency may be an etiologic factor in the development of
autoimmune disease. Although rare, C2 deficiency is the most common inherited complement deficiency.
Homozygous C2 deficiency has an estimated prevalence ranging from 1 in 10,000 to 1 in 40,000 (the
prevalence of heterozygotes is 1 in 100 to 1 in 50). Half of the homozygous patients are clinically normal.
However, discoid lupus erythematosus or systemic lupus erythematosus (SLE) occurs in approximately
one-third of patients with homozygous C2 deficiency. Patients with SLE and a C2 deficiency frequently
have a normal anti-ds DNA titer. Clinically, many have lupus-like skin lesions and photosensitivity, but
immunofluorescence studies may fail to demonstrate immunoglobulin or complement along the
epidermal-dermal junction. Other diseases reported to be associated with C2 deficiency include
dermatomyositis, glomerulonephritis, vasculitis, atrophodema, cold urticaria, inflammatory bowel disease,
and recurrent infections. The laboratory findings that suggest C2 deficiency include a hemolytic
complement (CH50) of nearly zero, with normal values for C3 and C4.
Useful For: The investigation of a patient with a low (absent) hemolytic complement (CH50)
Interpretation: Low levels of complement may be due to inherited deficiencies, acquired deficiencies,
or due to complement consumption (eg, as a consequence of infectious or autoimmune processes). Absent
(or low) C2 levels in the presence of normal C3 and C4 values are consistent with a C2 deficiency. Low
C2 levels in the presence of low C3 and C4 values are consistent with a complement-consumptive
process. Low C2 and C4 values, in the presence of normal values for C3 is suggestive of C1 esterase
inhibitor deficiency.
Reference Values:
25-47 U/mL
Clinical References: 1. Gaither TA, Frank MM: Complement. In Clinical Diagnosis and
Management by Laboratory Methods. 17th edition. Edited by JB Henry. Philadelphia, PA, WB Saunders
Company, 1984, pp 879-8922 2. O'Neil KM: Complement deficiency. Clin Rev Allergy Immunol
2000;19:83-108 3. Frank MM: Complement deficiencies. Pediatr Clin North Am 2000;47:1339-1354 4.
Agnello V: Complement deficiency states. Medicine 1978;57:1-23 5. Buckley D, Barnes L: Childhood
subacute cutaneous lupus erythematosus associated with homozygous complement 2 deficiency. Pediatr
Dermatol 1995;12:327-330
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 360
C3 is at the entry point for all 3 activation pathways to activate the MAC. C3 deficiency may result in
pneumococcal and neisserial infections as well as autoimmune diseases such as glomerulonephritis.
Complement levels can be detected by antigen assays that quantitate the amount of the protein (C3 /
Complement C3, Serum). For most of the complement proteins, a small number of cases have been
described in which the protein is present but is non functional. These rare cases require a functional assay
to detect the deficiency.
Useful For: Diagnosis of C3 deficiency Investigation of a patient with undetectable total complement
(CH50) level
Reference Values:
21-50 U/mL
Clinical References: 1. Davis ML, Austin C, Messmer BL, et al: IFCC-standardization pediatric
reference intervals for 10 serum proteins using the Beckman Array 360 system. Clin Biochem
1996;29(5):489-492 2. Gaither TA, Frank MM: Complement. In Clinical Diagnosis and Management
by Laboratory Methods. 17th edition. Edited by JB Henry. Philadelphia, WB Saunders Company, 1984,
pp 879-892 3. O'Neil KM: Complement deficiency. Clin Rev Allergy Immunol 2000;19:83-108 4.
Frank MM: Complement deficiencies. Pediatr Clin North Am 2000;47(6):1339-1354
Useful For: Evaluation of patients with abnormal newborn screens showing elevations of
iso-/butyrylcarnitine (C4) to aid in the differential diagnosis of short-chain acyl-CoA dehydrogenase
and isobutyryl-CoA dehydrogenase deficiencies
Reference Values:
<3.00 millimoles/mole creatinine
Clinical References: 1. Oglesbee D, Vockley J, Ensenauer RE, et al: Ten cases of isobutyryl-CoA
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 361
dehydrogenase (IBDH) deficiency detected by newborn screening. JIMD 2005;28(Suppl 1):13 2.
Oglesbee D, He M, Majumder N, et al: Development of a newborn screening follow-up algorithm for
the diagnosis of isobutyryl-CoA dehydrogenase deficiency. Genet Med 2007;9:108-116
Interpretation: Low levels of complement may be due to inherited deficiencies, acquired deficiencies,
or due to complement consumption (eg, as a consequence of infectious or autoimmune processes). Absent
C4 levels in the presence of normal C3 and C2 values are consistent with a C4 deficiency. Normal results
indicate both normal C4 protein levels and normal functional activity. In hereditary angioedema, a
disorder caused by C1 esterase inhibitor deficiency, absent or low C4 and C2 values are seen in the
presence of normal C3 (due to activation and consumption of C4 and C2).
Reference Values:
22-45 U/mL
Clinical References: 1. Davis ML, Austin C, Messmer BL, et al: IFCC-standardization pediatric
reference intervals for 10 serum proteins using the Beckman Array 360 system. Clin Biochem
1996;29(5):489-492 2. Gaither TA, Frank MM: Complement. In Clinical Diagnosis and Management by
Laboratory Methods. 17th edition. Edited by JB Henry. Philadelphia, WB Saunders Company, 1984, pp
879-892 3. O'Neil KM: Complement deficiency. Clin Rev in Allergy Immunol 2000;19:83-108 4. Frank
MM: Complement deficiencies. Pediatr Clin North Am 2000;47:1339-1354
Useful For: Diagnosis of C5 deficiency Investigation of a patient with an absent total complement
(CH50) level
Reference Values:
10.6-26.3 mg/dL
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deficiency. Absent C5 levels in the presence of low C3 and C4 values suggest complement
consumption. Normal results indicate both normal C5 protein levels and normal functional activity.
Reference Values:
29-53 U/mL
Useful For: Evaluation of patients with an abnormal newborn screen showing elevations of C5-DC
Diagnosis of glutaric aciduria type 1 deficiency
Interpretation: Elevated excretion of C5-DC is a specific biochemical marker of glutaric aciduria type
1 that is elevated in affected patients, apparently even in low excretors or those affected individuals with
normal levels of glutaric acid in urine.
Reference Values:
<1.54 millimoles/mole creatinine
Clinical References: 1. Tortorelli S, Hahn SH, Cowan TM, et al: The urinary excretion of
glutarylcarnitine is an informative tool in the biochemical diagnosis of glutaric acidemia type I. Mol
Genet Metab 2005;84:137-143 2. Kolker S, Christensen E, Leonar JV, et al: Diagnosis and management
of glutaric aciduria type I-revised recommendations. J Inherit Metab Dis 2011:34:677-694
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 364
typically excrete larger amounts of C5-OH in urine compared to patients with the other diagnoses. The
American College of Medical Genetics (ACMG) newborn screening work group published diagnostic
algorithms for the follow-up of infants who had positive newborn screening results. For more information,
see http://www.acmg.net.
Useful For: Evaluation of patients with an abnormal newborn screen showing elevations of
3-hydroxyisovaleryl-/2-methyl-3-hydroxybutyryl-carnitine (C5-OH)
Interpretation: Preliminary data showed that an elevated excretion in urine and concentration in
plasma of 3-hydroxyisovaleryl-/2-methyl-3-hydroxy acylcarnitine (C5-OH) can be the only biochemical
abnormalities in patients with 3-methylcrotonylglycinuria. Contact Mayo Medical Laboratories for
assistance in test interpretation and additional testing options.
Reference Values:
<2.93 millimoles/mole creatinine
Clinical References: Wolfe LA, Finegold DN, Vockley J, et al: Potential misdiagnosis of
3-methylcrotonyl-coenzyme A carboxylase deficiency associated with absent or trace urinary
3-methylcrotonylglycine. Pediatrics 2007 Nov;120(5):e1335-1340
Reference Values:
32-57 U/mL
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C7FX C7 Complement, Functional, Serum
81064 Clinical Information: Complement proteins are components of the innate immune system. There are
3 pathways to complement activation: 1) the classic pathway, 2) the alternative (or properdin) pathway,
and 3) the lectin activation (mannan-binding protein; MBP) pathway. The classic pathway of the
complement system is composed of a series of proteins that are activated in response to the presence of
immune complexes. The activation process results in the generation of peptides that are chemotactic for
neutrophils and that bind to immune complexes and complement receptors. The end result of the
complement activation cascade is the formation of the lytic membrane attack complex (MAC). Patients
with deficiencies of the late complement proteins (C5, C6, C7, C8, and C9) are unable to form the MAC,
and may have increased susceptibility to neisserial infections. The majority of cases of C7 deficiency have
neisserial infections, but cases of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA),
scleroderma, and pyoderma gangrenosum have been reported. The pathogenesis of the rheumatic disease
is not clear. Complement levels can be detected by antigen assays that quantitate the amount of the
protein. For most of the complement proteins, a small number of cases have been described in which the
protein is present but is non-functional. These rare cases require a functional assay to detect the
deficiency.
Interpretation: Low levels of complement may be due to inherited deficiencies, acquired deficiencies,
or due to complement consumption (eg, as a consequence of infectious or autoimmune processes). Absent
C7 levels in the presence of normal C3 and C4 values are consistent with a C7 deficiency. Absent C7
levels in the presence of low C3 and C4 values suggest complement consumption.
Reference Values:
36-60 U/mL
Useful For: Diagnosis of C8 deficiency Investigation of a patient with an undetectable total hemolytic
complement (CH50) level
Interpretation: Low levels of complement may be due to inherited deficiencies, acquired deficiencies,
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 366
or due to complement consumption (eg, as a consequence of infectious or autoimmune processes). Absent
C8 levels in the presence of normal C3 and C4 values are consistent with a C8 deficiency. Absent C8
levels in the presence of low C3 and C4 values suggests complement consumption. Normal results
indicate both normal C8 protein levels and normal functional activity.
Reference Values:
33-58 U/mL
Useful For: Diagnosis of C9 deficiency Investigation of a patient with a low total (hemolytic)
complement (CH50) level
Reference Values:
37-61 U/mL
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 367
by Laboratory Methods. 17th edition. Edited by JB Henry. Philadelphia, WB Saunders Company, 1984,
pp 879-892 5. O'Neil KM: Complement deficiency. Clin Rev Allergy Immunol 2000;19:83-108 6.
Frank MM: Complement deficiencies. Pediatr Clin North Am 2000;47(6):1339-1354
*Alleles greater than 30 repeats are outside the reportable range for this assay and are detected using the
companion Southern blot assay. There is not enough information at this time to determine if 30 repeats is
the cutoff for pathogenicity.
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical utility
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of food-specific IgG tests has not been established. These tests can be used in special clinical situations to
select foods for evaluation by diet elimination and challenge in patients who have food-related
complaints. It should be recognized that the presence of food-specific IgG alone cannot be taken as
evidence of food allergy and only indicates immunologic sensitization by the food allergen in question.
This test should only be ordered by physicians who recognize the limitations of the test.
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
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immune response to allergen(s) that may be associated with allergic disease. The allergens chosen for
testing often depend upon the age of the patient, history of allergen exposure, season of the year, and
clinical manifestations. In individuals predisposed to develop allergic disease(s), the sequence of
sensitization and clinical manifestations proceed as follows: eczema and respiratory disease (rhinitis and
bronchospasm) in infants and children less than 5 years due to food sensitivity (milk, egg, soy, and
wheat proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens responsible for anaphylaxis, to confirm sensitization to particular allergens prior to
beginning immunotherapy, and to investigate the specificity of allergic reactions to insect venom
allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Reference Values:
0.0-4.9 mcg/L
Reference values apply to all ages.
Clinical References: 1. Moreau T, Lellouch J, Juguet B, et al: Blood cadmium levels in a general
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 370
male population with special reference to smoking. Arch Environ Health 1983;38:163-167 2.
Occupational Safety and Health Administration, US Department of Labor: Cadmium Exposure
Evaluation. Updated 9/2/2008. Available from URL:osha.gov/SLTC/cadmium/evaluation.html
Reference Values:
<3.0 mcg/g
Clinical References: 1. deBurbure C, Buchet J-P, Leroyer A, et al: Renal and Neurologic Effects
of Cadmium, Lead, Mercury, and Arsenic in Children: Evidence of Early Effects and Multiple
Interactions at Environmental Exposure Levels. Environ Health Perspect 2006;114:584590 2. Schulz
C, Angerer J, Ewers U, et al: Revised and new reference values for environmental pollutants in urine or
blood of children in Germany derived from the German Environmental Survey on Children
2003-2006(GerESIV). Int. J. Hyg. Environ. Health 2009;212:637647 3. Occupational Safety and
Health Administration, US Department of Labor: Cadmium Exposure Evaluation. Updated 9/2/2008.
Available from URL:osha.gov/SLTC/cadmium/evaluation.html
Clinical References: 1. deBurbure C, Buchet J-P, Leroyer A, et al: Renal and Neurologic Effects of
Cadmium, Lead, Mercury, and Arsenic in Children: Evidence of Early Effects and Multiple Interactions at
Environmental Exposure Levels. Environ Health Perspect 2006;114:584-590 2. Schulz C, Angerer J,
Ewers U, et al: Revised and new reference values for environmental pollutants in urine or blood of
children in Germany derived from the German Environmental Survey on Children 2003-2006(GerESIV)
Int J Hyg Environ Health 2009;212:637-647 3. Occupational Safety and Health Administration, US
Department of Labor: Cadmium Exposure Evaluation. Updated 9/2/2008. Available from URL:
osha.gov/SLTC/cadmium/evaluation.html
Reference Values:
0.0-4.9 ng/mL
Reference values apply to all ages.
Clinical References: Moreau T, Lellouch J, Juguet B, et al: Blood cadmium levels in a general
population with special reference to smoking. Arch Environ Health 1983;38:163-167
Clinical References: 1. deBurbure C, Buchet J-P, Leroyer A, et al: Renal and Neurologic Effects
of Cadmium, Lead, Mercury, and Arsenic in Children: Evidence of Early Effects and Multiple
Interactions at Environmental Exposure Levels. Environ Health Perspect 2006;114:584-590 2. Schulz
C, Angerer J, Ewers U, et al: Revised and new reference values for environmental pollutants in urine or
blood of children in Germany derived from the German Environmental Survey on Children
2003-2006(GerESIV). Int J Hyg Environ Health 2009;212:637-647 3. Occupational Safety and Health
Administration, US Department of Labor: Cadmium Exposure Evaluation. Updated 9/2/2008. Available
from URL: osha.gov/SLTC/cadmium/evaluation.html
Reference Values:
Therapeutic: 8.0-20.0 mcg/mL
Critical value: > or =30.0 mcg/mL
Clinical References: Ou CN, Frawley VL: Concurrent measurement of theophylline and caffeine
in neonates by an interference-free liquid-chromatographic method. Clin Chem 1983;29:1934-1936
1-11m <10 - 37
Androstenedione gradually decreases during the first six months to prepubertal levels.
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Prepubertal Children <10-17
Adult Males 44 - 186
Adult Females 28 - 230
Females Postmenopausal <10-93
Cortisol
Units: ug/dL
Age Range
Premature (26-28w) Day 4 1.0 - 11
Premature (31-35w) Day 4 2.5 - 9.1
Full Term Day 3 1.7 - 14
Full Term Day 7 2.0 - 11
31d - 11m 2.8 - 23
12m - 15y (8:00 AM) 3 .0 - 21
Adults
8:00 AM 8.0 - 19
4:00 PM 4.0 - 11
Deoxycorticosterone (DOC)
Units: ng/dL
Age Range
Premature (26 - 28w) Day 4 20 - 105
Premature (34 - 36w) Day 4 28 - 78
Newborn: Levels are markedly elevated at birth and decrease rapidly during the first week to the
range of 7 - 49 as found in older infants.
1 - 11m 7 - 49
Prepubertal Children 2 - 34
Pubertal Children
and Adults 8:00 AM 2 - 19
Dehydroepiandrosterone (DHEA)
Units: ng/dL
Age Range
Premature (26 - 31w) 82 1484
Premature (32 - 35w) 56 1853
Full Term (2 7d) 41 1292
8d - 5m <948
6 12m <136
1-5 y <68
6-7 y <111
8-10 y <186
11-12 y <202
13-14 y <319
15-16 y 39-481
17-19 y 40-491
20-49 y 31-701
> or = 50 y 21-402
11-Desoxycortisol
Units: ng/dL
Age Range
Premature (26-28w) Day 4 110 - 1376
Premature (31-35w) Day 4 48 - 579
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Newborn Day 3 13 - 147
1 - 11m <10 - 156
Prepubertal 8:00 AM 20 - 155
Pubertal Children and
Adults 8:00 AM 12 - 158
17-OH Pregnenolone
Units: ng/dL
Age Range
Premature (26-28w) Day 4 375 - 3559
Premature (31-35w) Day 4 64 - 2380
3 Days 10 - 829
1 - 5m 36 - 763
6 - 11m 42 - 540
12 - 23m 14 - 207
24m - 5y 10 - 103
6 - 9y 10 - 186
Pubertal 44 - 235
Adults 53 - 357
Progesterone
Units: ng/dL
Males
Age Range
1-16y <10-15
Adults <10-11
Females
Age Range
1-10y <10-26
11y <10-255
12y <10-856
13y <10-693
14y <10-1204
15y <10-1076
16y <10-1294
Adult
Cycle Days Range
1-6 <10-17
7-12 <10-135
13-15 <10-1563
16-28 <10-2555
Post Menopausal <10
Note: Luteal progesterone peaked from 350 to 3750 ng/dL on days ranging from 17 to 23.
17-Alpha-Hydroxyprogesterone
Units: ng/dL
Age Range
Premature (26-28w) Day 4 124 - 841
Premature (31-35w) Day 4 26 - 568
Full-Term Day 3 <78
Males: Levels increase after the first week to peak values ranging from 40 - 200 between 30 and 60
days. Values then decline to a prepubertal value of <91 before one year.
Prepubertal <91
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Adult Males 27-199
Females
1 - 11m 13-106
Prepubertal <91
Adult Females
Follicular 15-70
Luteal 35-290
1 - 7m: Levels decrease rapidly the first week to 20 - 50, then increase to 60 - 400 between 20 - 60
days. Levels then decline to prepubertal range levels of <2.5 - 10 by seven months.
Females
Premature (26 - 28w) Day 4 5 - 16
Premature (31 - 35w) Day 4 5 - 22
Newborns 20 - 64
1 - 7m: Levels decrease during the first month to less than 10 and remain there until puberty.
Males
Tanner Stage Age (years) Male
1 <9.8 <2.5 - 10
2 9.8 - 14.5 18 - 150
3 10.7 - 15.4 100 - 320
4 11.8 - 16.2 200 - 620
5 12.8 - 17.3 350 - 970
Females
Tanner Stage Age (years) Female
1 <9.2 <2.5 - 10
2 9.2 - 13.7 7 - 28
3 10.0 - 14.4 15 - 35
4 10.7 - 15.6 13 - 32
5 11.8 - 18.6 20 - 38
Useful For: An aid in the identification of C cells of thyroid, medullary thyroid carcinomas, many
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 376
atypical laryngeal carcinoids, and other neuroendocrine tumors
Interpretation: This test includes only technical performance of the stain (no pathologist
interpretation is performed). If diagnostic consultation by a pathologist is required, order 70012 /
Pathology Consultation. The positive and negative controls are verified as showing appropriate
immunoreactivity. If a control tissue is not included on the slide, a scanned image of the relevant quality
control tissue is available upon request; contact 855-516-8404. Interpretation of this test should be
performed in the context of the patient's clinical history and other diagnostic tests by a qualified
pathologist.
Clinical References: 1. Hayashida CY, Alves VA, Kanamura CT, et al: Immuhohistochemistry of
medullary thyroid carcinoma and C-cell hyperplasia by an affinity-purified anti-human calcitonin
antiserum. Cancer 1993;72:1356-1363 2. Hirsch MS, Faquin WC, Krane JF: Thyroid transcription
factor-1, but not p53, is helpful in distinguishing moderately differentiated neuroendocrine carcinoma of
the larynx from medullary carcinoma of the thyroid. Mod Pathol 2004;17:631-636 3. Thomas RM,
Baybick JH, Eldayed AM, et al: Gastric carcinoids. An immunohistochemical and clinicopathologic
study of 104 patients. Cancer 1994;73(8):2053-2058
Reference Values:
An interpretive report will be provided.
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aspiration biopsy specimens. Thyroid 2007 Jul;17(7):635-638
Useful For: Aids in the diagnosis and follow-up of medullary thyroid carcinoma Aids in the evaluation
of multiple endocrine neoplasia type II and familial medullary thyroid carcinoma
Interpretation: Although most patients with sporadic medullary thyroid carcinoma (MTC) have high
basal serum calcitonin concentrations, 30% of those with familial MTC or multiple endocrine neoplasia
type II (MENII) have normal basal levels. In completely cured cases following surgical therapy for MTC,
serum calcitonin levels fall into the undetectable range over a variable period of several weeks.
Persistently elevated postoperative serum calcitonin levels usually indicate incomplete cure. The reasons
for this can be locoregional lymph node spread or distant metastases. In most of these cases, imaging
procedures are required for further workup. Those individuals who are then found to suffer only
locoregional spread may benefit from additional surgical procedures. However, the survival benefits
derived from such approaches are still debated. A rise in previously undetectable or very low
postoperative serum calcitonin levels is highly suggestive of disease recurrence or spread, and should
trigger further diagnostic evaluations.
Reference Values:
Pediatric
1 month: < or =34
2 months: < or =31
3 months: < or =28
4 months: < or =26
5 months: < or =24
6 months: < or =22
7 months: < or =20
8 months: < or =19.0
9 months: < or =17.0
10 months: < or =16.0
11 months: < or =15.0
12-14 months: < or =14.0
15-17 months: < or =12.0
18-20 months: < or =10.0
21-23 months: < or =9.0
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2 years: < or =8.0
3-9 years: < or =7.0
10-15 years: < or =6.0
16 years: < or =5.0
Adults
17 years and older:
Males: < or =14.3
Females: < or =7.6
Clinical References: 1. Wells SA Jr, Asa SL, Dralle H, et al: Medullary Thyroid Carcinoma:
management guidelines of the American Thyroid Association. American Thyroid Association
Guidelines Task Force 2015 Jun;25(6):567-610 2. Griebeler ML, Gharib H, Thompson GB: Medullary
thyroid carcinoma. Endocr Pract 2013 Jul-Aug;19(4):703-11 3. Richards ML: Familial syndromes
associated with thyroid cancer in the era of personalized medicine. Thyroid 2010 Jul;20(7):707-13
Useful For: Evaluation of calcium oxalate and calcium phosphate kidney stone risk, and calculation
of urinary supersaturations Evaluation of bone diseases, including osteoporosis and osteomalacia
Reference Values:
Males: <250 mg/24 hours
Females: <200 mg/24 hours
Reference values have not been established for patients <18 years and >83 years of age.
Reference values apply to 24-hour collection.
Clinical References: 1. Curhan GC, Willett WC, Speizer FE, Stampfer MJ: Twenty-four-hour
urine chemistries and the risk of kidney stones among women and men. Kidney Int 2001;59:2290-2298
2. Metz MP: Determining urinary calcium/creatinine cut-offs for the pediatric population using
published data. Ann Clin Biochem 2006;43:398-401 3. Pak CY, Britton F, Peterson R, et al:
Ambulatory evaluation of nephrolithiasis. Classification, clinical presentation and diagnostic criteria.
Am J Med 1980;69:19-30 4. Pak CY, Kaplan R, Bone H, et al: A simple test for the diagnosis of
absorptive, resorptive and renal hypercalciurias. N Engl J Med 1975;292:497-500
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CAI Calcium, Ionized, Serum
8378 Clinical Information: Ionized calcium, which accounts for 50% to 55% of total calcium, is the
physiologically active form of calcium. Low ionized calcium values are often seen in renal disease,
critically ill patients, or patients receiving rapid transfusion of citrated whole blood or blood products.
Increased serum ionized calcium concentrations may be seen with primary hyperparathyroidism, ectopic
parathyroid hormone-producing tumors, excess intake of vitamin D, or various malignancies. Nomograms
have been used to calculate ionized calcium from total calcium, albumin, and pH values. However,
calculated ionized calcium results have proven to be unsatisfactory. A Mayo study of 114 patients found
significant differences between ionized and total calcium in 26% of patients.
Useful For: Assessing calcium states during liver transplantation surgery, cardiopulmonary bypass, or
any procedure requiring rapid transfusion of whole blood in neonates and in critically ill patients
Second-order test in the evaluation of patients with abnormal calcium values
Interpretation: Serum ionized calcium concentrations 50% below normal result in severely reduced
cardiac stroke work. With moderate to severe hypocalcemia, left ventricular function may be profoundly
depressed. Ionized calcium values are higher in children and young adults. Ionized calcium values vary
inversely with pH, approximately 0.2 mg/dL per 0.1 pH unit change.
Reference Values:
Males
1-19 years: 5.1-5.9 mg/dL
> or =20 years: 4.8-5.7 mg/dL
Reference values have not been established for patients that are <12 months of age.
Females
1-17 years: 5.1-5.9 mg/dL
> or =18 years: 4.8-5.7 mg/dL
Reference values have not been established for patients that are <12 months of age.
Pediatric ranges derived for GEM method from analytic comparison to reference method in: Snell J,
Greeley C, Colaco A, et al: Pediatric reference ranges for arterial pH, whole blood electrolytes and
glucose. Clin Chem 1993;39:1173.
Useful For: Evaluation of calcium oxalate and calcium phosphate kidney stone risk, and calculation of
urinary supersaturations Evaluation of bone diseases, including osteoporosis and osteomalacia
Reference Values:
Random Calcium/Creatinine Ratio: <0.20 mg/mg
Reference values have not been established for patients <18 years and >83 years of age.
Clinical References: 1. Curhan GC, Willett WC, Speizer FE, Stampfer MJ: Twenty-four-hour
urine chemistries and the risk of kidney stones among women and men. Kidney Int 2001;59:2290-2298
2. Metz MP: Determining urinary calcium/creatinine cut-offs for the pediatric population using
published data. Ann Clin Biochem 2006;43:398-401 3. Pak CY, Britton F, Peterson R, et al:
Ambulatory evaluation of nephrolithiasis. Classification, clinical presentation and diagnostic criteria.
AM J Med 1980;69:19-30 4. Pak CY, Kaplan R, Bone H, et al: A simple test for the diagnosis of
absorptive, resorptive and renal hypercalciurias. N Engl J Med 1975;292:497-500
Useful For: The diagnosis and monitoring of a wide range of disorders including diseases of bone,
kidney, parathyroid gland, or gastrointestinal tract Calcium levels may also reflect abnormal vitamin D
or protein levels
Interpretation: Hypocalcemia: Long-term therapy must be tailored to the specific disease causing
the hypocalcemia. The therapeutic endpoint is to achieve a serum calcium level of 8.0 to 8.5 mg/dL to
prevent tetany. For symptomatic hypocalcemia, calcium may be administered intravenously.
Hypercalcemia: The level at which hypercalcemic symptoms occur varies from patient to patient.
Symptoms are common when serum calcium levels are >11.5 mg/dL, although patients may be
asymptomatic at this level. Levels >12.0 mg/dL are considered a critical value in the Mayo Health
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System. Severe hypercalcemia (>15.0 mg/dL) is a medical emergency.
Reference Values:
Males
1-14 years: 9.6-10.6 mg/dL
15-16 years: 9.5-10.5 mg/dL
17-18 years: 9.5-10.4 mg/dL
19-21 years: 9.3-10.3 mg/dL
> or =22 years: 8.9-10.1 mg/dL
Reference values have not been established for patients who are <12 months of age.
Females
1-11 years: 9.6-10.6 mg/dL
12-14 years: 9.5-10.4 mg/dL
15-18 years: 9.1-10.3 mg/dL
> or =19 years: 8.9-10.1 mg/dL
Reference values have not been established for patients who are <12 months of age.
Clinical References: 1. Ceballos KM, Nielsen GP, Selig MK, et al: Is anti-h-caldesmon useful for
distinguishing smooth muscle and myofibroblastic tumors? An immunohistochemical study. Am J Clin
Pathol 2000;114:746-753 2. Hisaoka M, Wei-Qi S, Jian W, et al: Specific but variable expression of
h-caldesmon in leiomyosarcomas: an immunohistochemical reassessment of a novel myogenic marker.
Appl Immunohistochem Mol Morphol 2001;9(4):302-308 3. Sakamoto A, Oda Y, Yamamota H, et al:
Calponin and h-caldesmon expression in atypical fibrozanthoma and superficial leiomyosarcoma.
Virchows Arch 2002;440:404-409
Reference Values:
IgG: <1:10
IgM: <1:10
Reference values apply to all ages.
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and sex, as well as occupational, vocational, and recreational habits of the individuals. Once humans
have been infected, the severity of the host response may be influenced by age: serious La Crosse
infections primarily involve children, especially boys. Adult males exposed to La Crosse have high
prevalence rates of antibody but usually show no serious illness. Infection among males is primarily due
to working conditions and sports activity taking place where the vector is present.
Reference Values:
IgG: <1:10
IgM: <1:10
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gastrointestinal disorders, such as irritable bowel syndrome (IBS). When used for this differential
diagnosis, fecal calprotectin has sensitivity and specificity both of approximately 85%. However, it must
be remembered that increases in fecal calprotectin are not diagnostic for IBD, as other disorders such as
celiac disease, colorectal cancer, and gastrointestinal infections, may also be associated with neutrophilic
inflammation.
Interpretation: Calprotectin concentrations < or =50.0 mcg/g are not suggestive of an active
inflammatory process within the gastrointestinal system. For patients experiencing gastrointestinal
symptoms, consider further evaluation for functional gastrointestinal disorders. Calprotectin
concentrations between 50.1 and 120.0 mcg/g are borderline and may represent a mild inflammatory
process, such as in treated inflammatory bowel disease (IBD) or associated with NSAID or aspirin
usage. For patients with clinical symptoms suggestive of IBD, retesting in 4 to 6 weeks may be
indicated. Calprotectin concentrations > or =120.1 mcg/g are suggestive of an active inflammatory
process within the gastrointestinal system. Further diagnostic testing to determine the etiology of the
inflammation is suggested.
Reference Values:
< or =50.0 mcg/g (Normal)
50.1-120.0 mcg/g (Borderline)
> or =120.1 mcg/g (Abnormal)
Reference values apply to all ages.
Clinical References: 1. Gisbert JP, McNicholl AG, Golmollon F: Questions and answers on the
role of faecal calprotectin as a biological marker in inflammatory bowel disease. Digest Liver Dis
2009;41:56-66 2. Campeotto F, Butel MJ, Kalach N, et al: High faecal calprotectin concentrations in
newborn infants. Arch Dis Child-Fetal 2004;89:F353-F355 3. Dabritz J, Musci J, Foell D: Diagnostic
utility of faecal biomarkers in patients with irritable bowel syndrome. World J Gastroentero
2014;20(2):363-375 4. Fagerberg, UL, Loof L, Merzoug RD, et al: Fecal calprotectin levels in healthy
children studied with an improved assay. J Pediatr Gastr Nutr 2003;37:438-472
Useful For: Rapid and sensitive detection of insertion and deletion-type mutations in exon 9 of
CALR An aid in distinction between reactive thrombocytosis and/or leukocytosis versus a
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myeloproliferative neoplasm (MPN), especially essential thrombocythemia (ET) and primary
myelofibrosis (PMF), and is highly informative in cases in which JAK2 and MPL testing are negative
Especially helpful to the pathologist in those bone marrow cases with ambiguous etiology of
thrombocytosis, equivocal bone marrow morphologic findings of MPN, and/or unexplained reticulin
fibrosis An aid in prognostication of PMF and thrombosis risk assessment in ET.
Interpretation: An interpretive report will be issued. The results will be reported as 1 of the 3 states if
DNA amplification is successful (see Cautions): -Positive. A deletion/insertion-type mutation was
detected in CALR, exon 9. -Negative. No deletion or insertion was detected in CALR, exon 9. -Equivocal.
A small amplicon suspicious for a deletion/insertion type mutation was detected in CALR, exon 9.
Positive mutation status is highly suggestive of a myeloid neoplasm, but must be correlated with clinical
and other laboratory and morphologic features for definitive diagnosis. Negative mutation status does not
exclude the presence of a myeloproliferative neoplasm or other neoplastic disorders.
Reference Values:
An interpretive report will be provided
Useful For: Identifying the presence of calreticulin exon 9 frameshift mutations in myeloproliferative
neoplasms
Interpretation: This test includes only technical performance of the stain (no pathologist interpretation
is performed). If diagnostic consultation by a pathologist is required, order 70012 / Pathology
Consultation. The positive and negative controls are verified as showing appropriate immunoreactivity. If
a control tissue is not included on the slide, a scanned image of the relevant quality control tissue is
available upon request; contact 855-516-8404. Interpretation of this test should be performed in the
context of the patient's clinical history and other diagnostic tests by a qualified pathologist.
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antibody (CAL2) detects CALRETICULIN mutations in formalin-fixed and paraffin-embedded bone
marrow biopsies. Leukemia 2016 Jan;30(1):131-135 3. Klampfl T, Gisslinger H, Harutyunyan AS, etal:
Somatic mutations of Calreticulin in myeloproliferative neoplasms. N Engl J Med 2013 Dec
19;369(25):2379-2390
Useful For: Marker of mesothelial cells and Leydig cells of the testis
Interpretation: This test includes only technical performance of the stain (no pathologist
interpretation is performed). If diagnostic consultation by a pathologist is required, order 70012 /
Pathology Consultation. The positive and negative controls are verified as showing appropriate
immunoreactivity. If a control tissue is not included on the slide, a scanned image of the relevant quality
control tissue is available upon request; contact 855-516-8404. Interpretation of this test should be
performed in the context of the patient's clinical history and other diagnostic tests by a qualified
pathologist.
Clinical References: 1. Abutaily AS, Addis BJ, Roche WR: Immunohistochemistry in the
distinction between malignant mesothelioma and pulmonary adenocarcinoma: a critical evaluation of
new antibodies. J Clin Pathol 2002;55:662-668 2. Ordonez NG: The immunohistochemical diagnosis of
mesothelioma: a comparative study of epithelioid mesothelioma and lung adenocarcinoma. Am J Surg
Pathol 2003;27(8):1031-1051 3. Terracciano LM, Mhawech P, Suess K, et al: Calretinin as a marker for
cardiac myxoma. Diagnostic and histogenetic considerations. Am J Clin Pathol 2000;114:754-759
Interpretive Criteria:
<0.90 Antibody Not Detected
0.90-1.10 Equivocal
>1.10 Antibody Detected
Campylobacter jejuni is a major cause of sporadic bacterial diarrhea in the United States, with poultry
the most important source of infection. Markedly elevated levels of antibodies recognizing C. jejuni
typically indicate recent or ongoing infection, even though stool cultures may be negative. Neurological
complications may follow C. jejuni infection; approximately 30% of Guillain-Barre cases are associated
with recent C. jejuni infection. The basis of this association is apparently molecular mimicry between C.
jejuni antigens and gangliosides of neuronal cells.
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wheat proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 388
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Carrier testing for Canavan disease in individuals of Ashkenazi Jewish ancestry Prenatal
diagnosis of Canavan disease in at-risk pregnancies Confirmation of a suspected clinical diagnosis of
Canavan disease in individuals of Ashkenazi Jewish ancestry
Clinical References: 1. Gross SJ, Pletcher BA, Monaghan KG: Carrier screening individuals of
Ashkenazi Jewish descent. Genet Med 2008;10(1):54-56 2. ACOG Committee on Genetics: ACOG
Committee Opinion No. 442: Preconception and prenatal carrier screening for genetic diseases in
individuals of Eastern European Jewish descent. Obstet Gynecol 2009;Oct;114(4):950-953 3. Matalon
R: Canavan disease: diagnosis and molecular analysis. Genet Testing 1997;1:21-25
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nonmalignant conditions including: cirrhosis, hepatitis, endometriosis, first trimester pregnancy, ovarian
cysts, and pelvic inflammatory disease. Elevated levels during the menstrual cycle also have been
reported.
Useful For: Evaluating patients' response to cancer therapy, especially for ovarian carcinoma
Predicting recurrent ovarian cancer or intraperitoneal tumor
Interpretation: In monitoring studies, elevations of cancer antigen 125 (CA 125) >35 U/mL after
debulking surgery and chemotherapy indicate that residual disease is likely (>95% accuracy). However,
normal levels do not rule-out recurrence. A persistently rising CA 125 value suggests progressive
malignant disease and poor therapeutic response. Physiologic half-life of CA 125 is approximately 5 days.
In patients with advanced disease who have undergone cytoreductive surgery and are on chemotherapy, a
prolonged half-life (>20 days) may be associated with a shortened disease-free survival.
Reference Values:
<35 U/mL
Clinical References: 1. Devarbhav H, Kaese D, Williams AW, et al: Cancer antigen 125 in patients
with chronic liver disease. Mayo Clin Proc 2002;77:538-541 2. Sturgeon CM, Duffy MJ, Stenman UH, et
al: National Academy of Clinical Biochemistry laboratory medicine practice guidelines for use of tumor
markers in testicular, prostate colorectal, breast, and ovarian cancers. Clin Chem 2008 Dec;54:11-79 3.
Sugiyama T, Nishida T, Komai K, et al: Comparison of CA 125 assays with abdominopelvic computed
tomography and transvaginal ultrasound in monitoring of ovarian cancer. Int J Gynaecol Obstet
1996;54:251-256
Useful For: Managing breast cancer patients when used in conjunction with clinical information and
other diagnostic procedures Serial testing can assist in early detection of disease recurrence in previously
treated stage II and III breast cancer patients Monitoring response to therapy in metastatic breast cancer
patients
Interpretation: Increasing and decreasing values show correlation with disease progression and
regression, respectively.(1) Increasing cancer antigen 15-3 (CA 15-3) assay values in patients at risk for
breast cancer recurrence after primary therapy may be indicative of recurrent disease before it can be
detected clinically (2,3) and may be used as an indication that additional tests or procedures should be
performed.
Reference Values:
Males: <30 U/mL (use not defined)
Females: <30 U/mL
Clinical References: 1. Molina R, Zanon G, Filella X, et al: Use of serial carcinoembryonic antigen
and CA 15-3 assays in detecting relapses in breast cancer patients. Breast Cancer Res Treat
1995;36:41-48 2. Geraghty JG, Coveney EC, Sherry F, et al: CA 15-3 in patients with locoregional and
metastatic breast carcinoma. Cancer 1992;70:2831-2834 3. Kallioniemi OP, Oksa H, Aaran RK, et al:
Serum CA 15-3 assay in the diagnosis and follow-up of breast cancer. Br J Cancer 1988;58:213-215
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Interpretive Criteria:
<1.0 Antibody not detected
> or = 1.0 Antibody detected
Systemic candidiasis is often characterized by markedly elevated levels of IgG, IgA, and IgM
recognizing Candida. However, interpretation of Candida antibody levels is complicated by detection of
antibodies in 20-30% of healthy individuals, and blunted antibody responses in immuno-compromised
patients at risk for systemic candidiasis. Candida antibody results should be considered within the
context of clinical findings and results from other relevant laboratory tests, such as Candida antigen
detection and/or culture.
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FCANP Candida Antigen and Antibody Panel
91830 Reference Values:
Candida Antigen Detection
INTERPRETIVE CRITERIA:
<1:2 Antigen Not Detected
> or = 1:2 Antigen Detected
INTERPRETIVE CRITERIA:
<1.0 Antibody not detected
> or = 1.0 Antibody detected
Systemic candidiasis is often characterized by markedly elevated levels of IgG, IgA, and IgM
recognizing Candida. However, interpretation of Candida antibody levels is complicated by detection of
antibodies in 20-30% of healthy individuals, and blunted antibody responses in immuno-compromised
patients at risk for systemic candidiasis. Candida antibody results should be considered within the context
of clinical findings and results from other relevant laboratory tests, such as Candida antigen detection
and/or culture.
INTERPRETIVE CRITERIA:
<1:2 Antigen Not Detected
> or = 1:2 Antigen Detected
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CWAY Caraway, IgE
82493 Clinical Information: Clinical manifestations of immediate hypersensitivity (allergic) diseases are
caused by the release of proinflammatory mediators (histamine, leukotrienes, and prostaglandins) from
immunoglobulin E (IgE)-sensitized effector cells (mast cells and basophils) when cell-bound IgE
antibodies interact with allergen. In vitro serum testing for IgE antibodies provides an indication of the
immune response to allergen(s) that may be associated with allergic disease. The allergens chosen for
testing often depend upon the age of the patient, history of allergen exposure, season of the year, and
clinical manifestations. In individuals predisposed to develop allergic disease(s), the sequence of
sensitization and clinical manifestations proceed as follows: eczema and respiratory disease (rhinitis and
bronchospasm) in infants and children less than 5 years due to food sensitivity (milk, egg, soy, and
wheat proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
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1 to 6 cases in 10,000 persons of European ancestry who are exposed to the drug. The rate of SJS-TEN
as a result of carbamazepine exposure is about 10 times higher in some Asian countries. Clinical studies
have demonstrated associations between some human leukocyte antigen (HLA) genotypes and
drug-associated cutaneous adverse reactions. The presence of the HLA-B*15:02 allele varies throughout
Asia: 10% to 15% frequency in Chinese, 2% to 4% frequency in Southeast Asians, including Indians,
and <1% frequency in Japanese and Koreans. The HLA-A*31:01 allele, which has a prevalence of 2%
to 5% in Northern European populations, has been significantly associated with drug-associated
cutaneous adverse reactions. In the absence of HLA-A*31:01, the risk for drug-associated cutaneous
adverse reactions is 3.8%, but in the presence of this allele, the risk increases to 26%. The
FDA-approved label for carbamazepine states that the screening of patients in genetically at-risk
populations (ie, patients of Asian descent) for the presence of the HLA-B*15:02 allele should be carried
out prior to initiating treatment with carbamazepine. The FDA-approved label also notes the association
of HLA-A*31:01 allele with drug-associated cutaneous adverse reactions regardless of ethnicity but
does not specifically mandate screening of patients. For patients who are HLA-B*15:02 and
HLA-A*31:01 positive, oxcarbazepine, phenytoin, fosphenytoin, eslicarbazepine acetate, and
lamotrigine may also be associated with drug-associated cutaneous adverse reactions so these
medications may need to be avoided as well.
Useful For: Identifying individuals with increased risk of risk of carbamazepine-associated cutaneous
adverse reactions Identifying individuals who may be at increased risk of cutaneous adverse reactions
when treated with alternative medications to carbamazepine including phenytoin, fosphenytoin,
oxcarbazepine, eslicarbazepine acetate, and lamotrigine
Interpretation: The presence of the HLA-B*15:02 and/or HLA-A*31:01 allele confers increased risk
for hypersensitivity to carbamazepine.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. 1. Leckband SG, Kelsoe JR, Dunnenberger HM, et al: Clinical
Pharmacogenetics Implementation Consortium guideline for HLA-B genotype and carbamazepine dosing.
Clin Pharmacol Ther 2013;94(3):324-328 2. 2. Caudle KE, Rettie Ae, Whirl-Carrillo M, et al: Clinical
pharmacogenetics implementation consortium guidelines for CYP2C9 and HLA-B genotypes and
phenytoin dosing. Clin Pharacol Ther. 2014;96(5):542-8. 3. 3. McCormack M, Alfirevic A, Bourgeois S,
et al: HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans. N Engl J Med
2011;364:1134-1143 4. 4. Amstutz U, Shear NH, Rieder MJ, et al: Recommendations for HLA-B*15:02
and HLA-A*31:01 genetic testing to reduce the risk of carbamazepine-induced hypersensitivity reactions.
Epilepsia 2014;55:496-506
Interpretation: The presence of the HLA-B*15:02 and/or HLA-A*31:01 allele confers increased
risk for hypersensitivity to carbamazepine. For additional information regarding pharmacogenomic
genes and their associated drugs, please see the Pharmacogenomic Associations Tables in Special
Instructions. This resource also includes information regarding enzyme inhibitors and inducers, as well
as potential alternate drug choices.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. 1. Leckband SG, Kelsoe JR, Dunnenberger HM, et al: Clinical
Pharmacogenetics Implementation Consortium guideline for HLA-B genotype and carbamazepine
dosing. Clin Pharmacol Ther 2013;94(3):324-328 2. 2. Caudle KE, Rettie Ae, Whirl-Carrillo M, et al:
Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and HLA-B genotypes
and phenytoin dosing. Clin Pharacol Ther. 2014;96(5):542-8. 3. 3. McCormack M, Alfirevic A,
Bourgeois S, et al: HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans.
N Engl J Med 2011;364:1134-1143 4. 4. Amstutz U, Shear NH, Rieder MJ, et al: Recommendations for
HLA-B*15:02 and HLA-A*31:01 genetic testing to reduce the risk of carbamazepine-induced
hypersensitivity reactions. Epilepsia 2014;55:496-506
Useful For: Monitoring patients exhibiting symptoms of carbamazepine toxicity whose serum
carbamazepine concentration is within the therapeutic range, but who may be producing significant
levels of the active metabolite epoxide
Reference Values:
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CARBAMAZEPINE, TOTAL
Therapeutic: 4.0-12.0 mcg/mL
Critical value: > or =15.0 mcg/mL
CARBAMAZEPINE-10,11-EPOXIDE
Therapeutic: 0.4-4.0 mcg/mL
Toxic concentration: > or =8.0 mcg/mL
CARBAMAZEPINE, FREE
Therapeutic: 1.0-3.0 mcg/mL
Critical value: > or =4.0 mcg/mL
Clinical References: 1. Theodore WH, Narang PK, Holmes MD, et al: Carbamazepine and its
epoxide: relation of plasma levels to toxicity and seizure control. Ann Neurol 1989;25:194-196 2. Tomson
T, Almkvist O, Nilsson BY, et al: Carbamazepine-10, 11-epoxide in epilepsy. A pilot study. Arch Neurol
1990;47:888-892 3. McKauge L, Tyrer JH, Eadie MI: Factors influencing simultaneous concentrations of
carbamazepine and its epoxide in plasma. Ther Drug Monit 1981;3:63-70 4. Brodie MJ, Forrest G,
Rapeport WG: Carbamazepine-10,11-epoxide concentrations in epileptics of carbamazepine alone and in
combination with other anticonvulsants. Br J Clin Pharmacol 1983;16:747-749 5. Shoeman JF, Elyas AA,
Brett EM, Lascelles PT: Correlation between plasma carbamazepine-10,11-epoxide concentration and
drug side-effects in children with epilepsy. Dev Med Child Neurol 1984;26:756-764
Useful For: Monitoring carbamazepine (free and total) therapy in uremic patients
Interpretation: In patients with normal renal function, optimal response is often associated with free
(unbound) carbamazepine levels >1.0 mcg/mL, and toxicity may occur when the free carbamazepine is >
or =4.0 mcg/mL. In uremic patients, the free carbamazepine level may be a more useful guide for dosage
adjustments than the total level. In patients with severe uremia, subtherapeutic total carbamazepine levels
in the range of 1.0 to 2.0 mcg/mL may be associated with therapeutic free levels. Toxicity may occur in
these patients when the free carbamazepine level is > or =4.0 mcg/mL (even though the total
carbamazepine concentration is <15.0 mcg/mL). As with the serum levels of other anticonvulsant drugs,
total and free carbamazepine levels should be correlated with the patient's clinical condition. They are best
used as a guide in dose adjustment.
Reference Values:
CARBAMAZEPINE, TOTAL
Therapeutic: 4.0-12.0 mcg/mL
Critical value: > or =15.0 mcg/mL
CARBAMAZEPINE, FREE
Therapeutic: 1.0-3.0 mcg/mL
Critical value: > or =4.0 mcg/mL
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 396
Clin Phamacol 1997;44:21-27 3. Dasgupta A, Volk A: Displacement of valproic acid and carbamazepine
from protein binding in normal and uremic sera by tolmetin, ibuprofen, and naproxen: presence of
inhibitor in uremic serum that blocks valproic acid-naproxen interactions. Ther Drug Monit
1996;18:284-287 4. Moyer TP: Therapeutic drug monitoring. In Tietz Textbook of Clinical Chemistry.
Edited by CA Burtis, ER Ashwood. Fourth edition. Philadelphia, PA. WB Saunders Company 2005 pp
1237-1285 5. Patsalos PN, Berry DJ, Bourgeois BF, et al: Antiepileptic drugs-best practice guidelines for
therapeutic drug monitoring: A position paper by the subcommission on therapeutic drug monitoring,
ILAE Commission on Therapeutic Strategies. Epilepsia 2008;49(7):1239-1276
Reference Values:
Therapeutic concentration: 1.0-3.0 mcg/mL
Critical value: > or =4.0 mcg/mL
Reference Values:
Therapeutic: 4.0-12.0 mcg/mL Critical value: > or =15.0 mcg/mL
Clinical References: 1. Cereghino JJ, Meter JC, Brock JT, et al: Preliminary observations of serum
carbamazepine concentration in epileptic patients. Neurology 1973;23:357-366 2. Patsalos PN, Berry DJ,
Bourgeois BF, et al: Antiepileptic drugs-best practice guidelines for therapeutic drug monitoring: A
position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic
Strategies. Epilepsia 2008;49(7):1239-1276
Useful For: Monitoring patients exhibiting symptoms of carbamazepine toxicity whose serum
carbamazepine concentration is within the therapeutic range, but who may be producing significant levels
of the active metabolite epoxide
Reference Values:
CARBAMAZEPINE, TOTAL Therapeutic: 4.0-12.0 mcg/mL Critical value: > or =15.0 mcg/mL
Clinical References: 1. Theodore WH, Narang PK, Holmes MD, et al: Carbamazepine and its
epoxide: relation of plasma levels to toxicity and seizure control. Ann Neurol 1989;25:194-196 2. Tomson
T, Almkvist O, Nilsson BY, et al: Carbamazepine-10, 11-epoxide in epilepsy. A pilot study. Arch Neurol
1990;47:888-892 3. McKauge L, Tyrer JH, Eadie MI: Factors influencing simultaneous concentrations of
carbamazepine and its epoxide in plasma. Ther Drug Monit 1981;3:63-70 4. Brodie MJ, Forrest G,
Rapeport WG: Carbamazepine-10,11-epoxide concentrations in epileptics of carbamazepine alone and in
combination with other anticonvulsants. Br J Clin Pharmacol 1983;16:747-749 5. Shoeman JF, Elyas AA,
Brett EM, Lascelles PT: Correlation between plasma carbamazepine-10,11-epoxide concentration and
drug side-effects in children with epilepsy. Dev Med Child Neurol 1984;26:756-764
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 398
CARNP Carbapenemase Detection-Carba NP Test
62606 Clinical Information: Gram-negative bacilli (GNB) with acquired carbapenemases have
disseminated worldwide, rendering them a global threat. The therapeutic armamentarium for infections
caused by carbapenem-resistant Enterobacteriaceae (CRE) is limited, and CRE infections have been
associated with significant mortality. Enterobacteriaceae harboring Klebsiella pneumoniae
carbapenemase are endemic in some regions of the United States, and although still sporadic, GNB
harboring New Delhi metallo-beta-lactamase have been reported from several states. Timely detection
of these carbapenemases (along with emerging carbapenemases such as OXA-48 and VIM) is
important. Detection is challenging since isolates may have only borderline reductions in susceptibility
to carbapenems, and carbapenem resistance may be mediated by mechanisms other than
carbapenemases (eg, AmpC or extended-spectrum beta-lactamase with decreased membrane
permeability). While molecular methods are confirmatory, testing may not be immediately available and
may be limited by the number of targets assayed. The modified Hodge test suffers from lack of
specificity, a long turnaround time, and poor sensitivity for metallo-beta-lactamase detection. The Carba
NP test is preferred over the modified Hodge test due to improved specificity and faster turnaround
time. The Carba NP test is more specific than and as sensitive as the carbapenemase-modified Hodge
test. If an isolate is suspected to possess KPC or NDM carbapenemase (eg, due to local epidemiology),
KPC and NDM PCR (KPNRP / KPC (blaKPC) and NDM (blaNDM) in Gram-Negative Bacilli,
Molecular Detection, PCR) may be preferred over the Carba NP test.
Reference Values:
Negative
Clinical References: 1. Vasoo S, Cunningham SA, Kohner P, et al: Comparison of a novel, rapid
chromogenic biochemical assay, the Carba NP test, with the modified Hodge test for detection of
carbapenemase-producing Gram-negative bacilli. J Clin Microbiol 2013;51(9):3097-3101 2. Nordmann
P, Poirel L, Dortet L: Rapid detection of carbapenemase-producing Enterobacteriaceae. Emerg Infect
Dis 2012;18:1503-1507
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Useful For: As an adjunct in the assessment of pancreatic cysts, when used in conjunction with
carcinoembryonic antigen, amylase, imaging studies and cytology
Interpretation: Cyst fluid carbohydrate antigen 19-9 (CA19-9) concentrations < or =37 U/mL indicate
a low risk for a mucinous cyst, and are more consistent with serous cystadenoma or pseudocyst. The
sensitivity and specificity are approximately 19% and 98%, respectively, at this concentration. Correlation
of these test results with cytology and imaging is recommended.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Snozek CL, Jenkins SM, Bryant SC, et al: Analysis of CEA, CA19-9 and
amylase in pancreatic cyst fluid for diagnosis of pancreatic lesions. Clin Chem 2008;54(6 Suppl
S):A126-127 2. van der Waaij LA, van Dullemen HM, Porte RJ: Cyst fluid analysis in the differential
diagnosis of pancreatic cystic lesions: a polled analysis. Gastrointest Endosc 2005;62:383-389 3. Khalid
A, Brugge W: ACG practice guidelines for the diagnosis and management of neoplastic pancreatic cysts.
Am J Gastroenterol. 2007 Oct;102(10):2339-2349
Useful For: An adjunct to cytology to differentiate between malignancy-related ascites and benign
causes of ascites formation
Interpretation: A peritoneal fluid carbohydrate antigen 19-9 (CA 19-9) concentration >32 U/mL is
suspicious, but not diagnostic, of a malignancy-related ascites. This clinical decision limit cutoff yielded
44% sensitivity and 93% specificity in a study of 137 patients presenting with ascites. However, ascites
caused by malignancies not associated with increase serum CA 19-9 concentrations, including lymphoma,
mesothelioma, leukemia, and melanoma, routinely had CA 19-9 concentrations <32 U/mL. Therefore,
negative results should be interpreted with caution, especially in patients who have or are suspected of
having a malignancy not associated with elevated CA 19-9 levels in serum.
Reference Values:
An interpretive report will be provided.
Useful For: An adjuvant to cytology and imaging studies to differentiate between nonmalignant and
malignant causes of pleural effusions
Interpretation: A pleural fluid carbohydrate antigen 19-9 (CA 19-9) concentration of > or =20.0
U/mL is suspicious, but not diagnostic, of a malignant source of the effusion. This cutoff yielded a
sensitivity of 35%, specificity of 95%, and positive predictive value of 88% in a study of 200 patients
presenting with effusion. CA 19-9 concentrations were significantly higher in effusions caused by CA
19-9-secreting malignancies, including cholangiocarcinoma, colorectal, stomach, bile duct, lung,
ovarian, and pancreatic cancers. However, effusions caused by non-CA 19-9-secreting malignancies,
including lymphoma, mesothelioma, leukemia, and melanoma, routinely had CA 19-9 concentrations
<20.0 U/mL. Therefore, negative results should be interpreted with caution, especially in patients who
have or are suspected of having a non-CA 19-9-secreting malignancy. Correlation of all tumor marker
results with cytology and imaging is highly recommended.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Shitrit D, Zingerman B, Shitrit AB, et al: Diagnostic value of CYFRA
21-1, CEA, CA 19-9, CA 15-3, and CA 125 assays in pleural effusions: analysis of 116 cases and
review of the literature. Oncologist 2005;10:501-507 2. Hackbarth JS, Murata K, Reilly W,
Algeciras-Schimnich A: Performance of CEA and CA19-9 in identifying pleural effusions caused by
specific malignancies. Clin Biochem 2010 Sep;43(13-14):1051-1055
Useful For: Potentially useful adjunct for diagnosis and monitoring of pancreatic cancer May be used
for differentiating patients with cholangiocarcinoma and primary sclerosing cholangitis (PSC) from
those with PSC alone
Interpretation: Serial monitoring of carbohydrate antigen 19-9 (CA 19-9) should begin prior to
therapy to verify post-therapy decreases in CA 19-9 and to establish a baseline for evaluating possible
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recurrence. Single values of CA 19-9 are less informative. Elevated values may be caused by a variety
of malignant and nonmalignant conditions including cholangiocarcinoma, pancreatic cancer, and/or
colon cancer.
Reference Values:
<55 U/mL
Serum markers are not specific for malignancy, and values may vary by method.
Clinical References: Torok N, Gores GJ: Cholangiocarcinoma. Semin Gastrointest Dis 2001
Apr;12(2):125-132
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in this case most likely the defects do not involve the Golgi system, thus the molecular defect is different.
-CDG mixed type profile (type I and II together). In this type of profile one can have abnormal
tri-sialo/di-oligosaccharide transferrin ratio with the mono-oligosaccharide/di-oligosaccharide transferrin
ratio and/or the a-oligosaccharide/di-oligosaccharide transferrin ratio abnormal, and may have the
apolipoprotein CIII-1/apolipoprotein CIII-2 ratio and the apolipoprotein CIII-0/apolipoprotein CIII-2 ratio
normal or abnormal, depending if the defects involve Golgi apparatus. When the profile cannot be
categorized following the above classification, all the abnormal transferrin and/or Apo-CIII species will
be reported descriptively according to the molecular mass stating the possible structures. Reports of
abnormal results will include recommendations for additional biochemical and molecular genetic studies
to more precisely identify the correct form of CDG. Treatment options, the name and telephone number of
contacts who may provide studies at Mayo Clinic or elsewhere, and a telephone number for one of the
laboratory directors (if the referring physician has additional questions) will be provided.
Reference Values:
Ratio Normal Indeterminate Abnormal
Clinical References: 1. Freeze HH: Congenital disorders of glycosylation: CDG-I, CDG II, and
beyond. Curr Mol Med 2007;7:389-396 2. Freeze HH, Eklund EA, Ng BG, Patterson MC: Neurology of
inherited glycosylation disorders. Lancet Neurol 2012;11:453-466 3. Hennet T, Cabalzar J: Congenital
disorders of glycosylation: a concise chart of glycocalyx dysfunction. Trends Biochem Sci 2015
Jul;40(7):377-384 4. Freeze HH, Chong JX, Bamshad MJ, Ng BG: Solving glycosylation disorders:
fundamental approaches reveal complicated pathways. Am J Hum Genet 2014 Feb 6;94(2):161-175
Reference Values:
< or =0.10
0.11-0.12 (indeterminate)
Useful For: Screening for disorders with increased excretion of fructose, glucose, galactose,
disaccharides, oligosaccharides, and succinylpurines
Interpretation: The saccharide(s) present is named, identification of the probable source, and an
interpretive comment is provided.
Reference Values:
Negative
If positive, carbohydrate is identified.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 404
Interpretation: The toxic effects of carbon monoxide can be seen above 20% carboxyhemoglobin. It
must be emphasized that the carboxyhemoglobin concentration, although helpful in diagnosis, does not
always correlate with the clinical findings or prognosis. Factors other than carboxyhemoglobin
concentration that contribute to toxicity include length of exposure, metabolic activity, and underlying
disease, especially cardiac or cerebrovascular disease. Moreover, low carboxyhemoglobin
concentrations relative to the severity of poisoning may be observed if the patient was removed from the
carbon monoxide-contaminated environment a significant amount of time before blood sampling.
Reference Values:
Normal Concentration
Non-Smokers: 0-2%
Smokers: < or =9%
Toxic concentration: > or =20%
Clinical References: 1. Langman LJ, Bechtel L, Holstege CP: Clinical toxicology. In Tietz
Textbook of Clinical Chemistry and Molecular Diagnostics. Edited by CA Burtis, ER Ashwood, DE
Bruns. 5th edition. Elsevier Saunders, St. Louis, MO. 2012 pp 1109-1188 2. Disposition of Toxic Drugs
and Chemicals in Man. 10th edition. Edited by RC Baselt. South Beach CA, Biomedical Publications,
2014 3. Instruction Manual: ABL80 FLEX CO-OX analyzer-OSM version, Radiometer Medical ApS,
Denmark, 2016
Reference Values:
Negative
Positives are reported with a quantitative GC-MS result.
Cutoff concentrations:
IMMUNOASSAY SCREEN
<50 ng/mL
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THC CARBOXYLIC ACID BY GC-MS
<3 ng/mL
Clinical References: Moyer TP, Palmen MA, Johnson P, et al: Marijuana testing-how good is it?
Mayo Clin Proc 1987;62:413-417
Reference Values:
Negative
Cutoff concentration:
Carboxy-THC- by GC/MS <3.0 ng/mL
Clinical References: Moyer TP, Palmen MA, Johnson P, et al: Marijuana testing-how good is it?
Mayo Clin Proc 1987;62:413-417
Useful For: When used in conjunction with imaging studies, cytology, and other pancreatic cyst fluid
tumor markers: -Distinguishing between mucinous and nonmucinous pancreatic cysts -Determining the
likely type of malignant pancreatic cyst
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 406
Interpretation: A pancreatic cyst fluid carcinoembryonic antigen (CEA) concentration of > or =200
ng/mL is very suggestive for a mucinous cyst but is not diagnostic. The sensitivity and specificity for
mucinous lesions are approximately 62% and 93%, respectively, at this concentration. Cyst fluid CEA
concentrations of < or =5 ng/mL indicate a low risk for a mucinous cyst, and are more consistent with
serous cystadenoma, fluid collections complicating pancreatitis, cystic neuroendocrine tumor, or
metastatic lesions. CEA values between these extremes have limited diagnostic value.
Reference Values:
An interpretive report will be provided.
Useful For: An adjunct to cytology to differentiate between malignancy-related and benign causes of
ascites formation
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Torresini RJ, Prolla JC, Diehl AR, et al: Combined carcinoembryonic
antigen and cytopathologic examination in ascites. Acta Cytol 2000;44(5):778-782 2. Tuzun Y, Yilmaz
S, Dursun M, et al: How to increase the diagnostic value of malignancy-related ascites: discriminative
ability of the ascitic tumour markers. J Int Med Res 2009;37(1):87-95
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 407
(including congestive heart failure, pneumonia, pulmonary embolism, and liver cirrhosis) or malignant
conditions (including lung, breast, and lymphoma cancers). Diagnosing the cause of an effusion can be
difficult, often requiring cytological examination of the pleural fluid and imaging studies of the pleural
tissue. Analysis of various tumor markers in pleural fluid has shown that these markers can differentiate
between effusions caused by nonmalignant and malignant conditions and can enhance cytology and
imaging findings. Carcinoembryonic antigen (CEA) is a glycoprotein produced during fetal
development. Nonsmoking, healthy adults typically produce low to undetectable levels of CEA. Serum
concentrations of CEA may be elevated in patients with certain malignancies that secrete CEA into
circulation, including medullary thyroid carcinoma and breast, gastrointestinal tract, colorectal, liver,
lung, ovarian, pancreatic, and prostate cancers. Pleural fluid concentrations of CEA have been reported
to be elevated in patients with certain malignancies. Malignancies that can secrete CEA and elevate
serum CEA concentrations, including lung, breast, ovarian, gastrointestinal, and colorectal cancers,
typically also elevate CEA in pleural fluid. In contrast, malignancies that do not secrete CEA, including
mesothelioma, lymphoma, leukemia, and melanoma, have low concentrations of CEA in pleural fluid
comparable to concentrations observed in non-malignant effusions. Elevated CEA concentrations in
pleural fluid have also been reported with certain nonmalignant conditions, including liver cirrhosis,
pancreatitis, complicated parapneumonic effusions and empyemas, and rarely with tuberculosis. CEA
results should be used in conjunction with cytological analysis of pleural fluid, imaging studies, and
other clinical findings.
Useful For: An adjuvant to cytology and imaging studies to differentiate between nonmalignant and
malignant causes of pleural effusions
Interpretation: A pleural fluid carcinoembryonic antigen (CEA) concentration of > or =3.5 ng/mL is
suspicious but not diagnostic of a malignant source of the effusion. This cutoff yielded a sensitivity of
52%, specificity of 95%, and part per volume of 93% in a study of 200 patients presenting with effusion.
CEA concentrations were significantly higher in effusions caused by CEA-secreting malignancies,
including lung, breast, ovarian, gastrointestinal, and colorectal cancers. However, effusions caused by
non-CEA-secreting malignancies, including lymphoma, mesothelioma, leukemia, and melanoma,
routinely had CEA concentrations <3.5 ng/mL. Therefore, negative results should be interpreted with
caution, especially in patients who have or are suspected of having a non-CEA-secreting malignancy.
Correlation of all tumor marker results with cytology and imaging is highly recommended.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Shitrit D, Zingerman B, Shitrit AB, et al: Diagnostic value of CYFRA 21-1,
CEA, CA 19-9, CA 15-3, and CA 125 assays in pleural effusions: analysis of 116 cases and review of the
literature. Oncologist 2005;10:501-507 2. Hackbarth JS, Murata K, Reilly W, Algeciras-Schimnich A:
Performance of CEA and CA19-9 in identifying pleural effusions caused by specific malignancies. Clin
Biochem 2010 Sep;43(13-14):1051-1055 3. Garcia-Pachon E, Padilla-Navas I, Dosda MD,
Miralles-Llopis A: Elevated level of carcinoembryonic antigen in nonmalignant pleural effusions. Chest
1997;111:643-647
Useful For: Monitoring colorectal cancer and selected other cancers such as medullary thyroid
carcinoma May be useful in assessing the effectiveness of chemotherapy or radiation treatment
Carcinoembryonic antigen levels are not useful in screening the general population for undetected
cancers.
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Interpretation: Grossly elevated carcinoembryonic antigen (CEA) concentrations (>20 ng/mL) in a
patient with compatible symptoms are strongly suggestive of the presence of cancer and also suggest
metastasis. Most healthy subjects (97%) have values < or =3.0 ng/mL. After removal of a colorectal
tumor, the serum CEA concentration should return to normal by 6 weeks, unless there is residual tumor.
Increases in test values over time in a patient with a history of cancer suggest tumor recurrence.
Reference Values:
Nonsmokers: < or =3.0 ng/mL
Some smokers may have elevated CEA, usually <5.0 ng/mL.
Serum markers are not specific for malignancy, and values may vary by method.
Clinical References: 1. Chan DW, Booth RA, Diamandis EP, et al: In Tietz Textbook of Clinical
Chemistry and Molecular Diagnostics. Fourth edition. Edited by CA Burtis, ER Ashwood, DE Bruns.
St. Louis, Elsevier, Inc., 2006 pp 768-769 2. Locker, GY, Hamilton S, Harris J, et al: ASCO 2006
update of recommendations for the use of tumor markers in gastrointestinal cancer. J Clin Oncol
2006;24:5313-5327 3. Moertel CG, Fleming TR, Macdonald JS, et al: An evaluation of the
carcinoembryonic antigen (CEA) test for monitoring patients with resected colon cancer. JAMA
1993;270:943-947
Interpretation: Increased values are seen in approximately 60% of patients with meningeal
carcinomatosis.
Reference Values:
<0.6 ng/mL
Tumor markers are not specific for malignancy, and values may vary by method.
Clinical References: 1. Klee GG, Tallman RD, Goellner JR, Yanagihara T: Elevation of
carcinoembryonic antigen in cerebrospinal fluid among patients with meningeal carcinomatosis. Mayo
Clin Proc 1986;61:9-13 2. Go VLW, Zamcheck N: The role of tumor markers in the management of
colorectal cancer. (Cancer 50[Suppl 1]);1982:2618-2623 3. Moertel CG, et al: An evaluation of the
carcinoembryonic antigen (CEA) test for monitoring patients with resected colon cancer. JAMA
1993;270:943-947
Clinical References: 1. Costa MJ, Kenny MB, Judd R: Adenocarcinoma and adenosquamous
carcinoma of the uterine cervix. Histologic and immunohistochemical features with clinical correlation.
Int J Surg Pathol 1994;1:181-189 2. Sheahan K, OBrien MJ, Burke B, et al: Differential reactivities
of carcinoembryonic antigen (CEA) and CEA-related monoclonal and polyclonal antibodies in common
epithelial malignancies. Am J Clin Pathol 1990;94:157-164 3. Sumitoma S, Kumasa S, Mitani H, et al:
Comparison of CEA distribution in lesions and tumors of salivary glands as determined with monoclonal
and polyclonal antibodies. Circhows Arch B 1987;53:133-139 4. Wong HH, Chu P:
Immunohistochemical features of the gastrointestinal tract tumors. J Gastrointest Oncol
2012;3(3):262-284
Clinical References: 1. Costa MJ, Kenny MB, Judd R: Adenocarcinoma and adenosquamous
carcinoma of the uterine cervix. Histologic and immunohistochemical features with clinical correlation.
Int J Surg Pathol 1994;1:181-189 2. Sheahan K, OBrien MJ, Burke B, et al: Differential reactivities
of carcinoembryonic antigen (CEA) and CEA-related monoclonal and polyclonal antibodies in common
epithelial malignancies. Am J Clin Pathol 1990;94:157-164 3. Sumitoma S, Kumasa S, Mitani H, et al:
Comparison of CEA distribution in lesions and tumors of salivary glands as determined with monoclonal
and polyclonal antibodies. Circhows Arch B 1987;53:133-139 4. Wong HH, Chu P:
Immunohistochemical features of the gastrointestinal tract tumors. J Gastrointest Oncol
2012;3(3):262-284
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
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Interpretation: Detection of IgE antibodies in serum (Class 1 or greater) indicates an increased
likelihood of allergic disease as opposed to other etiologies and defines the allergens that may be
responsible for eliciting signs and symptoms. The level of IgE antibodies in serum varies directly with
the concentration of IgE antibodies expressed as a class score or kU/L.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Evaluating risk of atherosclerosis and adverse events related to atherosclerotic disease
Interpretation: Elevated plasma fibrinogen confers increased risk of atherosclerosis, acute
myocardial infarction, and stroke.
Reference Values:
<340 mg/dL 1st quartile (low risk)
340-390 mg/dL 2nd quartile
391-450 mg/dL 3rd quartile
>450 mg/dL 4th quartile (high risk)
Clinical References: 1. Stec JJ, Silbershatz H, Tofler GH, et al: Association of fibrinogen with
cardiovascular risk factors and cardiovascular disease in the Framingham offspring population.
Circulation 2000;102:1634-1638 2. Antonini-Canterin F, Carrubba S, Gullace G, et al: Association
between carotid atherosclerosis and metabolic syndrome: Results from the ISMIR study. Angiology
2010;61:443-448 3. Kaptoge S, Di Angelantonio E, Pennells L, et al: C-reactive protein, fibrinogen, and
cardiovascular disease prediction. N Engl J Med 2012;367:1310-1320 4. Blankengerg S, Luc G,
Ducimetiere P, et al: The Prospective Epidemiological Study of Myocardial Infarction (PRIME).
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 411
Circulation 2003;108:2453-2459 5. Jarvie J, Whooley M, Regan M, et al: Effect of physical activity on
biomarkers of inflammation and insulin resistance over years in outpatients with coronary heart disease.
Am J Cardiol 2014;114:1192-1197
Useful For: Evaluation of congenital heart disease Evaluation of pulmonary hypertension Evaluation
of complex ischemic or valvular heart disease Evaluation of cardiomyopathies Evaluation of sudden
unexplained death Not for cases under litigation
Reference Values:
Abnormalities will be compared to reported reference values.
Clinical References: 1. Edwards WD: Congenital heart disease. In Anderson's Pathology. Edited by
J Linder, I Damjanov. St. Louis, MO, Mosby-Year Book, Inc., 1996, pp 1339-1396 2. Edwards WD:
Pathology of myocardial infarction and reperfusion. In Acute Myocardial Infarction. Edited by BJ Gersh,
S Rahimtoola. New York, Chapman and Hall, 1997, pp 16-50 3. Edwards WD: Cardiomyopathies. Major
Prob Path 1991;23:257-309
Useful For: Assessment for risk of developing cardiovascular disease, major adverse cardiovascular
events, or ischemic cerebrovascular events
Interpretation: Specific interpretations are provided based on lipid results according to Mayo Clinic
care process models. Mayo Clinic has adopted the National Lipid Association classifications, which are
included as reference values on Mayo Clinic and Mayo Medical Laboratories reports (see Reference
Values). More aggressive treatment strategies may be pursued in patients determined to be at increased
risk.
Reference Values:
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Age 2-17 years >18 years
Non-HDL Cholesterol (mg/dL) ** Acceptable: high: 120-144 High: > * Desirable: Above Desirable: 130-159
or =145 mg/dL Borderline high: 160-189
mg/dL High: 190-219 mg/dL Very
high: > or =220 mg/dL
LDL Cholesterol (mg/dL) ** Acceptable: high: 110-129 High: > *** Desirable: Desirable: 100-129
or =130 Borderline high: 130-159 High:
160-189 Very high: > or =190
HDL Cholesterol (mg/dL) ** Low: low: 40-45 Acceptable: > 45 *** Males: > or =40 Females: > or =50
Total Cholesterol (mg/dL) ** Acceptable: high: 170-199 High: > * Desirable: < 200 Borderline high:
or =200 200 - 239 High: > or = 240
LIPOPROTEIN (a) (mg/dL) < or =30 mg/dL Values >30 mg/dL < or =30 mg/dL Values >30 mg/dL
may suggest increased risk of may suggest increased risk of
coronary heart disease. coronary heart disease.
C-REACTIVE PROTEIN HIGH * Lower risk: Higher risk: >=2.0 mg/L * Lower risk: Higher risk: >=2.0 mg/L
SENSITIVITY Acute inflammation: >10.0 mg/L Acute inflammation: >10.0 mg/L
Triglycerides (mg/dL) ** Acceptable: high: 75-99 ** Acceptable: high: 90-129 * Normal: high: 150-199 High:
High: > or =100 High: > or =130 200-499 Very high: > or =500
*National Lipid Association
2014 **Expert Panel on
Integrated Guidelines for
Cardiovascular Health and
Risk Reduction in Children and
Adolescents ***National
Cholesterol Education Program
(NCEP)
Clinical References: 1. Jacobson TA, Ito MK, Maki KC, et al: National Lipid Association
recommendations for patient-centered management of dyslipidemia: part 1 - executive summary. J Clin
Lipidol 2014 Sep-Oct;8(5):473-488 2. Perk J, DeBacker G, Gohlke H, et al: European Guidelines on
cardiovascular disease prevention in clinical practice. Eur Heart J 2012;33:1635-1701 3. Goff DC,
Lloyd-Jones DM, Gennett G, et al: 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk.
Circulation 2014;129:S49-S73 4. Expert Panel on Integrated Guidelines for Cardiovascular Health and
Risk Reduction in Children and Adolescents; National Heart, Lung, and Blood Institute: Expert panel on
integrated guidelines for cardiovascular health and risk reduction in children and adolescents. Pediatrics
2011;128;S213-S256 5. Ridker PM, Rifai N, Rose L, et al: Comparison of C-reactive protein and
low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med
2002 Nov 14;347(20):1557-1565 6. Ridker PM, Danielson E, Fonseca FA, et al: Reduction in C-reactive
protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective
study of the JUPITER trial. Lancet 2009;373:11751182
Reference Values:
<0.35 kU/L
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CPT2Z Carnitine Palmitoyltransferase II Deficiency, Full Gene Analysis
35398 Clinical Information: Carnitine palmitoyltransferase II (CPT II) deficiency is an autosomal recessive
disorder of long-chain fatty-acid oxidation. There are 3 distinct clinical phenotypes: a lethal neonatal
form, an early-onset infantile form, and a late-onset adult myopathic form. The lethal neonatal and
early-onset infantile forms are characterized by liver failure, cardiomyopathy, seizures, hypoketotic
hypoglycemia, peripheral myopathy and early death. The adult-onset myopathic form is the most common
type and is characterized by exercise-induced muscle pain and weakness and may be associated with
myoglobinuria. Males are more likely to be affected with the myopathic form than females. Initial
screening can be done with plasma acylcarnitines. Definitive diagnosis can be made by detection of
reduced CPT enzyme activity. Mutations in the CPT2 gene are responsible for CPT II deficiency and
sequencing of this gene is recommended after positive biochemical analysis.
Interpretation: All detected alterations are evaluated according to American College of Medical
Genetics recommendations.(1) Variants are classified based on known, predicted, or possible
pathogenicity and reported with interpretive comments detailing their potential or known significance.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for
standards of interpretation and reporting of sequence variations: revisions 2007. Genet Med
2008;10(4):294-300 2. Bonnefont JP, Djouadi F, Prip-Buus C, et al: Carnitine palmitoyltransferases 1 and
2: biochemical, molecular and medical aspects. Mol Aspects Med 2004 Oct-Dec;25(5-6):495-520 3.
Siguake E, Rakheja D, Kitson K, Bennet M: Carnitine palmitoyltransferase II deficiency: a clinical,
biochemical, and molecular review. Lab Invest 2003 Nov;83(11):1543-1554
Useful For: Evaluation of patients with a clinical suspicion of a wide range of conditions including
organic acidemias, fatty acid oxidation disorders, and primary carnitine deficiency
Interpretation: When abnormal results are detected, a detailed interpretation is given, including an
overview of the results and of their significance, a correlation to available clinical information, elements
of differential diagnosis, recommendations for additional biochemical testing, and a phone number to
reach one of the laboratory directors in case the referring physician has additional questions.
Reference Values:
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Total Carnitine (TC)Free Carnitine (FC) Acylcarnitine (AC) AC/FC Ratio
Clinical References: 1. Magoulas PL, El-Hattab AW: Systemic primary carnitine deficiency: an
overview of clinical manifestations, diagnosis, and management. Orphanet Journal of Rare Diseases
2012,7:68 Available from URL: http://www.ojrd.com/content/7/1/68. Accessed 1/22/15 2. Longo N,
Amat di San Filippo C, Pasquali M: Disorders of carnitine transport and the carnitine cycle. Am J Med
Genet C Semin Med Genet 2006;142C(2):77-85 3. Zammit VA, Ramsay RR, Bonomini M, Arduini A:
Carnitine, mitochondrial function and therapy. Adv Drug Deliv Rev 2009;61(14):1353-1362
Useful For: Evaluation of patients with a clinical suspicion of a wide range of conditions including
organic acidemias, fatty acid oxidation disorders, and primary carnitine deficiency
Interpretation: When abnormal results are detected, a detailed interpretation is given, including an
overview of the results and of their significance, a correlation to available clinical information, elements
of differential diagnosis, recommendations for additional biochemical testing, and a phone number to
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 415
reach one of the laboratory directors in case the referring physician has additional questions.
Reference Values:
Total Carnitine (TC)Free Carnitine (FC) Acylcarnitine (AC) AC/FC Ratio
Clinical References: 1. Magoulas PL, El-Hattab AW: Systemic primary carnitine deficiency: an
overview of clinical manifestations, diagnosis, and management. Orphanet Journal of Rare Diseases
2012,7:68 Available from URL: http://www.ojrd.com/content/7/1/68. Accessed 1/22/15 2. Longo N,
Amat di San Filippo C, Pasquali M: Disorders of carnitine transport and the carnitine cycle. Am J Med
Genet C Semin Med Genet 2006;142C(2):77-85 3. Zammit VA, Ramsay RR, Bonomini M, Arduini A:
Carnitine, mitochondrial function and therapy. Adv Drug Deliv Rev 2009;61(14):1353-1362
Useful For: Evaluation of patients with a clinical suspicion of a wide range of conditions including
organic acidemias and fatty acid oxidation disorders Monitoring carnitine treatment
Interpretation: When abnormal results are detected, a detailed interpretation is given, including an
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 416
overview of the results and of their significance, a correlation to available clinical information, elements
of differential diagnosis, recommendations for additional biochemical testing and a phone number to
reach one of the laboratory directors in case the referring physician has additional questions.
Reference Values:
FREE
77-214 nmol/mg of creatinine
TOTAL
180-412 nmol/mg of creatinine
RATIO
Acyl to free: 0.7-3.4
Clinical References: 1. Chalmers RA, Roe CR, Stacey TE, et al: Urinary excretion of l-carnitine
and acylcarnitines by patients with disorders of organic acid metabolism: evidence for secondary
insufficiency of l-carnitine. Ped Res 1984;18:1325-1328 2. Magoulas PL, El-Hattab AW: Systemic
primary carnitine deficiency: an overview of clinical manifestations, diagnosis, and management.
Orphanet Journal of Rare Diseases 2012,7:68 Available from URL:
http://www.ojrd.com/content/7/1/68. Accessed 1/22/15 3. Longo N, Amat di San Filippo C, Pasquali M:
Disorders of carnitine transport and the carnitine cycle. Am J Med Genet C Semin Med Genet
2006;142C(2):77-85 4. Zammit VA, Ramsay RR, Bonomini M, Arduini A: Carnitine, mitochondrial
function and therapy. Adv Drug Deliv Rev 2009;61(14):1353-1362
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Wang GL, Wang J, Douglas G, et al: Expanded molecular features of
carnitine acyl-carnitine translocase (CACT) deficiency by comprehensive molecular analysis. Mol
Genet Metab 2011 Aug;103(4):349-357 2. Rubio-Gozalbo ME, Bakker, JA, Waterham, HR, Wanders
RJA: Carnitine-acylcarnitine translocase deficiency, clinical, biochemical and genetic aspects. Mol
Aspects Med 2004 Oct-Dec;25(5-6):521-532
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Interpretation: High levels are useful to rule out steatorrhea but lower values lack specificity. There is
poor sensitivity. High in the serum of those ingesting large amounts of vegetables.
Reference Values:
3 - 91 ug/dL
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical utility
of food-specific IgG tests has not been established. These tests can be used in special clinical situations to
select foods for evaluation by diet elimination and challenge in patients who have food-related
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complaints. It should be recognized that the presence of food-specific IgG alone cannot be taken as
evidence of food allergy and only indicates immunologic sensitization by the food allergen in question.
This test should only be ordered by physicians who recognize the limitations of the test.
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Reference Values:
< 2 mcg/mL
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The reference range listed on the report is the lower limit of quantitation for the assay. The clinical
utility of food-specific IgG tests has not been established. These tests can be used in special clinical
situations to select foods for evaluation by diet elimination and challenge in patients who have
food-related complaints. It should be recognized that the presence of food-specific IgG alone cannot be
taken as evidence of food allergy and only indicates immunologic sensitization by the food allergen in
question. This test should only be ordered by physicians who recognize the limitations of the test.
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 420
< 2 mcg/mL
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical utility
of food-specific IgG tests has not been established. These tests can be used in special clinical situations to
select foods for evaluation by diet elimination and challenge in patients who have food-related
complaints. It should be recognized that the presence of food-specific IgG alone cannot be taken as
evidence of food allergy and only indicates immunologic sensitization by the food allergen in question.
This test should only be ordered by physicians who recognize the limitations of the test.
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Establishing a diagnosis of familial hypocalciuric hypercalcemia As part of the workup of
some patients with primary hyperparathyroidism Establishing a diagnosis of neonatal severe primary
hyperparathyroidism Establishing a diagnosis of autosomal dominant hypoparathyroidism As part of the
workup of idiopathic hypoparathyroidism As part of the workup of patients with Bartter syndrome
Interpretation: Evaluation and categorization of variants is performed using the most recent published
American College of Medical Genetics recommendations as a guideline.(1) Variants are classified based
on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their
potential or known significance. Multiple in silico evaluation tools may be used to assist in the
interpretation of these results. The accuracy of predictions made by in silico evaluation tools is highly
dependent upon the data available for a given gene, and predictions made by these tools may change over
time. Results from in silico evaluation tools should be interpreted with caution and professional clinical
judgment.
Reference Values:
An interpretive report will be provided
Clinical References: 1. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the
interpretation of sequence variants: a joint consensus recommendation of the American College of
Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med
2015;17:405-423 2. Hendy GN, D'Souza-Li L, Yang B, et al: Mutations of the calcium-sensing receptor
(CASR) in familial hypocalciuric hypercalcemia, neonatal severe hypocalciuric hyperparathyroidism, and
autosomal dominant hypocalcemia. Hum Mutat 2000 Oct;16(4):281-296. The authors maintain a CASR
polymorphism/mutation database available at www.casrdb.mcgill.ca/ 3. Lienhardt A, Bai M, Lgarde JP, et
al: Activating mutations of the calcium-sensing receptor: management of hypocalcemia. J Clin Endocrinol
Metab 2001 Nov;86(1):5313-5323 4. Hu J, Spiegel AM: Naturally occurring mutations of the
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 422
extracellular Ca2+ -sensing receptor: implications for its structure and function. Trends Endocrinol Metab
2003 Aug;14(6):282-288 5. Naesens M, Steels P, Verberckmoes R, et al: Bartter's and Gitelman's
syndromes: from gene to clinic. Nephron Physiol 2004;96(3):65-78 6. Egbuna OI, Brown EM:
Hypercalcaemic and hypocalcaemic conditions due to calcium-sensing receptor mutations. Best Pract Res
Clin Rheumatol 2008;22:129-148
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 423
immune response to allergen(s) that may be associated with allergic disease. The allergens chosen for
testing often depend upon the age of the patient, history of allergen exposure, season of the year, and
clinical manifestations. In individuals predisposed to develop allergic disease(s), the sequence of
sensitization and clinical manifestations proceed as follows: eczema and respiratory disease (rhinitis and
bronchospasm) in infants and children less than 5 years due to food sensitivity (milk, egg, soy, and
wheat proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
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polymorphism, COMT*2, reduces the maximum activity of the variant enzyme by 25% and also results in
significantly less immunoreactive COMT protein, resulting in a 3- to 4-fold decrease in activity compared
to wild type COMT*1. The COMT*2 polymorphism has been linked to prefrontal cortex cognitive
response to antipsychotic medications. Schizophrenia patients homozygous for the *2 polymorphism
displayed improved cognition following drug treatment. Patients homozygous for *1 did not have
improved cognition following treatment.(6) A second polymorphism has been identified in exon 4 that
results in a threonine substitution for alanine (Ala52/102Thr). This polymorphism, COMT*3, does not
reduce enzyme activity and is predicted to be a normally functioning allele.
Useful For: Early identification of patients who may show cognitive improvement with treatment for
schizophrenia; this is associated with the COMT*2/ COMT*2 genotype Investigation of inhibitor
dosing for decreasing L-dopa metabolism Research use for assessing estrogen metabolism Genotyping
patients who prefer not to have venipuncture done
Interpretation: An interpretive report will be provided. The normal genotype (wild type) for COMT
is *1/*1. COMT*2 (Val108/158Met) leads to a reduced activity allele. COMT*3 (Ala52/102Thr) is a
normal activity allele. The following information outlines the relationship between polymorphisms
detected in this assay and the effect on the activity of the enzyme produced by that allele: COMT Allele
Amino Acid Change Effect on Enzyme Activity/Metabolism *1 None (wild-type) Normal/Extensive *2
Val108/158Met Reduced/Poor *3 Ala52/102Thr Normal/Extensive
Reference Values:
An interpretive report will be provided.
Useful For: Early identification of patients who may show cognitive improvement with treatment for
schizophrenia, this is associated with the COMT*2/ COMT*2 genotype Investigation of inhibitor dosing
for decreasing L-DOPA metabolism Research use for assessing estrogen metabolism
Interpretation: An interpretive report will be provided. The normal genotype (wild type) for COMT is
*1/*1. COMT*2 (Val108/158Met) leads to a reduced activity allele. COMT*3 (Ala52/102Thr) is a
normal activity allele. The following information outlines the relationship between polymorphisms
detected in this assay and the effect on the activity of the enzyme produced by that allele: COMT Allele
Amino Acid Change Effect on Enzyme Activity/Metabolism *1 None (wild-type) Normal/Extensive *2
Val108/158Met Reduced/Poor *3 Ala52/102Thr Normal/Extensive
Reference Values:
An interpretive report will be provided.
Useful For: An auxiliary test to fractionated plasma and urine metanephrine measurements in the
diagnosis of pheochromocytoma and paraganglioma An auxiliary test to urine vanillylmandelic acid and
homovanillic acid determination in the diagnosis and follow-up of patients with neuroblastoma and
related tumors
Interpretation: Diagnosis of Pheochromocytoma: This test should not be used as the first-line test
for pheochromocytoma. PMET / Metanephrines, Fractionated, Free, Plasma (the most sensitive assay)
and/or METAF / Metanephrines, Fractionated, 24 Hour, Urine (almost as sensitive and highly specific)
are the recommended first-line laboratory tests for pheochromocytoma. However, urine catecholamine
measurements can still be useful in patients whose plasma metanephrines or urine metanephrines
measurements do not completely exclude the diagnosis. In such cases, urine catecholamine specimens
have an 86% diagnostic sensitivity when cut-offs of >80 mg/24 hour for norepinephrine and >20 mg/24
hour for epinephrine are employed. Unfortunately, the specificity of these cut-off levels for separating
tumor patients from other patients with similar symptoms is only 88%. When more specific (98%)
decision levels of >170 mg/24 hours for norepinephrine or >35 mg/24 hours for epinephrine are used,
the assays sensitivity falls to about 77%. Diagnosis of Neuroblastoma: Vanillylmandelic acid,
homovanillic acid, and sometimes urine catecholamine measurements on spot urine or 24-hour urine are
the mainstay of biochemical diagnosis and follow-up of neuroblastoma; 1 or more of these tests may be
elevated.
Reference Values:
NOREPINEPHRINE
<1 year: <11 mcg/24 hours
1 year: 1-17 mcg/24 hours
2-3 years: 4-29 mcg/24 hours
4-6 years: 8-45 mcg/24 hours
7-9 years: 13-65 mcg/24 hours
> or =10 years: 15-80 mcg/24 hours
EPINEPHRINE
<1 year: <2.6 mcg/24 hours
1 year: <3.6 mcg/24 hours
2-3 years: <6.1 mcg/24 hours
4-9 years: 0.2-10.0 mcg/24 hours
10-15 years: 0.5-20.0 mcg/24 hours
> or =16 years: <21 mcg/24 hours
DOPAMINE
<1 year: <86 mcg/24 hours
1 year: 10-140 mcg/24 hours
2-3 years: 40-260 mcg/24 hours
> or =4 years: 65-400 mcg/24 hours
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CATP Catecholamine Fractionation, Free, Plasma
8532 Clinical Information: The catecholamines (dopamine, epinephrine, and norepinephrine) are derived
from tyrosine via a series of enzymatic conversions. All 3 catecholamines are important neurotransmitters
in the central nervous system and also play a crucial role in the autonomic regulation of many homeostatic
functions, namely, vascular tone, intestinal and bronchial smooth muscle tone, cardiac rate and
contractility, and glucose metabolism. Their actions are mediated via alpha and beta adrenergic receptors
and dopamine receptors, all existing in several subforms. The 3 catecholamines overlap, but also differ in
their receptor activation profile and consequent biological actions. The systemically circulating fraction of
the catecholamines is derived almost exclusively from the adrenal medulla, with small contributions from
sympathetic ganglia. The catecholamines are normally present in the plasma in minute amounts, but levels
can increase dramatically and rapidly in response to change in posture, environmental temperature,
physical and emotional stress, hypovolemia, blood loss, hypotension, hypoglycemia, and exercise. In
patients with pheochromocytoma (a potentially curable tumor of catecholamine-producing cells of the
adrenal medulla), or less commonly of sympathetic ganglia (paraganglioma), plasma catecholamine levels
may be continuously or episodically elevated. This results in episodic or sustained hypertension and in
intermittent attacks of palpitations, cardiac arrhythmias, headache, sweating, pallor, anxiety, tremor, and
nausea. Intermittent or continuous elevations of the plasma levels of 1 or several of the catecholamines
may also be observed in patients with neuroblastoma and related tumors (ganglioneuroblastomas and
ganglioneuromas) and, very occasionally, in other neuroectodermal tumors. At the other end of the
spectrum, inherited and acquired syndromes of autonomic dysfunction or failure and autonomic
neuropathies are characterized by either inadequate production of 1 or several of the catecholamines or by
insufficient release of catecholamines upon appropriate physiological stimuli (eg, change in posture from
supine to standing, cold exposure, exercise, stress).
Interpretation: Diagnosis of Pheochromocytoma: This test should not be used as the first-line test for
pheochromocytoma, as plasma catecholamine levels may not be continuously elevated, but only secreted
during a "spell." By contrast, production of metanephrines (catecholamine metabolites) appears to be
increased continuously. The recommended first-line laboratory tests for pheochromocytoma are: -PMET /
Metanephrines, Fractionated, Free, Plasma: the most sensitive assay -METAF / Metanephrines,
Fractionated, 24 Hour, Urine: highly specific and almost as sensitive as PMET However, plasma
catecholamine measurements can still be useful in patients whose plasma metanephrine or urine
metanephrine measurements do not completely exclude the diagnosis. In such cases, plasma
catecholamine specimens, if drawn during a "spell," have a 90% to 95% diagnostic sensitivity when
cutoffs of >750 pg/mL for norepinephrine and >110 pg/mL for epinephrine are employed. A lower value
during a "spell," particularly when plasma or urinary metanephrine measurements were also normal,
essentially rules out pheochromocytoma. Unfortunately, the specificity of these high-sensitivity cutoff
levels is not good for separating tumor patients from other patients with similar symptoms. When more
specific (95%) decision levels of 2,000 pg/mL for norepinephrine or 200 pg/mL for epinephrine are used,
the assay's sensitivity falls to about 85%. Diagnosis of Neuroblastoma: Vanillylmandelic acid,
homovanillic acid, and sometimes urine catecholamine measurements on spot urine or 24-hour urine are
the mainstay of biochemical diagnosis and follow-up of neuroblastoma. Plasma catecholamine levels can
aid diagnosis in some cases, but diagnostic decision levels are not well established. The most useful
finding is disproportional elevations in 1 of the 3 catecholamines, particularly dopamine, which may be
observed in these tumors. Diagnosis of Autonomic Dysfunction or Failure and Autonomic Neuropathy:
Depending on the underlying cause and pathology, autonomic dysfunction or failure and autonomic
neuropathies are associated with subnormal resting norepinephrine levels, or an absent rise of
catecholamine levels in response to physiological release stimuli (eg, change in posture from supine to
standing, cold exposure, exercise, stress), or both. In addition, there may be significant abnormalities in
the ratios of the plasma values of the catecholamines to each other (normal:
norepinephrine>epinephrine>dopamine). This is observed most strikingly in the inherited dysautonomic
disorder dopamine-beta-hydroxylase deficiency, which results in markedly elevated plasma dopamine
levels and a virtually total absence of plasma epinephrine and norepinephrine.
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Reference Values:
NOREPINEPHRINE
Supine: 70-750 pg/mL
Standing: 200-1,700 pg/mL
EPINEPHRINE
Supine: < or =111 pg/mL
Standing: < or =141 pg/mL
DOPAMINE
<30 pg/mL (no postural change)
Reference Values:
<0.35 kU/L
Magnesium (mg/g)
Magnesium concentrations in stool water above the normal levels of 0.7-1.2 mg/mL have been
indicative of surreptitious abuse of magnesium containing laxatives.
NMS Labs Calculated Normal: approximately 0.5-10 mg/g (Based on the reported range of
magnesium eliminated per day in stool and the range of stool mass per day in adults).
Not for clinical diagnostic purposes.
Phosphorus (mg/g)
Phosphorus concentration in stool water averaged 1.8 +/- 0.3 mg/mL (ranged from 0.3-4.2 mg/mL)
following administration of 105 mmol of sodium phosphate.
NMS Labs calculated normal: approximately 1.4-22 mg/g (Based on the reported range of phosphorus
eliminated per day in stool and the range of stool mass per day in adults).
Not for clinical diagnostic purposes.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 429
FCAFG Cauliflower IgG
57680 Interpretation: mcg/mL of IgG Lower Limit of Quantitation 2.0 Upper Limit of Quantitation 200
Reference Values:
<2 mcg/mL
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical utility
of food-specific IgG tests has not been established. These tests can be used in special clinical situations to
select foods for evaluation by diet elimination and challenge in patients who have food-related
complaints. It should be recognized that the presence of food-specific IgG alone cannot be taken as
evidence of food allergy and only indicates immunologic sensitization by the food allergen in question.
This test should only be ordered by physicians who recognize the limitations of the test.
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
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CBC CBC with Differential, Blood
9109 Clinical Information: RBCs, WBCs, and platelets are produced in the bone marrow and released
into the peripheral blood. The primary function of the RBC is to deliver oxygen to tissues. WBCs are
key components of the immune system. Platelets play a vital role in blood clotting. Mean corpuscular
volume (MCV) is a measure of the size of the average RBC. Anemias are characterized as microcytic
(MCV <80), macrocytic (MCV >100), or normocytic. The red cell distribution width (RDW) is a
measure of the degree of variation in RBC size (anisocytosis). RDW may be helpful in distinguishing
between some anemias. For example, iron deficiency anemia is characterized by a high RDW, while
thalassemia is characterized by a low RDW.
Useful For: A screening tool to confirm a hematologic disorder, to establish or rule out a diagnosis,
to detect an unsuspected hematologic disorder, or to monitor effects of radiation or chemotherapy These
counts are used as clinical guides in the diagnosis or monitoring of many diseases
Interpretation: Results outside of normal value ranges may reflect a primary disorder of the
cell-producing organs or an underlying disease. Results should be interpreted in conjunction with the
patient's clinical picture and appropriate additional testing performed.
Reference Values:
RED BLOOD CELL COUNT (RBC)
Males:
Birth: 3.90-5.50 x 10(12)/L
1-7 days: 3.90-6.00 x 10(12)/L
8-14 days: 3.60-6.00 x 10(12)/L
15 days-1 month: 3.00-5.50 x 10(12)/L
2-5 months: 3.10-4.50 x 10(12)/L
6 months-1 year: 3.70-6.00 x 10(12)/L
2 years: 4.10-5.10 x 10(12)/L
3-5 years: 4.10-5.30 x 10(12)/L
6-11 years: 4.20-5.10 x 10(12)/L
12-15 years: 4.40-5.50 x 10(12)/L
Adults: 4.32-5.72 x 10(12)/L
Females:
Birth: 3.90-5.50 x 10(12)/L
1-7 days: 3.90-6.00 x 10(12)/L
8-14 days: 3.60-6.00 x 10(12)/L
15 days-1 month: 3.00-5.50 x 10(12)/L
2-5 months: 3.10-4.50 x 10(12)/L
6 months-1 year: 3.70-6.00 x 10(12)/L
2 years: 4.10-5.10 x 10(12)/L
3-5 years: 4.10-5.20 x 10(12)/L
6-11 years: 4.10-5.30 x 10(12)/L
12-15 years: 4.10-5.20 x 10(12)/L
Adults: 3.90-5.03 x 10(12)/L
HEMOGLOBIN
Males:
Birth-7 days: 13.5-22.0 g/dL
8-14 days: 12.5-21.0 g/dL
15 days-1 month: 10.0-20.0 g/dL
2-5 months: 10.0-14.0 g/dL
6 months-1 year: 10.5-13.5 g/dL
2 years: 11.0-14.0 g/dL
3-5 years: 11.0-14.5 g/dL
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6-11 years: 12.0-14.0 g/dL
12-15 years: 12.8-16.0 g/dL
Adults: 13.5-17.5 g/dL
Females:
Birth-7 days: 13.5-22.0 g/dL
8-14 days: 12.5-21.0 g/dL
15 days-1 month: 10.0-20.0 g/dL
2-5 months: 10.0-14.0 g/dL
6 months-1 year: 10.5-13.5 g/dL
2 years: 11.0-14.0 g/dL
3-5 years: 11.8-14.7 g/dL
6-11 years: 12.0-14.5 g/dL
12-15 years: 12.2-14.8 g/dL
Adults: 12.0-15.5 g/dL
HEMATOCRIT
Males:
Birth-7 days: 42.0-60.0%
8-14 days: 39.0-60.0%
15 days-1 month: 31.0-55.0%
2-5 months: 28.0-42.0%
6 months-1 year: 33.0-40.0%
2 years: 33.0-42.0%
3-5 years: 33.0-43.0%
6-11 years: 35.8-42.4%
12-15 years: 37.3-47.3%
Adults: 38.8-50.0%
Females:
Birth-7 days: 42.0-60.0%
8-14 days: 39.0-60.0%
15 days-1 month: 31.0-55.0%
2-5 months: 28.0-42.0%
6 months-1 year: 33.0-40.0%
2 years: 33.0-42.0%
3-5 years: 35.0-44.0%
6-11 years: 35.7-43.0%
12-15 years: 36.3-43.4%
Adults: 34.9-44.5%
PLATELETS
Birth-5 months: 150-350 x 10(9)/L
> or =6 months: 150-450 x 10(9)/L
NEUTROPHILS
Birth: 6.00-26.00 x 10(9)/L
1-7 days: 1.50-10.00 x 10(9)/L
8-14 days: 1.00-9.50 x 10(9)/L
15 days-1 month: 1.00-9.00 x 10(9)/L
2-5 months: 1.00-8.50 x 10(9)/L
6 months-5 years: 1.50-8.50 x 10(9)/L
6-11 years: 1.50-8.50 x 10(9)/L
12-15 years: 1.80-8.00 x 10(9)/L
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Adults: 1.70-7.00 x 10(9)/L
LYMPHOCYTES
Birth: 2.00-11.00 x 10(9)/L
1-14 days: 2.00-17.00 x 10(9)/L
15 days-1 month: 2.50-16.50 x 10(9)/L
2-5 months: 4.00-13.50 x 10(9)/L
6 months-11 months: 4.00-10.50 x 10(9)/L
1-5 years: 1.50-7.00 x 10(9)/L
6-11 years: 1.50-6.50 x 10(9)/L
12-15 years: 1.20-5.20 x 10(9)/L
Adults: 0.90-2.90 x 10(9)/L
MONOCYTES
Birth-14 days: 0.40-1.80 x 10(9)/L
15 days-11 months: 0.05-1.10 x 10(9)/L
1-15 years: 0.00-0.80 x 10(9)/L
Adults: 0.30-0.90 x 10(9)/L
EOSINOPHILS
Birth-5 months: 0.02-0.85 x 10(9)/L
6 months-11 months: 0.05-0.70 x 10(9)/L
1-5 years: 0.00-0.65 x 10(9)/L
6-15 years: 0.00-0.50 x 10(9)/L
Adults: 0.05-0.50 x 10(9)/L
BASOPHILS
Birth-5 months: 0.00-0.60 x 10(9)/L
6 months-15 years: 0.00-0.20 x 10(9)/L
> or =16 years: 0.00-0.30 x 10(9)/L
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context of the patient's clinical history and other diagnostic tests by a qualified pathologist.
Useful For: Aids in the diagnosis of hairy cell leukemia and marginal zone lymphomas
Interpretation: This test includes only technical performance of the stain (no pathologist
interpretation is performed). If diagnostic consultation by a pathologist is required, order 70012 /
Pathology Consultation. The positive and negative controls are verified as showing appropriate
immunoreactivity. If a control tissue is not included on the slide, a scanned image of the relevant quality
control tissue is available upon request; contact 855-516-8404. Interpretation of this test should be
performed in the context of the patient's clinical history and other diagnostic tests by a qualified
pathologist.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 435
60824 CD123, Immunostain Without Interpretation
Clinical Information: In normal lymphoid tissues, CD123 is expressed in plasmacytoid monocytes
and mast cells in interfollicular regions. In bone marrow, it is expressed in hematopoietic precursors, mast
cells and megakaryocytes. CD123 is part of the IL3 receptor complex, involved in cellular growth and
differentiation. Certain reactive lymph nodes show increased numbers of plasmacytoid monocytes, eg,
Kikuchis lymphadenitis. CD123 is characteristically expressed in blastic plasmacytoid dendritic cell
neoplasm, aiding in its distinction from acute monocytic leukemia.
Clinical References: 1. Sun Q, Woodcock JM, Rapoport A, et al: Monoclonal antibody 7G3
recognizes the N-terminal domain of the human interleukin-3 (IL-3) receptor alpha-chain and functions as
a specific IL-3 receptor antagonist. Blood 1996 Jan 1;87(1):83-92 2. Spener J, Diss TC, Isaacson PG: A
study of the properties of a low-grade mucosal B-cell lymphoma using a monoclonal antibody specific for
the tumour immunoglobulin. J Pathol 1990 Mar;160(3):231-238
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 436
a control tissue is not included on the slide, a scanned image of the relevant quality control tissue is
available upon request; contact 855-516-8404. Interpretation of this test should be performed in the
context of the patient's clinical history and other diagnostic tests by a qualified pathologist.
Clinical References: 1. Bayer-Garner IB, Sanderson RD, Dhodapkar MV, et al: Syndecan-1
(CD138) immunoreactivity in bone marrow biopsies of multiple myeloma: shed syndecan-1
accumulates in fibrotic regions. Mod Pathol 2001;14(10):1052-1058 2. Dunphy CH, Nies MK, Gabriel
DA. Correlation of plasma cell percetages by CD138 immunohistochemistry, cyclin D1 status, and
CD56 expression with clinical parameters and overall survival in plasma cell myeloma. Appl
Immunohistochem Mol Morphol 2007;15(3):248-254 3. Kambham N, Kond C, Longacre TA, et al:
Utility of syndecan-1 (CD138) expression in the diagnosis of undifferentiated malignant neoplasms: a
tissue microarray study of 1,754 cases. Appl Immunohistochem Mol Morphol 2005;13(4):304-310
Clinical References: 1. Grimm MC, Elsbury SK, Pavli P, Doe WF: Enhanced expression and
production of monocyte chemoattractant protein-1 in inflammatory bowel disease mucosa. J Leukoc
Biol 1996 Jun;59(6):804-812 2. Wright SD, Ramos RA, Tobias PS, et al: CD14, a receptor for
complexes of lipopolysaccharide (LPS) and LPS binding protein. Science 1990 Sep
21;249(4975):1431-1433
Clinical References: 1. Nguyen TT, Schwartz EF, West RB, et al: Expression of CD163
(hemoglobin scavenger receptor) in normal tissues, lymphomas, carcinomas, and sarcomas is largely
restricted to the monocyte/macrophage lineage. Am J Surg Pathol 2005 May;29(5):617-624 2. Lau SK,
Chun PG, Weiss LM: CD163: a specific marker of macrophages in paraffin-embedded tissue samples.
Am J Clin Pathol 2004 Nov;122(5):794-801
Useful For: Identification of normal and neoplastic B cells found during all stages of B-cell maturation
Interpretation: This test includes only technical performance of the stain (no pathologist interpretation
is performed). If diagnostic consultation by a pathologist is required, order 70012 / Pathology
Consultation. The positive and negative controls are verified as showing appropriate immunoreactivity. If
a control tissue is not included on the slide, a scanned image of the relevant quality control tissue is
available upon request; contact 855-516-8404. Interpretation of this test should be performed in the
context of the patient's clinical history and other diagnostic tests by a qualified pathologist.
Clinical References: 1. Masir N, Marafioti T, Jones M, et al: Loss of CD19 expression in B-cell
neoplasms. Histopathology 2006;48:239-246 2. Kirk CM, Lewin D, Lazarchick J, et al: Primary hepatic
B-cell lymphoma of mucosa-associated lymphoid tissue. Arch Pathol Lab Med 1999;123:716-719
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 438
Useful For: Marker of Langerhans cells and immature T cells
Interpretation: This test includes only technical performance of the stain (no pathologist
interpretation is performed). If diagnostic consultation by a pathologist is required, order 70012 /
Pathology Consultation. The positive and negative controls are verified as showing appropriate
immunoreactivity. If a control tissue is not included on the slide, a scanned image of the relevant quality
control tissue is available upon request; contact 855-516-8404. Interpretation of this test should be
performed in the context of the patient's clinical history and other diagnostic tests by a qualified
pathologist.
Clinical References: 1. Chang KC, Huang GC, Jones, D, et al: Distribution patterns of dendritic
cells and T cells in diffuse large B-cell lymphomas correlate with prognoses. Clin Cancer Res
2007;13:6666-6672 2. Lau SK, Chu PG, Weiss LM: Immunohistochemical expression of Langerin in
Langerhans cell histiocytosis and non-Langerhans cell histiocytic disorders. Am J Surg Pathol
2008;32(4):615-619 3. Perez L, Shurin MR, Collins B, et al: Comparative analysis of CD1a, S-100,
CD83, and CD11c human dendritic cells in normal, premalignant, and malignant tissues. Histol
Histopathol 2005;20:1165-1172
Clinical References: 1. Campbell AM, Peters SB, Zirwas MJ, et al: Immunophenotypic diagnosis
of primary cutaneous lymphomas. A review for the practicing dermatologist. J Clin Aesthet Dermatol
2010;3(10):21-25 2. Jordan JH, Walchshofer S, Jurecka W, et al: Immunohistochemical properties of
bone marrow mast cells in systemic mastocytosis: evidence for expression of CD2, CD117/Kit, and
bcl-x(L). Hum Pathol 2001;32(5):545-552 3. Went P, Agostinelli C, Gallamini A, et al: Marker
expression in peripheral T-cell lymphoma: a proposed clinical-pathologic prognostic score. J Clin Oncol
2006;24(16):2472-2479
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 439
2% of CVID patients and appears to be inherited as an autosomal recessive defect.(4) Since these
patients have normal numbers of B cells with absent CD19 expression on the cell surface (4), CD20 can
be used as a marker to help identify these patients. A contrasting situation exists for patients receiving
rituximab, ofatumumab, and other anti-CD20 monoclonal antibodies that are used to treat certain
cancers, autoimmune diseases, or for B-cell depletion to prevent humoral rejection in positive
crossmatch renal transplantation. These agents block available CD20-binding sites and, therefore, the
antibody used for this flow cytometric assay cannot recognize the CD20 molecule on B cells. The
concomitant use of the CD19 marker provides information on the extent of B-cell depletion when using
this particular treatment strategy. The absolute counts of lymphocyte subsets are known to be influenced
by a variety of biological factors, including hormones, the environment, and temperature. The studies on
diurnal (circadian) variation in lymphocyte counts have demonstrated progressive increase in CD4
T-cell count throughout the day, while CD8 T cells and CD19+ B cells increase between 8:30 am and
noon, with no change between noon and afternoon. Natural killer cell counts, on the other hand, are
constant throughout the day.(5) Circadian variations in circulating T-cell counts have been shown to be
negatively correlated with plasma cortisol concentration.(6-8) In fact, cortisol and catecholamine
concentrations control distribution and, therefore, numbers of naive versus effector CD4 and CD8 T
cells.(6) It is generally accepted that lower CD4 T-cell counts are seen in the morning compared with
the evening (9), and during summer compared to winter.(10) These data, therefore, indicate that timing
and consistency in timing of blood collection is critical when serially monitoring patients for
lymphocyte subsets.
Useful For: Evaluation of CD19 deficiency in patients with a suspected CD19 deficiency (humoral
immunodeficiency) Confirming complete absence of B cells in suspected primary humoral
immunodeficiencies using both CD19 and CD20 markers Assessing therapeutic B-cell depletion
quantitatively (absolute counts of cells/mcL) in any clinical context, including malignancies, autoimmune
diseases such as rheumatoid arthritis, systemic lupus erythematosus, and membranous glomerulonephritis
among others, and treatment or prevention of acute humoral rejection in positive crossmatch renal
transplant recipients This test is not useful for assessing whether B cells express the target molecule
(CD20) in the context of initiating therapeutic monoclonal anti-CD20 antibody therapy (rituximab,
ofatumumab, and tositumomab) for any of the hematological malignancies, or in other clinical contexts,
such as autoimmunity, instead order TAE / Therapeutic Antibody by Flow Cytometry.
Interpretation: The presence of CD20+ B cells with corresponding absence of CD19 staining in
individuals not receiving anti-CD20 monoclonal antibody treatment or with clinical features of variable
primary humoral immunodeficiency may suggest an underlying CD19 deficiency, which should be further
evaluated. Absence of both CD20 and CD19 markers on B cells in blood from individuals not on
anti-CD20 monoclonal antibody treatment is consistent with complete mature and immature peripheral
B-cell depletion, which may be due to an underlying primary immunodeficiency. Patients receiving B-cell
depleting therapy with anti-CD20 antibodies can show unusual populations of B cells on reconstitution
that express either CD19 or CD20 due to a phenomenon known as trogocytosis.
Reference Values:
%CD19 B CELLS
> or =19 years: 4.6-22.1%
CD19 ABSOLUTE
> or =19 years: 56.6-417.4 cells/mcL
%CD20 B CELLS
> or =19 years: 5.0-22.3%
CD20 ABSOLUTE
> or =19 years: 74.4-441.1 cells/mcL
CD45 ABSOLUTE
18-55 years: 0.99-3.15 thou/mcL
>55 years: 1.00-3.33 thou/mcL
Clinical References: 1. Nadler LM, Ritz J, Hardy R, et al: A unique cell-surface antigen identifying
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 440
lymphoid malignancies of B-cell origin. J Clin Invest 1981;67:134 2. Robillard N, Avet-Loiseau H,
Garand R, et al: CD20 is associated with a small mature plasma cell morphology and t(11;14) in multiple
myeloma. Blood 2003;102(3):1070-1071 3. Pescovitz MD: Rituximab, an anti-CD20 monoclonal
antibody: history and mechanism of action. Am J Transplant 2006;6:859-866 4. van Zelm MC, Reisli I,
van der Burg M, et al: An antibody-deficiency syndrome due to mutations in the CD19 gene. N Engl J
Med 2006;354:1901-1912 5. Carmichael KF, Abayomi A: Analysis of diurnal variation of lymphocyte
subsets in healthy subjects and its implication in HIV monitoring and treatment. 15th Intl Conference on
AIDS, Bangkok, Thailand, 2004, Abstract B11052 6. Dimitrov S, Benedict C, Heutling D, et al: Cortisol
and epinephrine control opposing circadian rhythms in T-cell subsets. Blood 2009 May
21;113(21):5134-5143 7. Dimitrov S, Lange T, Nohroudi K, Born J: Number and function of circulating
antigen presenting cells regulated by sleep. Sleep 2007;30:401-411 8. Kronfol Z, Nair M, Zhang Q, et al:
Circadian immune measures in healthy volunteers: relationship to hypothalamic-pituitary-adrenal axis
hormones and sympathetic neurotransmitters. Psychosom Med 1997;59:42-50 9. Malone JL, Simms TE,
Gray GC, et al: Sources of variability in repeated T-helper lymphocyte counts from HIV 1-infected
patients: total lymphocyte count fluctuations and diurnal cycle are important. J AIDS 1990;3:144-151 10.
Paglieroni TG, Holland PV: Circannual variation in lymphocyte subsets, revisited. Transfusion
1994;34:512-516
Clinical References: 1. Cartun RW, Coles FB, Pastuszak WT: Utilization of monoclonal antibody
L26 in the identification and confirmation of B-cell lymphomas. A sensitive and specific marker
applicable to formalin- and B5-fixed, paraffin-embedded tissues. Am J Pathol 1987;129(3):415-421 2
Kurtin PJ, Hobday KS, Ziesmer S, Caron BL: Demonstration of distinct antigenic profiles of small
B-cell lymphomas by paraffin section immunohistochemistry. Am J Clin Pathol 1999;112(3):319-329 3.
de Leon ED, Alkan S, Huang JC, Hsi ED: Usefulness of an immunohistochemical panel in
paraffin-embedded tissues for the differentiation of B-cell non-Hodgkins lymphomas of small
lymphocytes. Mod Pathol 1998;11(11):1046-1051 4. Martinez AE, Lin L, Dunphy CH: Grading of
follicular lymphoma: comparison of routine histology with immunohistochemistry. Arch Pathol Lab
Med 2007;131(7):1084-1088
Useful For: Identification of follicular dendritic cells and a subset of mantle zone lymphocytes
Interpretation: This test includes only technical performance of the stain (no pathologist
interpretation is performed). If diagnostic consultation by a pathologist is required, order 70012 /
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 441
Pathology Consultation. The positive and negative controls are verified as showing appropriate
immunoreactivity. If a control tissue is no included on the slide, the scanned image of the relevant
quality control tissue is available upon request; contact 855-516-8404. Interpretation of this test should
be performed in the context of the patients clinical history and other diagnostic tests by a qualified
pathologist.
Clinical References: 1. de Leval L, Harris NL, Longtine J, et al: Cutaneous B-cell lymphomas of
follicular and marginal zone types: use of Bcl-6, CD10, Bcl-2, and CD21 in differential diagnosis and
classification. Am J Surg Pathol 2001;25(6):732-741 2. Maeda K, Matsuda M, Suzuki H, et al:
Immunohistochemical recognition of human follicular dendritic cells (FDCs) in routinely processed
paraffin sections. J Histochem Cytochem 2002;50(11):1475-1485. 3. Mesquita RA, de Araujo VC, Paes
RAP, et al: Immunohistochemical analysis for CD21, CD35, caldesmon and S100 protein on dendritic
cells types in oral lymphomas. J Appl Oral Sci 2009;17(3):248-253 4. Nakamura S, Nagahama M,
Kagami Y, et al: Hodgkins disease expressing follicular dendritic cell marker CD21 without any
other B-cell marker: a clinicopathologic study of nine cases. Am J Surg Pathol 1999;23(4):363-376
Useful For: Identification of follicular dendritic cells and useful in the classification of low-grade
B-cell lymphomas
Interpretation: This test includes only technical performance of the stain (no pathologist interpretation
is performed). If diagnostic consultation by a pathologist is required, order 70012 / Pathology
Consultation. The positive and negative controls are verified as showing appropriate immunoreactivity. If
a control tissue is not included on the slide, a scanned image of the relevant quality control tissue is
available upon request; contact 855-516-8404. Interpretation of this test should be performed in the
context of the patient's clinical history and other diagnostic tests by a qualified pathologist.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 442
Clinical References: 1. Higgins RA, Blankenship JE, Kinney MC: Application of
immunohistochemistry in the diagnosis of non-Hodgkin and Hodgkin lymphoma. Arch Pathol Lab Med
2008;132(3):441-461 2. Kurtin PJ, Hobday KS, Ziesmer S, Caron BL: Demonstration of distinct
antigenic profiles of small B-cell lymphomas by paraffin section immunohistochemistry. Am J Clin
Pathol 1999;112(3):319-329 3. Linderoth J, Jerkeman M, Cavallin-Stahl E, et al: Immunohistochemical
expression of CD23 and CD40 may identify prognostically favorable subgroups of diffuse large B-cell
lymphoma: a Nordic lymphoma group study. Clin Cancer Res 2003;9:722-728
Useful For: Identification of follicular T helper cells and phenotyping of angioimmunoblastic T-cell
lymphoma
Interpretation: This test includes only technical performance of the stain (no pathologist
interpretation is performed). If diagnostic consultation by a pathologist is required, order 70012 /
Pathology Consultation. The positive and negative controls are verified as showing appropriate
immunoreactivity. If a control tissue is not included on the slide, a scanned image of the relevant quality
control tissue is available upon request; contact 855-516-8404. Interpretation of this test should be
performed in the context of the patient's clinical history and other diagnostic tests by a qualified
pathologist.
Clinical References: 1. Dorfman DM, Brown JA, Shahsafaie A, Freeman G: Programmed death-1
(PD-1) is a marker of geminal center-associated T cells and angioimmunoblastic T-cell lymphoma. Am
J Surg Pathol 2006 Jul;30(7):802-810 2. Roncador G, Garc-a Verdes-Montenegro JF, Tedoldi S, et al:
Expression of two markers of germinal center T cells (SAP and PD-1) in angioimmunoblastic T-cell
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 443
lymphoma. Haematologica 2007 Aug;92(8):1059-1066 3. Kobayashi M, Kawano S, Hatachi S, et al:
Enhanced expression of programmed death-1 (PD-1)/PD-L1 in salivary glands of patients with
Sjogren's Syndrome. J Rheumatol 2005 Nov;32(11):2156-2163
Clinical References: 1. Oudejans JJ, van der Valk P: Immunohistochemical classification of T cell
and NK cell neoplasms. J Clin Pathol 2002;55(2):892 2. Steward M, Bishop R, Piggott NH, et al:
Production and characterization of a new monoclonal antibody effective in recognizing the CD3 T-cell
associated antigen in formalin-fixed embedded tissue. Histopathology 1997;30(1):16-22 3. Went P,
Agostinelli C, Gallamini A, et al: Marker expression in peripheral T-cell lymphoma: a proposed
clinical-pathologic prognostic score. J Clin Oncol 2006;24(16):2472-2479
Clinical References: 1. Barry T, Jaffe ES, Sorbara L. et al: Peripheral T-cell lymphomas expressing
CD30 and CD15. Am J Surg Pathol 2003;27(12):1513-1522 2. Jaffe ES: Anaplastic large cell lymphoma:
the shifting sands of diagnostic hematopathology. Mod Pathol 2001;14(3):219-228 3. Sabattini E, Pizzi
M, Tabanelli V, et al: CD30 expression in peripheral T-cell lymphomas. Haematologica
2013;98(8):e81-e82
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 444
near the epithelial borders. Diagnostically, CD31 expression can confirm a diagnosis of angiosarcoma, a
neoplasm of endothelial cells.
Clinical References: 1. Jilani I, Estey E, Huh Y, et al: Differences in CD33 intensity between
various myeloid neoplasms. Am J Clin Pathol 2002 Oct;118(4):560-566 2. Thalhammer-Scherrer R,
Mitterbauer G, Simonitsch I, et al: The immunophenotype of 325 adult acute leukemias: relationship to
morphologic and molecular classification and molecular classification and proposal for a minimal
screening program highly predictive for lineage discrimination. Am J Clin Pathol 2002
Mar;117(3):380-389
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 445
in the setting of acute myeloid leukemia or B lymphoblastic leukemia. It is also useful in the
classification of spindle cell neoplasms (gastrointestinal stromal tumors, solitary fibrous tumors, and
angiosarcomas are often positive).
Useful For: A marker of hematopoietic progenitor cells and vascular endothelial cells Classification of
spindle cell neoplasms
Interpretation: This test includes only technical performance of the stain (no pathologist interpretation
is performed). If diagnostic consultation by a pathologist is required, order 70012 / Pathology
Consultation. The positive and negative controls are verified as showing appropriate immunoreactivity. If
a control tissue is not included on the slide, a scanned image of the relevant quality control tissue is
available upon request; contact 855-516-8404. Interpretation of this test should be performed in the
context of the patient's clinical history and other diagnostic tests by a qualified pathologist.
Clinical References: 1. Biddle DA, Jae YR, Yoon GS, et al: Extranodal follicular dendritic cell
sarcoma of the head and neck region: three new cases, with a review of the literature. Mod Pathol 2002
Jan;15(1):50-58 2. Maeda K, Matsuda M, Suzuki H, et al: Immunohistochemical recognition of human
follicular dendritic cells (FDCs) in routinely processed paraffin sections. J Histochem Cytochem
2002;50(11):1475-1485 3. Mesquita RA, de Araujo VC, Paes RA, et al: Immunohistochemical analysis
for CD21, CD35, Caldesmon and S100 protein on dendritic cells types in oral lymphomas. J Appl Oral
Sci 2009;17(3):248-253
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 446
Useful For: Classification of lymphoproliferative and plasma cell proliferative disorders
Interpretation: This test includes only technical performance of the stain (no pathologist
interpretation is performed). If diagnostic consultation by a pathologist is required, order 70012 /
Pathology Consultation. The positive and negative controls are verified as showing appropriate
immunoreactivity. If a control tissue is not included on the slide, a scanned image of the relevant quality
control tissue is available upon request; contact 855-516-8404. Interpretation of this test should be
performed in the context of the patient's clinical history and other diagnostic tests by a qualified
pathologist.
Clinical References: 1. Zupo S, Rugari E, Dono M, et al: CD38 signaling by agonistic monoclonal
antibody prevents apoptosis of human germinal center B cells. Eur J Immunol 1994;24:1218-1222 2.
Rodig SJ, Vergilio JA, Shahsafaei A, et al: Characteristic expression patterns of TCL1, CD38, and
CD44 identify aggressive lymphomas harboring a MYC translocation. Am J Surg Pathol 2008
Jan;32(1):113-122 3. Soma LA, Craig FE, Swerdlow SH: The proliferation center microenvironment
and prognostic markers in chronic lymphocytic leukemia/small lymphocytic lymphoma. Hum Pathol
2006 Feb;37(2):152-159
Useful For: Serial monitoring of CD4 T cell count in HIV-positive patients Useful for follow-up and
diagnostic evaluation of primary cellular immunodeficiencies, including severe combined
immunodeficiency T-cell immune monitoring following immunosuppressive therapy for
transplantation, autoimmunity, and other immunological conditions where such treatment is utilized
Assessment of T-cell immune reconstitution post hematopoietic cell transplantation Early screening of
gross quantitative anomalies in T cells in infection or malignancies
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 447
Interpretation: HIV treatment guidelines from the US Department of Health and Human Services and
the International Antiviral Society USA Panel recommend antiviral treatment in all patients with HIV
infection, regardless of CD4 T-cell count.(7,8) Additionally, antibiotic prophylaxis for Pneumocystis
jiroveci infection and other opportunistic infections is recommended for patients with CD4 count <200
cells/mcL.
Reference Values:
The appropriate age-related reference values will be provided on the report.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 448
Useful For: Serial monitoring of CD4 T-cell count in HIV-positive patients Follow-up and
diagnostic evaluation of primary cellular immunodeficiencies, including severe combined
immunodeficiency T-cell immune monitoring following immunosuppressive therapy for
transplantation, autoimmunity, and other immunological conditions where such treatment is utilized
Assessment of T-cell immune reconstitution post hematopoietic cell transplantation Early screening of
gross quantitative anomalies in T cells in infection or malignancies
Interpretation: HIV treatment guidelines from the US Department of Health and Human Services
and the International Antiviral Society-USA Panel recommend antiviral treatment in all patients with
HIV infection, regardless of CD4 T-cell count.(7,8) Additionally, antibiotic prophylaxis for
Pneumocystis jiroveci infection and other opportunistic infections is recommended for patients with
CD4 count <200 cells/mcL.
Reference Values:
The appropriate age-related reference values will be provided on the report.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 449
cellular immunodeficiency associated with other congenital problems including cardiac defects, facial
dysmorphism, hypoparathyroidism, and secondary hypocalcemia, and chromosome 22q11.2 deletion (in
a significant proportion of patients)--measurement of thymic function provides valuable information on
the functional phenotype, ie, complete DGS (associated with thymic aplasia in a minority of patients) or
partial DGS (generally well-preserved thymic function seen the in the majority of patients). Thymus
transplants have been performed in patients with complete DGS, but are typically not required in partial
DGS. There can be change in peripheral T-cell counts in DGS patients with age.
Useful For: Evaluating thymic reconstitution in patients following hematopoietic cell transplantation,
chemotherapy, immunomodulatory therapy, and immunosuppression Evaluating thymic recovery in
HIV-positive patients on highly active antiretroviral therapy Evaluating thymic output in patients with
DiGeorge syndrome or other cellular immunodeficiencies Assessing the naive T-cell compartment in a
variety of immunological contexts (autoimmunity, cancer, immunodeficiency, and transplantation)
Identification of thymic remnants postthymectomy for malignant thymoma or as an indicator of relapse of
disease (malignant thymoma) or other contexts of thymectomy
Interpretation: The absence or reduction of CD31+CD4 recent thymic emigrants (RTEs) generally
correlates with loss or reduced thymic output and changes in the naive CD4 T-cell compartment,
especially in infancy and prepubertal children. The CD4RTE result has to be interpreted more cautiously
in adults due to age-related decline in thymic function and correlated with total CD4 T cell count and
other relevant immunological data. CD4 RTEs measured along with TREC (TREC / T-Cell Receptor
Excision Circles (TREC) Analysis, Blood) provides a comprehensive assessment of thymopoiesis, but
should not be used in adults over the sixth decade of life as clinically meaningful information on thymic
function is limited in the older population due to a physiological decline in thymic activity. To evaluate
immune reconstitution or recovery of thymopoiesis post-T-cell depletion due to posthematopoietic cell
transplant, immunotherapy, or other clinical conditions, it is helpful to systematically (serially) measure
CD4RTE, and TREC copies in the appropriate age groups.
Reference Values:
CD4 ABSOLUTE
Males
1 month-17 years: 153-1,745 cells/mcL
18-70 years: 290-1,175 cells/mcL
Reference values have not been established for patients that are <30 days of age.
Reference values have not been established for patients that are >70 years of age.
Females
1 month-17 years: 582-1,630 cells/mcL
18-70 years: 457-1,766 cells/mcL
Reference values have not been established for patients that are <30 days of age.
Reference values have not been established for patients that are >70 years of age.
CD4 RTE %
Males
1 month-17 years: 19.4-60.9%
18-25 years: 6.4-51.0%
26-55 years: 6.4-41.7%
> or =56 years: 6.4-27.7%
Reference values have not been established for patients that are <30 days of age.
Reference values have not been established for patients that are >70 years of age.
Females
1 month-17 years: 25.8-68.0%
18-25 years: 6.4-51.0%
26-55 years: 6.4-41.7%
> or =56 years: 6.4-27.7%
Reference values have not been established for patients that are <30 days of age.
Reference values have not been established for patients that are >70 years of age.
Clinical References: 1. Grogg KL, Jung S, Erickson LA, et al: Primary cutaneous CD4-positive
small/medium-sized pleomorphic T-cell lymphoma: a clonal T-cell lymphoproliferative disorder with
indolent behavior. Mod Pathol 2008;21:708-715 2. Hans CP, Weisenburger DD, Greiner TC, et al:
Confirmation of the molecular classification of diffuse large B-cell lymphoma by
immunohistochemistry using a tissue microarray. Blood 2004;103(1):275-282 3. Oudejans JJ, van der
Valk P: Immunohistochemical classification of T cell and NK cell neoplasms. J Clin Pathol
2002;55(2):892 4. Went P, Agostinelli C, Gallamini A, et al: Marker expression in peripheral T-cell
lymphoma: a proposed clinical-pathologic prognostic score. J Clin Oncol 2006;24(16):2472-2479
Interpretation: This test includes only technical performance of the stain (no pathologist
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 451
interpretation is performed). If diagnostic consultation by a pathologist is required, order 70012 /
Pathology Consultation. The positive and negative controls are verified as showing appropriate
immunoreactivity. If a control tissue is not included on the slide, a scanned image of the relevant quality
control tissue is available upon request; contact 855-516-8404. Interpretation of this test should be
performed in the context of the patient's clinical history and other diagnostic tests by a qualified
pathologist.
Clinical References: 1. de Leon ED, Alkan S, Huang JC, Hsi ED: Usefulness of an
immunohistochemical panel in paraffin-embedded tissues for the differentiation of B-cell
non-Hodgkins lymphomas of small lymphocytes. Mod Pathol 1998;11(11):1046-1051 2. Kurtin PJ,
Hobday KS, Ziesmer S, Caron BL: Demonstration of distinct antigenic profiles of small B-cell
lymphomas by paraffin section immunohistochemistry. Am J Clin Pathol 1999;112(3):319-329 3. Lai R,
Weiss LM, Chang KL, Arber DA: Frequency of CD43 expression in non-Hodgkin lymphoma. A survey
of 742 cases and further characterization of rare CD43+ follicular lymphomas. Am J Clin Pathol
1999;111(4):488-494
Useful For: An aid in the identification of tumors with neuroendocrine differentiation An aid in the
identification of natural killer cell lineage in a subset of lymphomas
Interpretation: This test includes only technical performance of the stain (no pathologist
interpretation is performed). If diagnostic consultation by a pathologist is required, order 70012 /
Pathology Consultation. The positive and negative controls are verified as showing appropriate
immunoreactivity. If a control tissue is not included on the slide, a scanned image of the relevant quality
control tissue is available upon request; contact 855-516-8404. Interpretation of this test should be
performed in the context of the patient's clinical history and other diagnostic tests by a qualified
pathologist.
Clinical References: 1. Chu PG, Arber DA, Weiss LM: Expression of T/NK-cell and plasma cell
antigens in nonhematopoietic epithelioid neoplasms. An immunohistochemical study of 447 cases. Am
J Clin Pathol 2003;120:64-70 2. EL Demellawy D, Nasr AL, Babay S, Alowami S: Diagnostic utility of
CD56 immunohistochemistry in papillary carcinoma of the thyroid. Pathol Res Pract 2009;205:303-309
3. Kaufmann O, Georgi T, Dietel M: Utility of 123C3 monoclonal antibody against CD56 (NCAM) for
the diagnosis of small cell carcinomas on paraffin sections. Hum Pathol 1997;28(12):1373-1378 4.
Tsang WY, Chan JK, Ng CS, Pau MY: Utility of a paraffin section-reactive CD56 antibody (123C3) for
characterization and diagnosis of lymphomas. Am J Surg Pathol 1996;20(2):202-210
Useful For: Marker of natural killer cells and a subset of follicular T helper cells An aid in the
identification of tumors of neuroectodermal origin
Interpretation: This test includes only technical performance of the stain (no pathologist
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 453
interpretation is performed). If diagnostic consultation by a pathologist is required, order 70012 /
Pathology Consultation. The positive and negative controls are verified as showing appropriate
immunoreactivity. If a control tissue is not included on the slide, a scanned image of the relevant quality
control tissue is available upon request; contact 855-516-8404. Interpretation of this test should be
performed in the context of the patient's clinical history and other diagnostic tests by a qualified
pathologist.
Interpretation: This test includes only technical performance of the stain (no pathologist interpretation
is performed). If diagnostic consultation by a pathologist is required, order 70012 / Pathology
Consultation. The positive and negative controls are verified as showing appropriate immunoreactivity. If
a control tissue is not included on the slide, a scanned image of the relevant quality control tissue is
available upon request; contact 855-516-8404. Interpretation of this test should be performed in the
context of the patient's clinical history and other diagnostic tests by a qualified pathologist.
Clinical References: 1. Dolan MM, Singleton TP, Neglia J, Cioc A: Aplastic anemia and monosomy
7-associated dysmegakoaryocytopoiesis. Am J Clin Pathol 2006;126:925-930 2. Goldman BL, Wurzel J:
Hematopoiesis/erythropoiesis in myocardial infarcts. Mod Pathol 2001;14(6):589-594 3. Thiele J, von
Ammers E, Wanger S, et al: Megakaryocytopoiesis in idiopathic thrombocytopenic purpura: a
morphometric and immunohistochemical study on bone marrow biopsies with special emphasis on
precursor cells. Hematol Pathol 1991;5(2):75-82
Useful For: An aid in the identification of histocytic and myeloid lineage cells
Interpretation: This test includes only technical performance of the stain (no pathologist interpretation
is performed). If diagnostic consultation by a pathologist is required order 70012 / Pathology
Consultation. The positive and negative controls are verified as showing appropriate immunoreactivity. If
a control tissue is not included on the slide, a scanned image of the relevant quality control tissue is
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 454
available upon request. Please contact 1-855-516-8404. Interpretation of this test should be performed in
the context of the patient's clinical history and other diagnostic tests by a qualified pathologist.
Interpretation: This test includes only technical performance of the stain (no pathologist
interpretation is performed). If diagnostic consultation by a pathologist is required order 70012 /
Pathology Consultation. The positive and negative controls are verified as showing appropriate
immunoreactivity. If a control tissue is not included on the slide, a scanned image of the relevant quality
control tissue is available upon request. Please contact 1-855-516-8404. Interpretation of this test should
be performed in the context of the patient's clinical history and other diagnostic tests by a qualified
pathologist.
Useful For: An aid in the identification of T cells and natural killer cells
Interpretation: This test includes only technical performance of the stain (no pathologist
interpretation is performed). If diagnostic consultation by a pathologist is required order 70012 /
Pathology Consultation. The positive and negative controls are verified as showing appropriate
immunoreactivity. If a control tissue is not included on the slide, a scanned image of the relevant quality
control tissue is available upon request. Please contact 1-855-516-8404. Interpretation of this test should
be performed in the context of the patient's clinical history and other diagnostic tests by a qualified
pathologist.
Clinical References: 1. Chu PG, Arber DA, Weiss LM: Expression of T/NK-cell and plasma cell
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 455
antigens in non hematopoietic epithelioid neoplasms. An Immunohistochemical Study of 447 Cases.
Am J Clin Pathol 2003;120:64-70 2. Dunphy CH: Applications of flow cytometry and
immunohistochemistry to diagnostic hematopathology. Arch Pathol Lab Med 2004;128:1004-1022 3.
Higgins RA, Blankenship JE, Kinney MC: Application of immunohistochemistry in the diagnosis of
non-Hodgkin and Hodgkin lymphoma. Archives of Pathology and Laboratory Medicine
2008;132(3):441-461
Clinical References: 1. Dong HY, Wilkes S, Yang H: CD71 is selectively and ubiquitously
expressed at high levels in erythroid precursors of all maturation stages: A comparative immunochemical
study with glycophorin A and hemoglobin A. Am J Surg Pathol 2011 May;35(5):723-732 2. Marsee DK,
Pinkus GS, Yu H: CD71 (transferrin receptor): an effective marker for erythroid precursors in bone
marrow biopsy specimens. Am J Clin Pathol 2010;134:429-435 3. Sokmensuer LK, Muftuoglu S, Asan E:
Immunohistochemical analysis of CD71, CD98 and CD99 activation antigens in human palatine and
nasopharyngeal tonsils. Saudi Med J 2005;26(3):385-389
Clinical References: 1. Adams H, Liebisch P, Schmid P, et al: Diagnositc utility of B-cell lineage
markers CD20, CD791, PAX5, and CD19 in paraffin-embedded tissues From lymphoid neoplasms.
Applied Immunohistochemistry and Molecular Morphology 2009;17(2):96-101 2. Hashimoto M,
Yamashita Y, Mori N: Immunohistochemical detection of CD79a expression in precursor T cell
lymphoblastic lymphoma/leukaemias. Journal of Pathology 2002;197:341-347 3. Kurtin PJ, Hobday KS,
Ziesmer S, Caron BL: Demonstration of distinct antigenic profiles of small B-cell lymphomas by paraffin
section immunohistochemistry. Am J Clin Pathol 1999;112(3):319-329
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 456
GLICP CD8 T-Cell Immune Competence Panel, Global
89369 Clinical Information: CD8 T cells play an important role in the immune response to viral or
intracellular infectious agents, as well as antitumor immunity and immune surveillance. Upon
activation, CD8 T cells mediate a variety of effector functions, including cytokine secretion and
cytotoxicity. Interferon-gamma (IFN-gamma) is one of the early cytokines produced by CD8 T cells; it
is released within a few hours of activation.(1) The cytotoxic function is mediated by the contents of the
cytolytic granules.(1) Cell-surface mobilization of the cytolytic granule components, CD107a and
CD107b, also known as lysosome-associated membrane proteins LAMP-1 and LAMP-2, occurs when
CD8 T cells mediate their cytolytic function and degranulate.(2) CD8 T-cell activation occurs either
through the T-cell receptor-peptide-Major-Histo Compatibility Complex or by use of a mitogen (eg,
phorbol myristate acetate and the calcium ionophore ionomycin). Mitogen-mediated activation is
antigen nonspecific. Impairment of global CD8 T-cell activation (due to inherent cellular
immunodeficiency or as a consequence of over-immunosuppression by therapeutic agents) results in
reduced production of IFN-gamma and other cytokines, reduced cytotoxic function, and increased risk
for developing infectious complications. Agents associated with over-immunosuppression include the
calcineurin inhibitors (eg, cyclosporine A, FK506 [Prograf/tacrolimus], and rapamycin [sirolimus]),
antimetabolites (eg, mycophenolate mofetil), and thymoglobulin. Immunosuppression is most
commonly used for allograft maintenance in solid-organ transplant recipients, to prevent
graft-versus-host disease in allogeneic hematopoietic stem cell transplant patients and to treat patients
with autoimmune diseases. In these settings, reducing the risk for developing infectious complications
as a result of over-immunosuppression is a clinical challenge. Therapeutic drug monitoring is routinely
used in the transplant practice to avoid overtreatment and to determine patient compliance. But, the
levels of drugs measured in blood do not directly correlate with the administered dose due to individual
pharmacokinetic differences.(3) Furthermore, drug levels may not necessarily correlate with biological
activity of the drug. Consequently, it may be beneficial to consider modification of the
immunosuppression regimen based on the patient's level of functional immune competence. This assay
provides a means to evaluate over-immunosuppression within the CD8 T-cell compartment (global CD8
T-cell function). Intracellular IFN-gamma expression is a marker for CD8 T-cell activation. Surface
CD107a and CD107b are markers for cytotoxic function. This test may be most useful when ordered at
the end of induction immunosuppression and 2 to 3 months after maintenance immunosuppression to
ensure that global CD8 T-cell function is not compromised. The test may also provide value when
immunosuppression is increased to halt or prevent graft rejection, to provide information on a balance
between over-immunosuppression with subsequent infectious comorbidities and
under-immunosuppression with resultant graft rejection. The absolute counts of lymphocyte subsets are
known to be influenced by a variety of biological factors, including hormones, the environment and
temperature. The studies on diurnal (circadian) variation in lymphocyte counts have demonstrated
progressive increase in CD4 T-cell count throughout the day, while CD8 T cells and CD19+ B cells
increase between 8.30 a.m. and noon with no change between noon and afternoon. Natural killer-cell
counts, on the other hand, are constant throughout the day.(4) Circadian variations in circulating T-cell
counts have been shown to be negatively correlated with plasma cortisol concentration.(5-7) In fact,
cortisol and catecholamine concentrations control distribution and therefore, numbers of naive versus
effector CD4 and CD8 T cells.(5) It is generally accepted that lower CD4 T-cell counts are seen in the
morning compared to the evening(8) and during summer compared to winter.(9) These data therefore
indicate that timing and consistency in timing of blood collection is critical when serially monitoring
patients for lymphocyte subsets.
Useful For: Determining over immunosuppression within the CD8 T-cell compartment, when used
on transplant recipients and patients with autoimmune disorders receiving therapy with
immunosuppressant agents
Interpretation: Interferon-gamma (IFN-gamma) and CD107a and CD107b expression below the
defined reference range are consistent with a global impairment in CD8 T-cell function, most likely due
to over immunosuppression. IFN-gamma and CD107a and CD107b levels greater than the defined
reference range are unlikely to have any clinical significance.
Reference Values:
The appropriate age-related reference values will be provided on the report.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 457
Clinical References: 1. Betts MR, Casaza JP, Patterson BA, et al: Putative immunodominant human
immunodeficiency virus-specific CD8 T-cell responses cannot be predicted by MHC class I haplotype. J
Virol 2000;74:9144-9151 2. Peters PJ, Borst J, Oorschot V, et al: Cytotoxic T-lymphocyte granules are
secretory lysosomes, containing both perforin and granzymes. J Exp Med 1991;173:1099-1109 3.
Venkataramanan R, Shaw LM, Sarkozi L, et al: Clinical utility of monitoring tacrolimus blood
concentrations in liver transplant patients. J Clin Pharmacol 2001;41:542-551 4. Carmichael KF,
Abayomi A: Analysis of diurnal variation of lymphocyte subsets in healthy subjects and its implication in
HIV monitoring and treatment. 15th Intl Conference on AIDS, Bangkok, Thailand, 2004, Abstract #
B11052 5. Dimitrov S, Benedict C, Heutling D, et al: Cortisol and epinephrine control opposing circadian
rhythms in T-cell subsets. Blood 2009;113:5134-5143 6. Dimitrov S, Lange T, Nohroudi K, Born J:
Number and function of circulating antigen presenting cells regulated by sleep. Sleep 2007;30:401-411 7.
Kronfol Z, Nair M, Zhang Q, et al: Circadian immune measures in healthy volunteers: relationship to
hypothalamic-pituitary-adrenal axis hormones and sympathetic neurotransmitters. Pyschosom Med
1997;59:42-50 8. Malone JL, Simms TE, Gray GC, et al: Sources of variability in repeated T-helper
lymphocyte counts from HIV 1-infected patients: total lymphocyte count fluctuations and diurnal cycle
are important. J AIDS 1990;3:144-151 9. Paglieroni TG, Holland PV: Circannual variation in lymphocyte
subsets, revisited. Transfusion 1994;34:512-516
Useful For: Determining overimmunosuppression within the CD8 T-cell compartment, when used on
transplant recipients and patients with autoimmune disorders receiving therapy with immunosuppressant
agents
Interpretation: Interferon-gamma (IFN-gamma) and CD107a and CD107b expression below the
defined reference range are consistent with a global impairment in CD8 T-cell function, most likely due
to overimmunosuppression. IFN-gamma and CD107a and CD107b levels greater than the defined
reference range are unlikely to have any clinical significance.
Reference Values:
Interferon-gamma (IFN-gamma) expression (as % CD8 T cells): 10.3-56.0%
Reference values have not been established for patients who are <19 years of age.
Clinical References: 1. Betts MR, Casaza JP, Patterson BA, et al: Putative immunodominant
human immunodeficiency virus-specific CD8 T-cell responses cannot be predicted by MHC class I
haplotype. J Virol. 2000 Oct;74(19):9144-9151 2. Peters PJ, Borst J, Oorschot V, et al: Cytotoxic
T-lymphocyte granules are secretory lysosomes, containing both perforin and granzymes. J Exp Med.
1991 May 1;173(5):1099-1109 3. Venkataramanan R, Shaw LM, Sarkozi L, et al: Clinical utility of
monitoring tacrolimus blood concentrations in liver transplant patients. J Clin Pharmacol 2001
May;41(5):542-551 4. Carmichael KF, Abayomi A: Analysis of diurnal variation of lymphocyte subsets
in healthy subjects and its implication in HIV monitoring and treatment. 15th Intl Conference on AIDS,
Bangkok, Thailand, 2004, Abstract # B11052 5. Dimitrov S, Benedict C, Heutling D, et al: Cortisol and
epinephrine control opposing circadian rhythms in T-cell subsets. Blood 2009;113:5134-5143 6.
Dimitrov S, Lange T, Nohroudi K, Born J: Number and function of circulating antigen presenting cells
regulated by sleep. Sleep 2007;30:401-411 7. Kronfol Z, Nair M, Zhang Q, et al: Circadian immune
measures in healthy volunteers: relationship to hypothalamic-pituitary-adrenal axis hormones and
sympathetic neurotransmitters. Pyschosom Med 1997;59:42-50 8. Malone JL, Simms TE, Gray GC, et
al: Sources of variability in repeated T-helper lymphocyte counts from HIV 1-infected patients: total
lymphocyte count fluctuations and diurnal cycle are important. J AIDS 1990;3:144-151 9. Paglieroni
TG, Holland PV: Circannual variation in lymphocyte subsets, revisited. Transfusion 1994;34:512-516
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 459
Clinical References: 1. Chu PG, Arber DA, Weiss LM: Expression of T/NK-cell and plasma cell
antigens in non hematopoietic epithelioid neoplasms. An Immunohistochemical Study of 447 Cases. Am J
Clin Pathol 2003;120:64-70 2. Higgins RA, Blankenship JE, Kinney MC: Application of
immunohistochemistry in the diagnosis of non-Hodgkin and Hodgkin lymphoma. Archives of Pathology
and Laboratory Medicine 2008;132(3):441-461 3. Oudejans JJ, van der Valk P: Immunohistochemical
classification of T cell and NK cell neoplasms. J Clin Pathol 2002;55(2):892
Clinical References: 1. Choi YL, Chi JG, Suh YL: CD99 Immunoreactivity in ependymoma.
Applied Immunohistochemistry and Molecular Morphology 2001;9(2):125-129 2. Granter SR, Renshaw
AA, Fletcher CDM, et al: CD99 reactivity in mesenchymal chondrosarcoma. Human Pathology
1996;27(12):1273-1276 3. Lucas DR, Bentley G, Dan ME, et al: Ewing sarcoma vs. lymphoblastic
lymphoma. Am J Clin Pathol 2001;115:11-17
Useful For: Confirmation of suspected clinical diagnosis of hereditary diffuse gastric cancer
Identification of familial CDH1 mutation to allow for predictive testing in family members
Interpretation: All detected alterations are evaluated according to American College of Medical
Genetics recommendations.(1) Variants are classified based on known, predicted, or possible
pathogenicity and reported with interpretive comments detailing their potential or known significance.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 460
standards of interpretation and reporting of sequence variations: revisions 2007. Genet Med
2008:10(4):294-300 2. Lindor NM, McMaster ML, Lindor CJ, et al: Concise handbook of familial cancer
susceptibility syndromes. Second edition. J Natl Cancer Inst Monogr 2008;(38):1-93 3. Fitzgerald RC,
Hardwick R, Huntsman D, et al: Hereditary diffuse gastric cancer: updated consensus guidelines for
clinical management and directions for future research. J Med Genet 2010;47:436-444 4. Kaurah P,
Huntsman DG: Hereditary Diffuse Gastric Cancer. GeneReviews 2011. Available from URL:
http://www.ncbi.nlm.nih.gov/books/NBK1139/
Interpretation: All detected alterations are evaluated according to American College of Medical
Genetics and Genomics (ACMG) recommendations.(1) Variants are classified based on known,
predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or
known significance.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for
standards for interpretation and reporting of sequence variations: Revisions 2007. Genet Med 2008
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 461
Apr;10(4):294-300 2. DeBaun MR, Niemitz EL, McNeil DE, et al: Epigenetic alterations of H19 and
LIT1 distinguish patients with Beckwith-Wiedemann Syndrome with cancer and birth defects. Hum
Genet 2002;70:604-611 3. Choufani S, Shuman C, Weksberg R: Beckwith-Wiedemann Syndrome. Am
J of Med Genet 2010;154C:343-354 4. Romanelli V, Belinchon A, Benito-Sanz S, et al: CDKN1C
(p57[Kip2]) Analysis in Beckwith-Wiedemann Syndrome (BWS) Patients: Genotype-Phenotype
Correlations, Novel Mutations, and Polymorphisms. Am J of Med Genet Part A 2010;152A:1390-1397
5. Lam WWK, Hatada I, Ohishi S, et al: Analysis of germline CDKNIC (p57[Kip2]) mutations in
familial and sporadic Beckwith-Wiedemann syndrome (BWS) provides a novel genotype-phenotype
correlation. J Med Genet 1999;36:518-523 6. Arboleda VA, Lee H, Parnaik R, et al: Mutations in the
PCNA-binding domain of CDKN1C cause IMAGe syndrome. Nature Genetics 2012;44(7):788-792
Clinical References: 1. Moskaluk CA, Zhang H, Powell SM, et al: Cdx2 protein expression in
normal and malignant human tissues: An Immunohistochemical Survey Using Tissue Microarrays.
Modern Pathology 2003;16(9):913-919 2. Park SY, Kim SH, Kim JH, et al: Panels of
immunohistochemical markers help determine primary sites of metastatic adenocarcinoma. Archives of
Pathology and Laboratory Medicine 2007;131(10):1561-1567 3. Werling RW, Yaziji H, Bacchi CE,
Gown AM: CDX2, a highly sensitive and specific marker of adenocarcinomas of intestinal origin: An
Immunohistochemical Survey of 476 Primary and Metastatic Carcinomas. Am J Surg Pathol
2003;27(3):303-310
Useful For: Initial evaluation of acute myeloid leukemia, both for assigning an appropriate diagnostic
subclassification and as an aid for determining prognosis.
Interpretation: The results will be given as positive or negative for CEBPA mutation and, if positive,
the mutation will be described and single or double mutation status will be indicated.
Reference Values:
An interpretive report will be provided
Reference Values:
<0.35 kU/L
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 463
Saunders Company, New York, 2007, Part VI, pp 961-971
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical utility
of food-specific IgG tests has not been established. These tests can be used in special clinical situations to
select foods for evaluation by diet elimination and challenge in patients who have food-related
complaints. It should be recognized that the presence of food-specific IgG alone cannot be taken as
evidence of food allergy and only indicates immunologic sensitization by the food allergen in question.
This test should only be ordered by physicians who recognize the limitations of the test.
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 464
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Reference Values:
An interpretive report will be provided.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 465
CDCOM Celiac Disease Comprehensive Cascade
89201 Clinical Information: Celiac disease (gluten-sensitive enteropathy, celiac sprue) results from an
immune-mediated inflammatory process following ingestion of wheat, rye, or barley proteins that occurs
in genetically susceptible individuals.(1) The inflammation in celiac disease occurs primarily in the
mucosa of the small intestine, which leads to villous atrophy.(1) Common clinical manifestations related
to gastrointestinal inflammation include abdominal pain, malabsorption, diarrhea, and constipation.(2)
Clinical symptoms of celiac disease are not restricted to the gastrointestinal tract. Other common
manifestations of celiac disease include failure to grow (delayed puberty and short stature), iron
deficiency, recurrent fetal loss, osteoporosis, chronic fatigue, recurrent aphthous stomatitis (canker sores),
dental enamel hypoplasia, and dermatitis herpetiformis.(3) Patients with celiac disease may also present
with neuropsychiatric manifestations including ataxia and peripheral neuropathy, and are at increased risk
for development of non-Hodgkin lymphoma.(1,2) The disease is also associated with other clinical
disorders including thyroiditis, type I diabetes mellitus, Down syndrome, and IgA deficiency.(1,3) Celiac
disease tends to occur in families; individuals with family members who have celiac disease are at
increased risk of developing the disease. Genetic susceptibility is related to specific HLA markers. More
than 97% of individuals with celiac disease in the United States have DQ2 and/or DQ8 HLA markers
compared to approximately 40% of the general population.(3) A definitive diagnosis of celiac disease
requires a jejunal biopsy demonstrating villous atrophy.(1-3) Given the invasive nature and cost of the
biopsy, serologic and genetic laboratory tests may be used to identify individuals with a high probability
of having celiac disease. Subsequently, those individuals with positive laboratory results should be
referred for small intestinal biopsy, thereby decreasing the number of unnecessary invasive procedures
(see Celiac Disease Comprehensive Cascade testing algorithm in Special Instructions). An individual
suspected of having celiac disease may be HLA typed to determine if the individual has the susceptibility
alleles DQ2 and/or DQ8.(4) In terms of serology, celiac disease is associated with a variety of
autoantibodies, including endomysial, tissue transglutaminase (tTG), and deamidated gliadin
antibodies.(4) Although the IgA isotype of these antibodies usually predominates in celiac disease,
individuals may also produce IgG isotypes, particularly if the individual is IgA deficient.(2) The most
sensitive and specific serologic tests are tTG and deamidated gliadin antibodies. The treatment for celiac
disease is maintenance of a gluten-free diet.(1-3) In most patients who adhere to this diet, levels of
associated autoantibodies decline and villous atrophy improves (see Celiac Disease Routine Treatment
Monitoring Algorithm in Special Instructions).This is typically accompanied by an improvement in
clinical symptoms. For your convenience, we recommend utilizing cascade testing for celiac disease.
Cascade testing ensures that testing proceeds in an algorithmic fashion. The following cascades are
available; select the appropriate 1 for your specific patient situation. Algorithms for the cascade tests are
available in Special Instructions. -CDCOM / Celiac Disease Comprehensive Cascade: complete testing
including HLA DQ typing and serology -CDSP / Celiac Disease Serology Cascade: complete serology
testing excluding HLA DQ -CDGF / Celiac Disease Gluten-Free Cascade: for patients already adhering to
a gluten-free diet. To order individual tests, see Celiac Disease Diagnostic Testing Algorithm in Special
Instructions. It should be noted that HLA typing is not required to establish a diagnosis of celiac disease.
Consider ordering CDSP / Celiac Disease Serology Cascade if HLA typing is not desired or has been
previously performed.
Useful For: Evaluating patients suspected of having celiac disease, including patients with compatible
symptoms, patients with atypical symptoms, and individuals at increased risk (family history, previous
diagnosis with associated disease) Comprehensive algorithmic evaluation including HLA typing
Interpretation: Immunoglobulin A (IgA): Total IgA levels below the age-specific reference range
suggest either a selective IgA deficiency or a more generalized immunodeficiency. For individuals with a
low IgA level, additional clinical and laboratory evaluation is recommended. Some individuals may have
a partial IgA deficiency in which the IgA levels are detectable but fall below the age-adjusted reference
range. For these individuals both IgA and IgG isotypes for tTG and deamidated gliadin antibodies are
recommended for the evaluation of celiac disease; IgA-tTG, IgG-tTG, IgA-deamidated gliadin, and
IgG-deamidated gliadin antibody assays are performed in this cascade. For individuals who have selective
IgA deficiency with undetectable levels of IgA, only IgG-tTG and IgG-deamidated gliadin antibody
assays are performed. HLA-DQ Typing: Approximately 90% to 95% of patients with celiac disease have
the HLA DQ2 allele; most of the remaining patients with celiac disease have the HLA DQ8 allele.
Individuals who do not carry either of these alleles are unlikely to have celiac disease. However,
individuals with these alleles may not, during their lifetime, develop celiac disease. Therefore, the
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 466
presence of DQ2 or DQ8 does not conclusively establish a diagnosis of celiac disease. Individuals with
DQ2 and/or DQ8 alleles, in the context of positive serology and compatible clinical symptoms, should be
referred for small intestinal biopsy. HLA typing may be especially helpful for those patients who have
begun to follow a gluten-free diet prior to a confirmed diagnosis of celiac disease.(4) Tissue
Transglutaminase (tTG) Antibody, IgA/IgG: Individuals positive for tTG antibodies of the IgA isotype
likely have celiac disease and small intestinal biopsy is recommended. For individuals with selective IgA
deficiency, testing for tTG antibodies of the IgG isotype is performed. In these individuals, a positive
IgG-tTG antibody result suggests a diagnosis of celiac disease. However, just as with the IgA-tTG
antibody, a biopsy should be performed to confirm the diagnosis. Negative tTG IgA and/or IgG antibody
serology does not exclude a diagnosis of celiac disease, as antibody levels decrease over time in patients
who have been following a gluten-free diet. Gliadin (Deamidated) Antibody, IgA/IgG: Positivity for
deamidated gliadin antibodies of the IgA isotype is suggestive of celiac disease, and small intestinal
biopsy is recommended. For individuals with selective IgA deficiency, testing for deamidated gliadin
antibodies of the IgG isotype is performed. In these individuals, a positive IgG-deamidated gliadin
antibody result suggests a diagnosis of celiac disease. However, just as with the IgA-deamidated gliadin
antibody, a biopsy should be performed to confirm the diagnosis. Negative deamidated gliadin IgA and/or
IgG antibody serology does not exclude a diagnosis of celiac disease, as antibody levels decrease over
time in patients who have been following a gluten-free diet. Endomysial (EMA) Antibody, IgA: Positivity
for EMA antibodies of the IgA isotype is suggestive of celiac disease, and small intestinal biopsy is
recommended. For individuals with selective IgA deficiency, evaluation of EMA antibodies is not
indicated. Negative EMA antibody serology does not exclude a diagnosis of celiac disease, as antibody
levels decrease over time in patients who have been following a gluten-free diet.
Reference Values:
IMMUNOGLOBULIN A (IgA)
0-<5 months: 7-37 mg/dL
5-<9 months: 16-50 mg/dL
9-<15 months: 27-66 mg/dL
15-<24 months: 36-79 mg/dL
2-<4 years: 27-246 mg/dL
4-<7 years: 29-256 mg/dL
7-<10 years: 34-274 mg/dL
10-<13 years: 42-295 mg/dL
13-<16 years: 52-319 mg/dL
16-<18 years: 60-337 mg/dL
> or =18 years: 61-356 mg/dL
HLA-DQ TYPING
Presence of DQ2 or DQ8 alleles associated with celiac disease
Clinical References: 1. Green PH, Cellier C: Medical progress: Celiac disease. N Engl J Med
2007;357:1731-1743 2. Green PH, Jabri B: Celiac disease. Ann Rev Med 2006;57:207-221 3. Harrison
MS, Wehbi M, Obideen K: Celiac disease: More common than you think. Cleve Clin J Med
2007;74:209-215 4. Update on celiac disease: New standards and new tests. Mayo Communique (2008)
Interpretation: HLA-DQ Typing: Approximately 90% to 95% of patients with celiac disease have
the HLA-DQ2 allele; most of the remaining patients with celiac disease have the HLA-DQ8 allele.
Individuals who do not carry either of these alleles are unlikely to have celiac disease. For these
individuals, no further serologic testing is required. However, individuals with these alleles may not,
during their lifetime, develop celiac disease. Therefore, the presence of DQ2 or DQ8 does not
conclusively establish a diagnosis of celiac disease. For individuals with DQ2 and/or DQ8 alleles, in the
context of positive serology and compatible clinical symptoms, small intestinal biopsy is recommended.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 467
Immunoglobulin A (IgA): Total IgA levels below the age-specific reference range suggest either a
selective IgA deficiency or a more generalized immunodeficiency. For individuals with a low IgA level,
additional clinical and laboratory evaluation is recommended. Some individuals may have a partial IgA
deficiency in which the IgA levels are detectable, but fall below the age-adjusted reference range. For
these individuals, both IgA and IgG isotypes for tTG and deamidated gliadin antibodies are
recommended for the evaluation of celiac disease. Tissue Transglutaminase (tTG) Antibody, IgA/IgG:
Individuals positive for tTG antibodies of the IgA and/or IgG isotype may have celiac disease and small
intestinal biopsy is recommended. Negative tTG IgA and/or IgG antibody serology does not exclude a
diagnosis of celiac disease, as antibody levels decrease over time in patients who have been following a
gluten-free diet. Gliadin (Deamidated) Antibody, IgA/IgG: Positivity for deamidated gliadin antibodies
of the IgA and/or IgG isotype is suggestive of celiac disease, and small intestinal biopsy is
recommended. Negative deamidated gliadin IgA and/or IgG antibody serology does not exclude a
diagnosis of celiac disease, as antibody levels decrease over time in patients who have been following a
gluten-free diet.
Clinical References: 1. Green PHR, Cellier C: Medical progress: Celiac disease. N EngL J Med
2007;357:1731-1743 2. Green PHR, Jabri J: Celiac disease. Ann Rev Med 2006;57;207-221 3. Harrison
MS, Wehbi M, Obideen K: Celiac disease: More common than you think. Cleve Clinic J Med
2007;74:209-215 4. Update on celiac disease: New standards and new tests. Mayo Communique (2008)
Interpretation: Immunoglobulin A (IgA): Total IgA levels below the age-specific reference range
suggest either a selective IgA deficiency or a more generalized immunodeficiency. For individuals with
a low IgA level, additional clinical and laboratory evaluation is recommended. Some individuals may
have a partial IgA deficiency in which the IgA levels are detectable but fall below the age-adjusted
reference range. For these individuals, both IgA and IgG isotypes for tTG and deamidated gliadin
antibodies are recommended for the evaluation of celiac disease; IgA-tTG, IgG-tTG, IgA-deamidated
gliadin, and IgG-deamidated gliadin antibody assays are performed in this cascade. For individuals who
have selective IgA deficiency or undetectable levels of IgA, only IgG-tTG and IgG-deamidated gliadin
antibody assays are performed. Tissue Transglutaminase (tTG) Ab, IgA/IgG: Individuals positive for
tTG antibodies of the IgA isotype likely have celiac disease and a small intestinal biopsy is
recommended. For individuals with selective IgA deficiency, testing for tTG antibodies of the IgG
isotype is performed. In these individuals, a positive IgG-tTG antibody result suggests a diagnosis of
celiac disease. However, just as with the IgA-tTG antibody, a biopsy should be performed to confirm
the diagnosis. Negative tTG IgA and/or IgG antibody serology does not exclude a diagnosis of celiac
disease, as antibody levels decrease over time in patients who have been following a gluten-free diet.
Gliadin (Deamidated) Ab, IgA/IgG: Positivity for deamidated gliadin antibodies of the IgA isotype is
suggestive of celiac disease; small intestinal biopsy is recommended. For individuals with selective IgA
deficiency, testing for deamidated gliadin antibodies of the IgG isotype is performed. In these
individuals, a positive IgG-deamidated gliadin antibody result suggests a diagnosis of celiac disease.
However, just as with the IgA-deamidated gliadin antibody, a biopsy should be performed to confirm
the diagnosis. Negative deamidated gliadin IgA and/or IgG antibody serology does not exclude a
diagnosis of celiac disease, as antibody levels decrease over time in patients who have been following a
gluten-free diet. Endomysial (EMA) Ab, IgA: Positivity for EMA antibodies of the IgA isotype is
suggestive of celiac disease, and small intestinal biopsy is recommended. For individuals with selective
IgA deficiency, evaluation of EMA antibodies is not indicated. Negative EMA antibody serology does
not exclude a diagnosis of celiac disease as antibody levels decrease over time in patients who have
been following a gluten-free diet.
Reference Values:
Immunoglobulin A
0-<5 months: 7-37 mg/dL
5-<9 months: 16-50 mg/dL
9-<15 months: 27-66 mg/dL
15-<24 months: 36-79 mg/dL
2-<4 years: 27-246 mg/dL
4-<7 years: 29-256 mg/dL
7-<10 years: 34-274 mg/dL
10-<13 years: 42-295 mg/dL
13-<16 years: 52-319 mg/dL
16-<18 years: 60-337 mg/dL
> or =18 years: 61-356 mg/dL
Clinical References: 1. Green PHR, Cellier C: Medical progress: Celiac disease. N Engl J Med
2007;357:1731-1743 2. Green PHR, Jabri J: Celiac disease. Ann Rev Med 2006;57;207-221 3. Harrison
MS, Wehbi M, Obideen K: Celiac disease: More common than you think. Cleve Clinic J Med
2007;74:209-215 4. Update on celiac disease: New standards and new tests. Mayo Communique (2008)
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 469
Useful For: An aid in the diagnosis of joint disease, systemic disease, inflammation, malignancy,
infection, and trauma
Interpretation: Trauma and hemorrhage may result in increased red and white cells; red cells
predominate. White blood cells are increased in inflammatory and infectious processes: -Neutrophils
predominate in bacterial infections -Lymphocytes predominate in viral infections -Macrophages may be
increased in inflammatory and infectious processes -Eosinophils may be increased in parasitic or fungal
infections
Reference Values:
TOTAL NUCLEATED CELLS:
Synovial fluid: <150/mcL
Peritoneal/pleural/pericardial fluid: <500/mcL
NEUTROPHILS:
Synovial Fluid: <25%
Peritoneal/pleural/pericardial fluid: <25%
LYMPHOCYTES:
Synovial fluid: <75%
MONOCYTES/MACROPHAGES:
Synovial fluid: 70%
Useful For: Diagnosis of idiopathic (autoimmune) thrombocytopenia purpura (ITP) and diagnosis of
immune thrombocytopenia associated with systemic lupus erythematosus or other disorders associated
with autoimmune phenomena
Interpretation: A test result showing optical density (OD) values equal to or greater than the cutoff of
the negative controls (run specific) corresponding to the glycoprotein is regarded as positive results. The
patient report will include an overall interpretation and a negative/positive result for each glycoprotein
(GPIIB/IIIa, GPIb/IX, and GPIa/IIa). Additionally, the patients observed OD value and the negative
control cutoff value for the patient-specific assay run will be included on the report. A positive test in the
presence of thrombocytopenia (not explained by other findings) is suggestive of idiopathic (autoimmune)
thrombocytopenic purpura. Similarly, a positive test in a thrombocytopenic patient with systemic lupus
erythematosus is consistent with an autoimmune cause. Patients who are septic may also have a positive
test with reactivity against most glycoproteins. Presence of reactivity to some glycoproteins has no clearly
established clinical significance. Borderline positive results need to be interpreted in the right clinical
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 470
context.
Reference Values:
Not applicable
Clinical References: 1. Lochowicz AJ, Curtis BR: Clinical applications of platelet antibody and
antigen testing. Lab Medi 2011;42:687-692 2. Davoren A, Bussel J, Curtis BR, et al: Prospective
evaluation of a new platelet glycoprotein (GP)-specific assay (PakAuto) in the diagnosis of autoimmune
thrombocytopenia (AITP). Am J Hematol 2005 Mar;78(3):193-197 3. Moore SB, DeGoey SR: Serum
platelet antibody testing: evaluation of solid-phase enzyme immunoassay and comparison with indirect
immunofluorescence. Am J Clin Pathol 1998;109:190-195
Useful For: An alternative to invasive tissue biopsies for the determination of BRAF V600E and
V600 K mutations Identification of patients with melanoma who are most likely to benefit from targeted
therapies
Useful For: Noninvasive screening for aneuploidies of chromosomes 13, 18, 21, and sex
chromosomes X and Y in pregnancies
Interpretation: Normal representation of material from chromosomes 13, 18, 21, X, and Y will be
reported as normal, indicating a low risk for trisomy 13, trisomy 18, trisomy 21, and sex chromosome
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 471
aneuploidies in the fetus. Fetal sex will be reported. If Y chromosome material is detected, this is
suggestive of a male fetus. If Y chromosome material is not detected, this is suggestive of a female
fetus. Increased amounts of chromosomal material will be reported as positive for having a trisomy of
the identified chromosome for chromosomes 13, 18, or 21. This screen will also report abnormal
amounts of chromosomal material of sex chromosomes X and Y, including monosomy X, XXX, XXY,
and XYY. While most specimens undergoing this analysis can be readily characterized, on rare
occasions equivocal or incidental results such as aneuploidy of chromosomes other than 13, 18, 21, X,
Y, as well as other genomic unbalanced rearrangements, may not allow for standard interpretation of
this aneuploidy screen. In these situations, a new maternal blood specimen may be requested or a
recommendation for other screening measures or diagnostic cytogenetic testing will be made.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Gil MM, Quezada MS, Revello R, et al: Analysis of cell-free DNA in
maternal blood in screening for fetal aneuploidies: updated meta-analysis. Ultrasound Obstet Gynecol
2015;45:249-266 2. ACOG/SMFM Joint Committee Opinion: Noninvasive prenatal testing for fetal
aneuploidy. No. 640, Dec 2015 3. Bianchi DW, Parker RL, Wentworth J, et al: DNA sequencing versus
standard prenatal aneuploidy screening. N Engl J Med 2014 Feb;370:799-808 4. Devers PL, Cronister A,
Ormond KE, et al: Noninvasive prenatal testing/noninvasive prenatal diagnosis: the position of the
National Society of Genetic Counselors. J Genet Counsel 2013;22:291-295 5. Gregg AR, Skotko BG,
Benkendorf JL, et al: Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position
statement of the American College of Medical Genetics and Genomics. Genet Med 2016 6. Jensen TJ,
Zwiefelhofer T, Tim RC, et al: High-throughput massively parallel sequencing for fetal aneuploidy
detection from maternal plasma. PLOS ONE 2012 Mar;8:1-8 7. Huang X, Zheng J, Chen M, et al:
Noninvasive prenatal testing of trisomies 21 and 18 by massively parallel sequencing of maternal plasma
DNA in twin pregnancies. Prenatal Diagnosis 2014;34:335-340
Interpretation: This request will be processed as a consultation. Appropriate stains will be performed
and a diagnostic interpretation provided.
Reference Values:
This request will be processed as a consultation. Appropriate dissection will be performed and an
interpretive report provided.
Clinical References: 1. Collins KA, Powers JM: Chapter 20: Autopsy procedures for the Brain,
Spinal Cord, and Neuromuscular System. In Autopsy Performance and Reporting. Second Edition. Edited
by KA Collins, GM Hutchins GM. College of American Pathologists, 2003 2. Crain BJ, Mirra SS:
Chapter 21: The Autopsy in Cases of Alzheimers Disease and Other Dementias. In Autopsy
Performance and Reporting. Second Edition. Edited by KA Collins, GM Hutchins. College of American
Pathologists, 2003
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 472
calcinosis, Raynaud phenomenon, esophageal hypomotility, sclerodactyly, and telangiectasia.(1)
Centromere antibodies were originally detected by their distinctive pattern of fine-speckled nuclear
staining on cell substrates used in the fluorescent antinuclear antibody test.(2) In subsequent studies,
centromere antibodies were found to react with several centromere proteins of 18 kDa, 80 kDa, and 140
kDa named as CENP-A, CENP-B, and CENP-C, respectively.(3) Several putative epitopes associated
with these autoantigens have been described. The CENP-B antigen is believed to be the primary
autoantigen and is recognized by all sera that contain centromere antibodies.
Useful For: Evaluating patients with clinical signs and symptoms compatible with systemic sclerosis
including skin involvement, Raynaud phenomenon, and arthralgias As an aid in the diagnosis of
calcinosis, Raynaud phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasis (CREST)
syndrome
Interpretation: In various reported clinical studies, centromere antibodies occur in 50% to 96% of
patients with calcinosis, Raynaud phenomenon, esophageal dysfunction, sclerodactyly, and
telangiectasis (CREST) syndrome. A positive test for centromere antibodies is strongly associated with
CREST syndrome. The presence of detectable levels of centromere antibodies may antedate the
appearance of diagnostic clinical features of CREST syndrome by several years.
Reference Values:
<1.0 U (negative)
> or =1.0 U (positive)
Reference values apply to all ages.
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 473
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 474
typically occurs in the first decade of life. Individuals with I-cell disease typically show an increased
excretion of ceramide trihexosides and sulfatides in urine.
Useful For: Identifying patients with Fabry disease Identifying patients with metachromatic
leukodystrophy Identifying patients with saposin B deficiency Identifying patients with multiple
sulfatase deficiency Identifying patients with mucolipidosis II (I-cell disease)
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Desnick RJ, Ioannou YA, Eng CM: Alpha-galactosidase A deficiency:
Fabry disease. Edited by D Valle, AL Beaudet, B Vogelstein, et al. New York, McGraw-Hill Book
Company. Accessed 3/16/2016. Available at
http://ommbid.mhmedical.com/content.aspx?bookid=971&Sectionid=62644837 2. Kuchar L,
Ledvinova J, Hrebicek M, et al: Prosaposin deficiency and saposin B deficiency (activator-deficient
metachromatic leukodystrophy): report on two patients detected by analysis of urinary sphingolipids
and carrying novel PSAP gene mutations. Am J Med Genet A 2009 Feb 15;149A(4):613-621 3. Mehta
A, Hughes DA: Fabry disease. In GeneReviews Edited by RA Pagon, MP Adam, HH Ardinger, et al.
University of Washington, Seattle; 1993-2016. Updated 2013 Oct 17. Available at
http://www.ncbi.nlm.nih.gov/books/NBK1292/ 4. Schlotawa L, Ennemann EC, Radhakrishnan K, et al:
SUMF1 mutations affecting stability and activity of formylglycine generating enzyme predict clinical
outcome in multiple sulfatase deficiency. Eur J Hum Genet 2011;19:253-261 5. Gieselmann V,
Ingeborg K: Metachromatic leukodystrophy. Edited by D Valle, AL Beaudet, B Vogelstein, et al. New
York, McGraw-Hill Book Company. Accessed 3/16/2016. Available at
http://ommbid.mhmedical.com/content.aspx?bookid=971&Sectionid=62644361 6. Leroy JG, Cathey S,
Friez MJ: Mucolipidosis II. In GeneReviews Edited by RA Pagon, MP Adam, HH Ardinger, et al.
University of Washington, Seattle; 1993-2016. Updated 2012 May 10. Available at
http://www.ncbi.nlm.nih.gov/books/NBK1828/
Useful For: Identifying patients with Fabry disease Identifying patients with metachromatic
leukodystrophy Identifying patients with saposin B deficiency Identifying patients with multiple
sulfatase deficiency Identifying patients with mucolipidosis II (I-cell disease)
Reference Values:
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 475
Only orderable as part of a profile. See LYSDU / Lysosomal Storage Disorders Screen, Urine.
For more information regarding ceramide trihexosides and sulfatides, see CTSA / Ceramide
Trihexosides and Sulfatides, Urine.
Useful For: Evaluation for risk of major adverse events due to cardiovascular disease within the next 1
to 5 years
Interpretation: Elevated plasma ceramides are associated with increased risk of myocardial infarction,
acute coronary syndromes, and mortality within 1 to 5 years. Ceramide Score Relative Risk Risk
Category 0-2 1.0 Lower 3-6 1.8 Moderate 7-9 2.3 Increased 10-12 5.1 Higher Score is based on trial data
including >4,000 subjects.
Reference Values:
Ceramide (16:0): 0.19-0.36 mcmol/L
Ceramide (18:0): 0.05-0.14 mcmol/L
Ceramide (24:1): 0.65-1.65 mcmol/L
Ceramide (16:0)/(24:0): <0.11
Ceramide (18:0)/(24:0): <0.05
Ceramide (24:1)/(24:0): <0.45
Ceramide Risk Score:
0-2 Lower risk
3-6 Moderate risk
7-9 Increased risk
10-12 Higher risk
Reference values have not been established for patients who are <18 years of age.
Note: Ceramide (24:0) alone has not been independently associated with disease and will not be
reported.
Clinical References: 1. Cheng JM, Suoniemi M, Kardys I, et al: Plasma concentrations of molecular
lipid species in relation to coronary plaque characteristics and cardiovascular outcome: Results of the
ATHEROREMO-IVUS study. Atherosclerosis 2015;243:560-566 2. Pan W, Yu J, Shi R, et al: Elevation
of ceramide and activation of secretory acid sphingomyelinase in patients with acute coronary syndromes.
Coron Artery Dis 2014;25:230-235 3. Tarasov K, Ekroos K, Suoniemi M, et al: Molecular lipids identify
cardiovascular risk and are efficiently lowered by simvastatin and PCSK9 deficiency. J Clin Endocrinol
Metab 2014;99:E45-52 4. Spijkers LJ, van den Akker RF, Janssen BJ, et al: Hypertension is associated
with marked alterations in sphingolipid biology: a potential role for ceramide. PLoS One 2011;6:e21817
5. Yu RK, Tsai YT, Ariga T, Yanagisawa M: Structures, biosynthesis, and functions of gangliosides--an
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 476
overview. J Oleo Sci 2011;60:537-544 6. Bergman BC, Brozinick JT, Strauss A, et al: Serum
sphingolipids: relationships to insulin sensitivity and changes with exercise in humans. Am J Physiol
Endocrinol Metab 2015;309:E398-408 7. Ng TW, Ooi EM, Watts GF, et al: Dose-dependent effects of
rosuvastatin on the plasma sphingolipidome and phospholipidome in the metabolic syndrome. J Clin
Endocrinol Metab 2014;99:E2335-2340 8. Laaksonen R, Ekroos K, Sysi-Aho M, et al: Plasma ceramides
predict cardiovascular death in patients with stable coronary artery disease and acute coronary syndromes
beyond LDL-cholesterol. Eur Heart J [epub ahead of print] April 28th, 2016.
DOI:10.1093/eurheartj/ehw148
Reference Values:
CSF index: 0.00-0.85
CSF IgG: 0.0-8.1 mg/dL
CSF albumin: 0.0-27.0 mg/dL
Serum IgG
0-4 months: 100-334 mg/dL
5-8 months: 164-588 mg/dL
9-14 months: 246-904 mg/dL
15-23 months: 313-1,170 mg/dL
2-3 years: 295-1,156 mg/dL
4-6 years: 386-1,470 mg/dL
7-9 years: 462-1,682 mg/dL
10-12 years: 503-1,719 mg/dL
13-15 years: 509-1,580 mg/dL
16-17 years: 487-1,327 mg/dL
> or =18 years: 767-1,590 mg/dL
Serum albumin: 3,200-4,800 mg/dL
CSF IgG/albumin: 0.00-0.21
Serum IgG/albumin: 0.0-0.4
CSF IgG synthesis rate: 0-12 mg/24 hours
Clinical References: 1. Tourtellotte WW, Walsh MJ, Baumhefner RW, et al: The current status of
multiple sclerosis intra-blood-brain-barrier IgG synthesis. Ann NY Acad Sci 1984;436:52-67 2.
Bloomer LC, Bray PF: Relative value of three laboratory methods in the diagnosis of multiple sclerosis.
Clin Chem 1981;27:2011-2013 3. Hische EA, van der Helm HJ: Rate of synthesis of IgG within the
blood-brain barrier and the IgG index compared in the diagnosis of multiple sclerosis. Clin Chem
1987;33:113-114 4. Swanson JW: Multiple Sclerosis: update in diagnosis and review of prognostic
factors. Mayo Clin Proc 1989;64:577-586 5. Markowitz H, Kokmen E: Neurologic diseases and the
cerebrospinal fluid immunoglobulin profile. Mayo Clin Proc 1983;58:273-274
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 477
FCERT Certolizumab pegol and Anti-Certolizumab Antibodies, Serum
75198 Clinical Information:
Interpretation: Certolizumab (CTZ) Endoscopic response and remission are associated with higher
plasma concentrations of certolizumab (CTZ).1 A significant inverse relationship has been found between
plasma concentration of CTZ and C-reactive protein.1 In a study of CTZ dose optimization in patients
with CD, remission rates were higher in patients whose CTZ levels were greater than 27.5 ug/mL.2
Antibodies to Certolizumab Clinical trials exploring CTZ immunogenicity have not found a relationship
between development of antibodies to certolizumab (ATC) and clinical response. 3, 4, 5, 6, 7 Some
patients on anti-TNF therapy may develop antibodies that resolve over time. 8, 9, 10 The presence of
antibodies to certolizumab has been associated with decreased serum CTZ levels and decreased clinical
efficacy in rheumatoid arthritis trials.11 In patients with CD that fail to respond to anti TNF therapy but
have a therapeutic drug concentration and low or undetectable antibody levels, clinical guidelines suggest
a switch to another drug class.12 In patients with Irritable Bowel Disease (IBD) with good response to
other biologic therapies, supra therapeutic doses have been reduced without disease flares, resulting in
significant cost savings.13
Reference Values:
Clinically Reportable Ranges:
Certolizumab 3-84 ug/mL
Anti-Certolizumab antibody 5 - 160 AU/mL
FCERE Ceruloplasmin
75205 Clinical Information: Decreased levels of ceruloplasmin are found in Wilson's Disease, fulminant
liver failure, intestinal malabsorption, renal failure resulting in proteinuria, chronic active hepatitis and
malnutrition. Elevated levels are found in primary biliary cirrhosis, pregnancy (first trimester), oral
contraceptive use and in acute inflammatory conditions since ceruloplasmin is an acute phase reactant.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 478
Reference Values:
Age Male (mg/dL) Female (mg/dL)
0 30 Days 8 25 3 28
31 Days 11 Months 15 48 15 43
1 3 Years 25 56 29 54
4 6 Years 29 56 26 54
7 9 Years 25 52 23 - 48
10 12 Years 21 51 21 48
13 15 Years 20 50 21 - 46
16 18 Years 20 - 45 22 - 50
Adult 18 36 18 - 53
Clinical References: The pediatric ranges are derived from the following criteria: Soldin SJ, Hicks
JM, Bailey J et al Pediatric reference ranges for Beta-2 Microglobulin and ceruloplasmin. Clin Chem
1997; 43:S1999 Pediatric Reference Ranges, 2nd., SF Soldin, et al. editors. AACC Press, Washington,
DC 1997.
Useful For: Screening for cervical carcinoma and a number of infections of the female genital tract
including human papillomavirus, herpes, Candida, and Trichomonas
Clinical References: 1. Wright TC Jr, Cox JT, Massad LS, et al: ASCCP-Sponsored Consensus
Conference. 2001 Consensus Guidelines for the management of women with cervical cytological
abnormalities. JAMA 2002 April;287(16):2120-2129 2. Solomon D, Davey D, Kurman R, et al: The
2001 Bethesda System: terminology for reporting results of cervical cytology-Consensus Statement
JAMA. 2002 April;287(16):2114-2119
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 479
to sexual activity and possibly sexually transmitted viral infections such as human papilloma virus.
Most cervical carcinomas and precancerous conditions occur in the transformation zone
(squamo-columnar junction), therefore, this area needs to be sampled if optimum results are to be
obtained.
Useful For: Screening for cervical carcinoma and a number of infections of the female genital tract
including human papillomavirus, herpes, Candida, and Trichomonas
Clinical References: 1. Wright TC Jr, Cox JT, Massad LS, et al: ASCCP-Sponsored Consensus
Conference. 2001 Consensus Guidelines for the management of women with cervical cytological
abnormalities. JAMA 2002 April;287(16):2120-2129 2. Solomon D, Davey D, Kurman R, et al: The 2001
Bethesda System: terminology for reporting results of cervical cytology-Consensus Statement. JAMA
2002 April;287(16):2114-2119
Useful For: Follow-up testing to identify mutations in individuals with a clinical diagnosis of cystic
fibrosis (CF) and a negative targeted mutation analysis for the common mutations Identification of
mutations in individuals with atypical presentations of CF (eg, congenital bilateral absence of the vas
deferens or pancreatitis) Identification of mutations in individuals where detection rates by targeted
mutation analysis are low or unknown for their ethnic background Identification of patients who may
respond to cystic fibrosis transmembrane conductance regulator (CFTR) potentiator therapy This is not
the preferred genetic test for carrier screening or initial diagnosis. For these situations, order CFB / Cystic
Fibrosis Mutation Analysis, 106-Mutation Panel
Interpretation: All detected alterations are evaluated according to American College of Medical
Genetics recommendations.(1) Variants are classified based on known, predicted, or possible
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 480
pathogenicity and reported with interpretive comments detailing their potential or known significance.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for
standards of interpretation and reporting of sequence variations: revisions 2007. Genet Med
2008;10(4):294-300 2. Rosenstein BJ, Zeitlin PL: Cystic fibrosis. Lancet 1998 Jan
24;351(9098):277-282 3. Strom CM, Huang D, Chen C, et al: Extensive sequencing of the cystic
fibrosis transmembrane regulator gene: assay validation and unexpected benefits of developing a
comprehensive test. Genet Med 2003 Jan-Feb;5(1):9-14 4. De Boeck K, Munck A, Walker S, et al:
Efficacy and safety of ivacaftor in patients with Cystic Fibrosis and the G551D gating mutation. J Cyst
Fibros 2014 Dec;13(6):674-680 doi: 10.1016/j.jcf.2014.09.005
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 481
FAMCE Cheese American IgE
57914 Interpretation: Class IgE (kU/L) Comment 0 <0.35 Below Detection 1 0.35 0.69 Low Positive 2
0.70 3.49 Moderate Positive 3 3.50 17.49 Positive 4 17.50 49.99 Strong Positive 5 50.00
99.99 Very Strong Positive 6 >99.99 Very Strong Positive
Reference Values:
<0.35 kU/L
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical utility
of food-specific IgG tests has not been established. These tests can be used in special clinical situations to
select foods for evaluation by diet elimination and challenge in patients who have food-related
complaints. It should be recognized that the presence of food-specific IgG alone cannot be taken as
evidence of food allergy and only indicates immunologic sensitization by the food allergen in question.
This test should only be ordered by physicians who recognize the limitations of the test.
Reference Values:
<0.35 kU/L
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 482
responsible for eliciting signs and symptoms. The level of IgE antibodies in serum varies directly with the
concentration of IgE antibodies expressed as a class score or kU/L.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.70 Equivocal
2 0.71-3.5 Positive
3 3.51-17.5 Positive
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 483
5 50.1-100.0 Strongly positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Evaluation for hereditary susceptibility to breast cancer or Li-Fraumeni-like syndrome
Identification of a familial CHEK2 mutation to allow for predictive testing in family members
Interpretation: All detected alterations are evaluated according to American College of Medical
Genetics recommendations.(3) Variants are classified based on known, predicted, or possible
pathogenicity and reported with interpretive comments detailing their potential or known significance.
Reference Values:
An interpretive report will be provided.
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 485
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 486
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: Providing genetic information for patients with hypereosinophilic syndrome (HES) and
systemic mast cell disease (SMCD) involving CHIC2 deletion Identifying and tracking chromosome
abnormalities and response to therapy
Interpretation: A neoplastic clone is detected when the percent of cells with an abnormality exceeds
the normal reference range. Detection of an abnormal clone is usually associated with hypereosinophilic
syndrome or systemic mastocytosis associated with eosinophilia. The absence of an abnormal clone
does not rule out the presence of neoplastic disorder.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Pardanani A, Ketterling RP, Brockman SR, et al: CHIC2 deletion, a
surrogate for FIP1L1-PDGFRA fusion, occurs in systemic mastocytosis associated with eosinophilia
and predicts response to imatinib mesylate therapy. Blood Nov 1 2003;102(9):3093-3096 2. Pardanani
A, Brockman SR, Paternoster SF, et al: F1P1L1-PDGFRA fusion: prevalence and clinicopathologic
correlates in 89 consecutive patients with moderate to severe eosiniphilia. Blood 2004;104:3038-3045 3.
Cools J, DeAngelo DJ, Gotlib J, et al: A tyrosine kinase created by fusion of the PDGFRA and FIP1L1
genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med Mar
2003;348(13):1201-1214
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE KU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 488
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 489
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical utility
of food-specific IgG tests has not been established. These tests can be used in special clinical situations to
select foods for evaluation by diet elimination and challenge in patients who have food-related
complaints. It should be recognized that the presence of food-specific IgG alone cannot be taken as
evidence of food allergy and only indicates immunologic sensitization by the food allergen in question.
This test should only be ordered by physicians who recognize the limitations of the test.
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 490
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 491
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: Aiding in the diagnosis of recent infection with Chikungunya virus in patients with recent
travel to endemic areas and a compatible clinical syndrome
Interpretation: IgM and IgG Negative: -No serologic evidence of exposure to Chikungunya virus.
Repeat testing on a new specimen collected in 5 to 10 days is recommended if clinical suspicion persists.
IgM and IgG Positive: -IgM and IgG antibodies to Chikungunya virus detected, suggesting recent or past
infection. IgM antibodies to Chikungunya virus may remain detectable for 3 to 4 months postinfection.
IgM Positive, IgG Negative: -IgM antibodies to Chikungunya virus detected, suggesting recent infection.
Repeat testing in 5 to 10 days is recommended to demonstrate anti-Chikungunya virus IgG
seroconversion to confirm current infection. IgM Negative, IgG Positive: -IgG antibodies to Chikungunya
virus detected, suggesting past infection. IgM and/or IgG Borderline: -Repeat testing in 10 to 14 days is
recommended.
Reference Values:
IgM: Negative
IgG: Negative
Reference values apply to all ages.
Clinical References: Pan American Health Organization. Preparedness and Response for
Chikungunya virus. Introduction into the Americas. Washington, DC, PAHO 2011
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 492
CHIKI Chikungunya Interpretation
37102 Reference Values:
Only orderable as part of a profile. For more information see CHIKV / Chikungunya IgM and IgG,
Antibody, Serum.
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 493
CHIMU Chimerism Transplant No Cell Sort
62983 Clinical Information: Patients who have had donor hematopoietic cells infused for the purpose of
engraftment (ie, bone marrow transplant recipients) may have their blood or bone marrow monitored for
an estimate of the percentage of donor and recipient cells present. This can be done by first identifying
unique features of the donor's and the recipient's DNA prior to transplantation and then examining the
recipient's blood or bone marrow after the transplantation procedure has occurred. The presence of both
donor and recipient cells (chimerism) and the percentage of donor cells are indicators of transplant
success. Short tandem repeat (STR) sequences are used as identity markers. STRs are di-, tri-, or
tetra-nucleotide repeat sequences interspersed throughout the genome at specific sites. There is variability
in STR length among people and the STR lengths remain stable throughout life, making them useful as
identity markers. PCR is used to amplify selected STR regions from germline DNA of both donor and
recipient. The lengths of the amplified fragment are evaluated for differences (informative markers).
Following allogeneic hematopoietic cell infusion, the recipient blood or bone marrow can again be
evaluated for the informative STR regions to identify chimerism and estimate the proportions of donor
and recipient cells in the specimen.
Useful For: Determining the relative amounts of donor and recipient cells in a specimen An indicator
of bone marrow transplant success
Reference Values:
An interpretive report will be provided.
Clinical References: Antin JH, Childs R, Filipovich AH, et al: Establishment of complete and mixed
donor chimerism after allogenic lymphohematopoietic transplantation: recommendations from a
workshop at the 2001 Tandem Meetings. Biol Blood Marrow Transplant 2001;7:473-485
Useful For: Determining the relative amounts of donor and recipient cells in a specimen An indicator
of bone marrow transplant success
Clinical References: Antin JH, Childs R, Filipovich AH, et al: Establishment of complete and
mixed donor chimerism after allogenic lymphohematopoietic transplantation: recommendations from a
workshop at the 2001 Tandem Meetings. Biol Blood Marrow Transplant 2001;7:473-485
CHIDB Chimerism-Donor
83182 Clinical Information: Patients who have had donor hematopoietic cells infused for the purpose of
engraftment (ie, bone marrow transplant recipients) may have their blood or bone marrow monitored for
an estimate of the percentage of donor and recipient cells present. This can be done by first identifying
unique features of the donor's and the recipient's DNA prior to transplantation and then examining the
recipient's blood or bone marrow after the transplantation procedure has occurred. The presence of both
donor and recipient cells (chimerism) and the percentage of donor cells are indicators of transplant
success. Short tandem repeat (STR) sequences are used as identity markers. STRs are di-, tri-, or
tetra-nucleotide repeat sequences interspersed throughout the genome at specific sites. There is
variability in STR length among people and the STR lengths remain stable throughout life, making them
useful as identity markers. PCR is used to amplify selected STR regions from germline DNA of both
donor and recipient. The lengths of the amplified fragment are evaluated for differences (informative
markers). Following allogeneic hematopoietic cell infusion, the recipient blood or bone marrow can
again be evaluated for the informative STR regions to identify chimerism and estimate the proportions
of donor and recipient cells in the specimen.
Useful For: Determining the relative amounts of donor and recipient cells in a specimen An indicator
of bone marrow transplant success
Reference Values:
An interpretive report will be provided.
Clinical References: Antin JH, Childs R, Filipovich AH, et al: Establishment of complete and
mixed donor chimerism after allogenic lymphohematopoietic transplantation: recommendations from a
workshop at the 2001 Tandem Meetings. Biol Blood Marrow Transplant 2001;7:473-485
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Useful For: Determining the relative amounts of donor and recipient cells in a specimen An indicator
of bone marrow transplant success
Reference Values:
An interpretive report will be provided.
Clinical References: Antin JH, Childs R, Filipovich AH, et al: Establishment of complete and mixed
donor chimerism after allogenic lymphohematopoietic transplantation: recommendations from a
workshop at the 2001 Tandem Meetings. Biol Blood Marrow Transplant 2001;7:473-485
This test employs PCR amplification and agarose gel electrophoresis detection of a Chlamydia
pneumoniae-specific conserved genetic target. A positive result should be coupled with clinical indicators
for diagnosis. A "Not detected" result for this assay does not exclude Chlamydia pneumoniae involvement
in a disease process.
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phagosome. After cell entry, the EB reorganizes into reticulate particles (forming inclusion bodies) and
binary fission begins. After 18 to 24 hours, reticulate particles condense to form EBs. These new EBs are
released, beginning another infection cycle. Chlamydophila psittaci is the causative agent of psittacosis, a
disease characterized by pneumonia, headache, altered mentation, and hepatosplenomegaly. Psittacosis is
acquired by airborne transmission from infected birds. Chlamydophila pneumoniae (formerly known as
TWAR and, more recently, as Chlamydia pneumoniae) causes pneumonia in humans. It is unique because
it is a primary pathogen of humans, is spread from human to human, and apparently has no animal or bird
host. Chlamydophila pneumoniae is responsible for approximately 10% of pneumonia cases. Chlamydia
trachomatis has been implicated in a wide variety of infections in humans. It is a common cause of
nongonococcal urethritis and cervicitis, and many systemic complications of chlamydial infections have
been described. In females, this organism is a cause of pelvic inflammatory disease, salpingitis, and
endometritis. In males, epididymitis and Reiter syndrome occur. Lymphogranuloma venereum is a
sexually transmitted infection caused by Chlamydia trachomatis. It presents with a transient primary
genital lesion followed by suppurative regional lymphadenopathy. Occasionally, severe proctitis or
proctocolitis may develop. Chlamydia trachomatis also causes ophthalmologic infections, such as
trachoma (rare in the United States), adult inclusion conjunctivitis and inclusion conjunctivitis in
neonates. These disorders have traditionally been diagnosed by cytologic detection or culture. However,
molecular detection methods (CTRNA / Chlamydia trachomatis by Nucleic Acid Amplification
[GEN-PROBE]) may now represent a more sensitive diagnostic approach. Fitz-Hugh-Curtis syndrome
(perihepatitis) has been associated with chlamydiae.
Reference Values:
Chlamydophila pneumoniae
IgG: <1:64
IgM: <1:10
Chlamydophila psittaci
IgG: <1:64
IgM: <1:10
Chlamydia trachomatis
IgG: <1:64
IgM: <1:10
Clinical References: 1. Movahed MR: Infection with Chlamydia pneumoniae and atherosclerosis:
a review. J South Carolina Med Assoc 1999;95:303-308 2. Smith T: Chlamydia. In Diagnostic
Procedures for Viral, Rickettsial and Chlamydial Infections. Sixth edition. Edited by N Schmidt, R
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 497
Emmons. Washington, DC, APHA, 1989, pp 1165-1198 3. Sheffield PA, Moore DE, Voigt LF, et al:
The association between Chlamydia trachomatis serology and pelvic damage in women with tubal
ectopic gestations. Fertil Steril 1993;60:970-975
Reference Values:
Chlamydia trachomatis
Negative
Neisseria gonorrhoeae
Negative
Clinical References: 1. Centers for Disease Control and Prevention. 2002. Reporting of
laboratory-confirmed chlamydial infection and gonorrhea by providers affiliated with three large
Managed Care Organizations-United States, 1995-1999. MMWR Morb Mortal Wkly Rep
2002;51:256-259 2. Centers for Disease Control and Prevention: Sexually Transmitted Diseases
Treatment Guidelines, 2010. MMWR Morb Mortal Wkly Rep 2010;59:RR12 3. Crotchfelt KA, Pare B,
Gaydos C, Quinn TC: Detection of Chlamydia trachomatis by the GEN-PROBE AMPLIFIED
Chlamydia trachomatis Assay (AMP CT) in urine specimens from men and women and endocervical
specimens from women. J Clin Microbiol 1998 Feb;36(2):391-394 4. Gaydos CA, Quinn TC, Willis D,
et al: Performance of the APTIMA Combo 2 assay for detection of Chlamydia trachomatis and
Neisseria gonorrhoeae in female urine and endocervical swab specimens. J Clin Microbiol 2003
Jan;41(1):304-309 5. Chernesky MA, Jang DE: APTIMA transcription-mediated amplification assays
for Chlamydia trachomatis and Neisseria gonorrhoeae. Expert Rev Mol Diagn 2006 Jul;6(4):519-525
Reference Values:
Negative
Clinical References: 1. Centers for Disease Control and Prevention. 2002. Reporting of
laboratory-confirmed chlamydial infection and gonorrhea by providers affiliated with three large
Managed Care Organizations-United States, 1995-1999. MMWR Morb Mortal Wkly Rep
2002;51:256-259 2. Centers for Disease Control and Prevention: Sexually Transmitted Diseases
Treatment Guidelines, 2010. MMWR Morb Mortal Wkly Rep 2010;59:RR12 3. Crotchfelt KA, Pare B,
Gaydos C, Quinn TC: Detection of Chlamydia trachomatis by the GEN-PROBE AMPLIFIED Chlamydia
trachomatis Assay (AMP CT) in urine specimens from men and women and endocervical specimens from
women. J Clin Microbiol 1998 Feb;36(2):391-394 4. Gaydos CA, Quinn TC, Willis D, et al: Performance
of the APTIMA Combo 2 assay for detection of Chlamydia trachomatis and Neisseria gonorrhoeae in
female urine and endocervical swab specimens. J Clin Microbiol 2003 Jan;41(1):304-309 5. Chernesky
MA, Jang DE: APTIMA transcription-mediated amplification assays for Chlamydia trachomatis and
Neisseria gonorrhoeae. Expert Rev Mol Diagn 2006 Jul;6(4):519-525
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partners. The CDC also recommends that all pregnant women be given a screening test for Chlamydia
infection.(2) Repeat testing for test-of-cure is not recommended after treatment with a standard treatment
regimen unless patient compliance is in question, reinfection is suspected, or the patient's symptoms
persist. Repeat testing of pregnant women, 3 weeks after completion of therapy, is also recommended to
ensure therapeutic cure.(2) Culture was previously considered to be the gold standard test for diagnosis of
C trachomatis infection.(2) However, organisms are labile in vitro, and precise specimen collection,
transportation, and processing conditions are required to maintain organism viability, which is necessary
for successful culturing. In comparison, nucleic acid amplification testing (NAAT) provides superior
sensitivity and specificity and is now the recommended method for diagnosis in most cases.(3-5)
Immunoassays and nonamplification DNA tests are also available for C trachomatis detection, but these
methods are significantly less sensitive and less specific than NAAT.(2) Improved screening rates and
increased sensitivity of NAAT testing have resulted in an increased number of accurately diagnosed
cases.(2) Early identification of infection enables sexual partners to seek testing and treatment as soon as
possible and reduces the risk of disease spread. Prompt treatment reduces the risk of infertility in women.
Reference Values:
Negative
Clinical References: 1. Centers for Disease Control and Prevention. 2014. Recommendations for
the laboratory-based detection of chlamydia trachomatis and neisseria gonorrhoeae, 2014. MMWR
Morb Mortal Wkly Rep 2014;63:1-18 2. Centers for Disease Control and Prevention: Sexually
Transmitted Diseases Treatment Guidelines, 2010. MMWR Morb Mortal Wkly Rep 2010;59:RR12 3.
Crotchfelt KA, Pare B, Gaydos C, Quinn TC: Detection of Chlamydia trachomatis by the GEN-PROBE
AMPLIFIED Chlamydia trachomatis Assay (AMP CT) in urine specimens from men and women and
endocervical specimens from women. J Clin Microbiol 1998 Feb;36(2):391-394 4. Gaydos CA, Quinn
TC, Willis D, et al: Performance of the APTIMA Combo 2 assay for detection of Chlamydia
trachomatis and Neisseria gonorrhoeae in female urine and endocervical swab specimens. J Clin
Microbiol 2003 Jan;41(1):304-309 5. Chernesky MA, Jang DE: APTIMA transcription-mediated
amplification assays for Chlamydia trachomatis and Neisseria gonorrhoeae. Expert Rev Mol Diagn
2006 Jul;6(4):519-525
Alpha-Chlordane
Synonym(s): Cis-Chlordane
Results reported in ppb
Gamma-Chlordane
Synonym(s): Trans-Chlordane
Results reported in ppb
Trans-Nonachlor
Synonym(s): Chlordane Component
Results reported in ppb
Heptaclorepoxide
Synonym(s): Chlordane Metabolite
Results reported in ppb
Oxychlordane
Synonym(s): Chlordane Metabolite
Results reported in ppb
Heptchlor
Synonym(s): Chlordane Component
Results reported in ppb
Useful For: Monitoring chlordiazepoxide therapy Assessing toxicity Because chlordiazepoxide has a
wide therapeutic index and dose-dependent toxicity, routine drug monitoring is not indicated in all
patients
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Interpretation: A therapeutic dose will yield a serum concentration of 1,000 to 3,000 ng/mL. Toxic
concentration: >5,000 ng/mL
Reference Values:
Therapeutic concentration:
Chlordiazepoxide: 400-3,000 ng/mL
Nordiazepam: 100-500 ng/mL
Clinical References: 1. Langman, LJ, Bechtel L, Holstege CP, Chapter 35: Clinical Toxicology,
In Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Edited by CA Burtis, ER
Ashwood, DE Bruns. WB Saunders Company, Philadelphia, PA, 2011, pp 1109-1188 2. Tietz Textbook
of Clinical Chemistry and Molecular Diagnostics, Edited by CA Burtis, ER Ashwood, DE Bruns, WB
Saunders Company, Philadelphia, PA, 2011, Table 60.2, pp 1109-1188 3. Hiemke C, Baumann P,
Bergemann N, et al: AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Psychiatry:
Update 2011. Pharmacopsychiatry 2011;44:195-235
Reference Values:
40-224 mmol/24 hours
Clinical References: 1. Tietz Textbook of Clinical Chemistry. Third edition. Edited by CA Burtis,
ER Ashwood. Philadelphia, WB Saunders Company, 1999 2. Toffaletti J: Electrolytes. In Professional
Practice in Clinical Chemistry: A Review. Edited by DR Dufour, N Rifai. Washington, AACC Press,
1993 3. Kamel KS, Ethier JH, Richardson RM, et al: Urine electrolytes and osmolality: when and how
to use them. Am J Nephrol 1990;10:89-102
Reference Values:
Interpret with other clinical data.
Clinical References: 1. Tietz Textbook of Clinical Chemistry. Third edition. Edited by CA Burtis,
ER Ashwood. Philadelphia, WB Saunders Co, 1999 2. Toffaletti J: Electrolytes. In Professional Practice
in Clinical Chemistry: A Review. Edited by DR Dufour, N Rifai. Washington, AACC Press, 1993 3.
Kamel KS, Ethier JH, Richardson RM, et al: Urine electrolytes and osmolality: when and how to use
them. Am J Nephrol 1990;10:89-102
CL Chloride, Serum
8460 Clinical Information: Chloride (Cl) is the major anion in the extracelullar water space; its
physiological significance is in maintaining proper body water distribution, osmotic pressure, and normal
anion-cation balance in the extracellular fluid compartment. Chloride is increased in dehydration, renal
tubular acidosis (hyperchloremia metabolic acidosis), acute renal failure, metabolic acidosis associated
with prolonged diarrhea and loss of sodium bicarbonate, diabetes insipidus, adrenocortical hyperfuction,
salicylate intoxication and with excessive infusion of isotonic saline or extremely high dietary intake of
salt. Hyperchloremia acidosis may be a sign of severe renal tubular pathology. Chloride is decreased in
overhydration, chronic respiratory acidosis, salt-losing nephritis, metabolic alkalosis, congestive heart
failure, Addisonian crisis, certain types of metabolic acidosis, persistent gastric secretion and prolonged
vomiting, aldosteronism, bromide intoxication, syndrome of inappropriate antidiuretic hormone secretion,
and conditions associated with expansion of extracellular fluid volume.
Reference Values:
1-17 years: 102-112 mmol/L
> or =18 years: 98-107 mmol/L
Reference values have not been established for patients who are <12 months of age.
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Useful For: This test is of limited clinical utility.
Interpretation: Cerebrospinal fluid chloride levels generally reflect systemic (blood) chloride levels.
Reference Values:
120-130 mmol/L
The reference range listed on the report is the lower limit of the quantitation for the assay. The clinical
utility of food-specific IgG test has not been established. These tests can be used in special clinical
situations to select foods for evaluation by diet elimination and challenge in patients who have
food-related complaints. It should be recognized that the presence of food-specific IgG alone cannot be
taken as evidence of food allergy and only indicates immunologic sensitization by the food allergen in
question. This test should only be ordered by physicians who recognize the limitations of the test.
Reference Values:
Up to 80 pg/mL
This test was developed and its performance characteristics determined by Inter Science Institute. It
has not been cleared or approved by the US Food and Drug Administration. The FDA has determined
that such clearance or approval is not necessary.
FCHO Cholestanol
91157 Reference Values:
0-8 weeks: 0.89 - 5.18 ug/mL (n=38)
>8 weeks: 0.86 - 3.71 ug/mL (n=68)
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CHLBF Cholesterol, BF
82945 Clinical Information: Pleural Fluid: Quantitation of cholesterol in body fluids is clinically important
and relevant in particular to the diagnosis of a cholesterol effusion. Cholesterol effusions (also known as
pseudochylothorax or chyliform effusion) are important to differentiate from chylothorax, as their
etiologies and therapeutic management strategies differ. Pseudochylous or chyliform effusions accumulate
gradually through the breakdown of cellular lipids in long-standing effusions such as rheumatoid pleuritis,
tuberculosis, or myxedema and by definition the effluent contains high concentrations of cholesterol. The
fluid may have a milky or opalescent appearance and be similar to that of a chylous effusion, which
contains high concentrations of triglycerides in the form of chylomicrons. An elevated cholesterol >250
mg/dL defines a cholesterol effusion in pleural fluid. Peritoneal Fluid: Ascites is the pathologic
accumulation of excess fluid in the peritoneal cavity. Cholesterol analysis in peritoneal fluid may be a
useful index to separate malignant ascites (>45-48 mg/dL) from cirrhotic ascites. Using a cutoff value of
48 mg/dL, the sensitivity, specificity, positive and negative predictive value, and overall diagnostic
accuracy for differentiating malignant from nonmalignant ascites were reported as 96.5%, 96.6%, 93.3%,
98.3%, and 96.6%, respectively.(1) Synovial Fluid: Normal synovial fluid contains extremely low
concentrations of lipids. Abnormalities in synovial fluid lipids may be attributed to cholesterol-rich
pseudochylous effusions which may be associated with chronic rheumatoid arthritis, lipid droplets due to
traumatic injury and rarely due to severe chylous effusions associated with systemic lupus erythematosus,
filariasis, pancreatitis, and trauma.(1) However, these diseases can usually be differentiated clinically and
by gross and microscopic examination; quantification of lipids in synovial fluid only provides supporting
information to the clinical picture.
Useful For: Distinguishing between chylous and nonchylous effusions Identifying iatrogenic effusions
Interpretation: Not applicable
Reference Values:
Not applicable
Clinical References: 1. McPherson RA, Matthew RP, Henry JB: Cerebrospinal, Synovial, and
Serous Body Fluids. In Henry's Clinical Diagnosis and Management by Laboratory Methods.
Philadelphia, Saunders Elsevier, 2007, pp 426-454 2. Valdes L, Pose A, Suarez J, et al: Cholesterol: a
useful parameter for distinguishing between pleural exudates and transudates. Chest 1991;99:1097-1102
3. Tietz Textbook of Clinical Chemistry. Third edition. Edited by CA Burtis, ER Ashwood, WB
Saunders, Philadelphia, 1999, pp 1130, 1767-1770 4. Ellefson RD, Elveback L, Weidman W: Plasma
lipoproteins of children and youths in Rochester, MN. DHEW Publication No. (NIH) 1978;78-1472
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Reference Values:
The National Lipid Association and the National Cholesterol Education Program (NCEP) have set the
following guidelines for lipids (total cholesterol, triglycerides, high-density lipoprotein [HDL]
cholesterol, low-density lipoprotein [LDL] cholesterol, and non-HDL cholesterol) in adults ages 18 and
up:
HDL CHOLESTEROL
Males
> or =40 mg/dL
Females
> or =50 mg/dL
The Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children
and Adolescents has set the following guidelines for lipids (total cholesterol, triglycerides, HDL
cholesterol, LDL cholesterol, and non-HDL cholesterol) in children ages 2-17:
HDL CHOLESTEROL
Low HDL: <40 mg/dL
Borderline low: 40-45 mg/dL
Acceptable: >45 mg/dL
Clinical References: 1. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Edited
by CA Burtis, ER Ashwood, DE Bruns. St. Louis, MO: Elsevier Saunders, 2012 2. Rifai N, Warnick
GR: Laboratory Measurement of Lipids, Lipoproteins, and Apolipoproteins. AACC Press, Washington
DC, 1994 3. Jacobson TA, Ito MK, Maki KC, et al: National Lipid Association recommendations for
patient-centered management of dyslipidemia: Part 1 - executive summary. J Clin Lipidol 2014
Sep-Oct;8(5):473-488 4. Expert panel on integrated guidelines for cardiovascular health and risk
reduction in children and adolescents: summary report. Pediatrics 2011 Dec;128 Suppl 5:S213-S256
Reference Values:
The National Lipid Association and the National Cholesterol Education Program (NCEP) have set the
following guidelines for lipids (total cholesterol, triglycerides, high-density lipoprotein [HDL]
cholesterol, low-density lipoprotein [LDL] cholesterol, and non-HDL cholesterol) in adults ages 18 and
up:
TOTAL CHOLESTEROL
Desirable: <200 mg/dL
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Borderline high: 200-239 mg/dL
High: > or =240 mg/dL
The Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children
and Adolescents has set the following guidelines for lipids (total cholesterol, triglycerides, HDL
cholesterol, LDL cholesterol, and non-HDL cholesterol) in children 2 to 17 years of age:
TOTAL CHOLESTEROL
Acceptable: <170 mg/dL
Borderline high: 170-199 mg/dL
High: > or =200 mg/dL
Clinical References: 1. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Edited by
CA Burtis, ER Ashwood. St. Louis, MO: Elsevier Saunders, 2012 2. National Institute of Health (NIH)
Publication: Second Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood
Cholesterol in Adults. NIH Publication 93-3096. 1993 Sep;93:3096 3. Jacobson TA, Ito MK, Maki KC, et
al: National Lipid Association recommendations for patient-centered management of dyslipidemia: Part
1-executive summary. J Clin Lipidol 2014;8(5):473-488 4. Expert Panel on Integrated Guidelines for
Cardiovascular Health and Risk Reduction in Children and Adolescents: Pediatrics. 2011;128;S213
Reference Values:
60-80% of total cholesterol
Reference values have not been established for patients that are <16 years of age.
Clinical References: Glomset JA, Assmann G, Gjone E, Norum KR: Lecithin: cholesterol
acyltransferase deficiency and fish eye disease. In The Metabolic Basis of Inherited Disease. Seventh
edition. Edited by CR Scriver, AL Beaudet, WS Sly, D Valle. New York, McGraw-Hill Book Company,
1995, pp 1933-1951
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the 2 most prevalent forms. Cr(+3) is the only oxidation state present under normal physiologic
conditions. Cr(+6) is widely used in industry to make chromium alloys including stainless steel pigments
and electroplated coatings. Cr(+6), a known carcinogen, is rapidly metabolized to Cr(+3). Cr(+3) is the
only form present in human urine.
Reference Values:
Chromium/creatinine ratio: <10.0 mcg/g creatinine
Clinical References: Centers for Disease Control and Prevention: NIOSH Draft Criteria
Document Update: Occupational Exposure to Hexavalent Chromium September 2008.
DRAFT-Criteria-Document-Update-Occupational-Exposure-to-Hexavalent-Chromium. Retrieved
2/27/09. Available at http://www.cdc.gov/niosh/review/public/144/
Useful For: Screening for occupational exposure to chromium Monitoring metallic prosthetic
implant wear
Interpretation: Chromium is principally excreted in the urine. Urine levels correlate with exposure.
Results greater than the reference range indicate either recent exposure to chromium or specimen
contamination during collection. Prosthesis wear is known to result in increased circulating
concentration of metal ions. Modest increase (8-16 mcg/24 hour) in urine chromium concentration is
likely to be associated with a prosthetic device in good condition. Urine concentrations >20 mcg/24
hour in a patient with chromium-based implant suggest significant prosthesis wear. Increased urine trace
element concentrations in the absence of corroborating clinical information do not independently predict
prosthesis wear or failure. The National Institute for Occupational Safety and Health (NIOSH) draft
document on occupational exposure reviews the data supporting use of urine to assess chromium
exposure. They recommend a Biological Exposure Index of 10 mcg/g creatinine and 30 mcg/g
creatinine for the increase in urinary chromium concentrations during a work shift and at the end of shift
at the end of the workweek, respectively. A test for this specific purpose (CHROMU / Chromium for
Occupational Monitoring, Urine) is available.
Reference Values:
0-15 years: not established
> or =16 years: 0.0-7.9 mcg/specimen
Clinical References: 1. Vincent JB: Elucidating a biological role for chromium at a molecular
level. Acc Chem Res 2000 July;33(7):503-510 2. NIOSH Hexavalent Chromium Criteria Document
Update, September 2008; Available from URL: http://www.cdc.gov/niosh/topics/hexchrom/ 3. Keegan
GM, Learmonth ID, Case CP: A systematic comparison of the actual, potential, and theoretical health
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 509
effects of cobalt and chromium exposures from industry and surgical implants. Crit Rev Toxicol
2008;38:645-674
Useful For: Screening for occupational exposure to chromium Monitoring metallic prosthetic implant
wear
Interpretation: Chromium is principally excreted in the urine. Urine levels correlate with exposure.
Results greater than the reference range indicate either recent exposure to chromium or specimen
contamination during collection. Prosthesis wear is known to result in increased circulating concentration
of metal ions. Modest increase (8-16 mcg/L) in urine chromium concentration is likely to be associated
with a prosthetic device in good condition. Urine concentrations >20 mcg/L in a patient with
chromium-based implant suggest significant prosthesis wear. Increased urine trace element concentrations
in the absence of corroborating clinical information do not independently predict prosthesis wear or
failure. The National Institute for Occupational Safety and Health (NIOSH) draft document on
occupational exposure reviews the data supporting use of urine to assess chromium exposure. They
recommend a Biological Exposure Index of 10 mcg/g creatinine and 30 mcg/g creatinine for the increase
in urinary chromium concentrations during a work shift and at the end of shift at the end of the workweek,
respectively. A test for this specific purpose (CHROMU / Chromium for Occupational Monitoring, Urine)
is available.
Reference Values:
No established reference values
Clinical References: 1. Vincent JB: Elucidating a biological role for chromium at a molecular level.
Acc Chem Res 2000;33(7):503-510 2. NIOSH Hexavalent Chromium Criteria Document Update,
September 2008; Available from URL: http://www.cdc.gov/niosh/topics/hexchrom/ 3. Keegan GM,
Learmonth ID, Case CP: A systematic comparison of the actual, potential, and theoretical health effects of
cobalt and chromium exposures from industry and surgical implants. Crit Rev Toxicol 2008;38:645-674
Useful For: Screening for occupational exposure Monitoring metallic prosthetic implant wear
Interpretation: Results greater than the flagged value indicate clinically significant exposure to
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chromium (Cr) (see Cautions about specimen collection). Prosthesis wear is known to result in increased
circulating concentration of metal ions. Modest increase (0.3-0.6 ng/mL) in serum Cr concentration is
likely to be associated with a prosthetic device in good condition. Serum concentrations >1 ng/mL in a
patient with Cr-based implant suggest significant prosthesis wear. Increased serum trace element
concentrations in the absence of corroborating clinical information do not independently predict
prosthesis wear or failure.
Reference Values:
<0.3 ng/mL
When collected by a phlebotomist experienced in ultra-clean collection technique and handled
according to the instructions in Trace Metals Analysis Specimen Collection and Transport in Special
Instructions, we have observed the concentration of chromium in serum to be <0.3 ng/mL. However, the
majority of specimens submitted for analysis from unexposed individuals contain 0.3 ng/mL to 0.9
ng/mL of chromium. Commercial evacuated blood collection tubes not designed for trace-metal
specimen collection yield serum containing 2.0 ng/mL to 5.0 ng/mL chromium derived from the
collection tube.
Clinical References: 1. Vincent JB: Elucidating a biological role for chromium at a molecular
level. Acc Chem Res 2000 July;33(7):503-510 2. NIOSH Hexavalent Chromium Criteria Document
Update. September 2008; Available from URL: http://www.cdc.gov/niosh/topics/hexchrom/ 3. Keegan
GM, Learmonth ID, Case CP: A systematic comparison of the actual, potential, and theoretical health
effects of cobalt and chromium exposures from industry and surgical implants. Crit Rev Toxicol
2008;38:645-674 4. Tower SS: Arthroprosthetic cobaltism: Neurological and cardiac manifestations in
two patients with metal-on-metal arthroplasty: A case report. J Bone Joint Surg Am 2010;92:1-5
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syndrome, in particular flushing. Finally, a number of tumors that are not derived from classical
endocrine or neuroendocrine tissues, but contain cells with partial neuroendocrine differentiation, such
as small-cell carcinoma of the lung or prostate carcinoma, may also display elevated CGA levels. The
role of CGA measurement is not well defined in these tumors, with the possible exception of prognostic
information in advanced prostate cancer.(5)
Useful For: Follow-up or surveillance of patients with known or treated carcinoid tumors An adjunct
in the diagnosis of carcinoid tumors An adjunct in the diagnosis of other neuroendocrine tumors,
including pheochromocytomas, medullary thyroid carcinomas, functioning and nonfunctioning islet cell
and gastrointestinal amine precursor uptake and decarboxylation tumors, and pituitary adenomas A
possible adjunct in outcome prediction and follow-up in advanced prostate cancer
Reference Values:
<93 ng/mL
Reference values apply to all ages.
Clinical References: 1. Bartolomucci A, Possenti R, Mahata SK, et al: The extended granin family:
Structure, function, and biomedical implications. Endocr Rev 2011;32:755-797 2. Boudreaux JP, Klimstra
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DS, Hassan MM, et al: The NANETS Consensus Guideline for the diagnosis and management of
neuroendocrine tumors-Well-differentiated neuroendocrine tumors of the jejunum, ileum, appendix, and
cecum. Pancreas 2010;39:753-766 3. Anthony LB, Stosberg JR, Klimstra DS, et al: The NANETS
Consensus Guideline for the diagnosis and management of neuroendocrine tumors - Well-differentiated
NETs of the distal colon and rectum. Pancreas 2010;39:767-774 4. Kullke MH, Benson AB, Bergsland E,
et al: National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN
Guidelines): NCCN Guidelines Version 1.2012 - Neuroendocrine Tumors. p 1-94, E-Pub Date 3/20/2012.
URL: http://www.nccn.org/professionals/physician_gls/pdf/neuroendocrine.pdf - last accessed 4/5/2012 -
requires (free) online registration with NCCN 5. Tricoli JV, Schoenfeldt M, Conley BA: Detection of
prostate cancer and predicting progression: Current and future diagnostic markers. Clin Cancer Res
2004;10:3943-3953 6. Algeciras-Schimnich A, Preissner CM, Young WF, et al: Plasma chromogranin A
or urine fractionated metanephrines follow-up testing improves the diagnostic accuracy of plasma
fractionated metanephrines for pheochromocytomas. J Clin Endocrinol Metab 2008;93:91-95 7. Korse
CM, Muller M, Taal BG: Discontinuation of proton pump inhibitors during assessment of chromogranin
A levels in patients with neuroendocrine tumors. Br J Cancer 2011;32:1173-1175 8. Bech PR,
Ramachandran R, Dhillo WS, et al: Quantifying the effects of renal impairment on plasma concentrations
of the neuroendocrine neoplasia biomarkers chromogranin A, chromogranin B, and cocaine- and
amphetamine-regulated transcript. Clin Chem 2012;58:941-943
Useful For: Determining the inheritance pattern of copy number changes previously identified by
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chromosomal microarray analysis in a patient and aiding in the clinical interpretation of the
pathogenicity of the copy number change
Clinical References: 1. Shaffer LG, Kashork CD, Saleki R, et al: Targeted genomic microarray
analysis for identification of chromosome abnormalities in 1500 consecutive clinical cases. J Pediatr 2006
Jul;149(1):98-102 2. Baldwin EL, Lee JY, Blake DM, et al: Enhanced detection of clinically relevant
genomic imbalances using a targeted plus whole genome oligonucleotide microarray. Genet Med 2008
May;10:415-429
Useful For: Prenatal diagnosis of copy number changes (gains or losses) across the entire genome
Diagnosing chromosomal causes for fetal death Determining recurrence risk of future pregnancy losses
Determining the size, precise breakpoints, gene content, and any unappreciated complexity of
abnormalities detected by other methods such as conventional chromosome and FISH studies
Determining if apparently balanced abnormalities identified by previous conventional chromosome
studies have cryptic imbalances, since a proportion of such rearrangements that appear balanced at the
resolution of a chromosome study are actually unbalanced when analyzed by higher-resolution
chromosomal microarray Assessing regions of homozygosity related to uniparental disomy or identical by
descent
Interpretation: Copy number variants are classified based on known, predicted, or possible
pathogenicity and reported with interpretive comments detailing their potential or known significance.
While many copy number changes observed by chromosomal microarray testing can readily be
characterized as pathogenic or benign, there are limited data available to support definitive classification
of a subset into either of these categories, making interpretation of these variants challenging. In these
situations, a number of considerations are taken into account to help interpret results including the size
and gene content of the imbalance, as well as whether the change is a deletion or duplication. Parental
testing may also be necessary to further assess the potential pathogenicity of a copy number change. In
such situations, the inheritance pattern and clinical and developmental history of the transmitting parent
will be taken into consideration. The continual discovery of novel copy number variation and published
clinical reports means that the interpretation of any given copy number change may evolve with increased
scientific understanding. The detection of excess homozygosity may suggest the need for additional
clinical testing to confirm uniparental disomy or to test for mutations in genes associated with autosomal
recessive disorders present in regions of homozygosity.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 514
Reference Values:
An interpretive report will be provided.
Useful For: Diagnosis of congenital copy number changes in products of conception, including
aneuploidy (ie, trisomy or monosomy) and structural abnormalities Diagnosing chromosomal causes for
fetal death Determining recurrence risk of future pregnancy losses Determining the size, precise
breakpoints, gene content, and any unappreciated complexity of abnormalities detected previously by
other methods such as conventional chromosome and FISH studies Determining if apparently balanced
abnormalities identified by previous conventional chromosome studies have cryptic imbalances, since a
proportion of such rearrangements that appear balanced at the resolution of a chromosome study are
actually unbalanced when analyzed by higher-resolution chromosomal microarray
Interpretation: Copy number variants are classified based on known, predicted, or possible
pathogenicity and reported with interpretive comments detailing their potential or known significance.
A normal result will be reported as arr(1-22,X)x2 or arr(1-22)x2,(XY)x1. A copy number change
known to be of clinical significance will be reported as pathogenic. Copy number changes with
unknown significance will be reported as either likely benign, uncertain, or likely pathogenic. Absence
of heterozygosity will be reported. While many copy number changes observed by chromosomal
microarray testing can readily be characterized as pathogenic or benign, there are limited data available
to support definitive classification of a subset into either of these categories, making interpretation of
these variants challenging. In these situations, a number of considerations are taken into account to help
interpret results including the size and gene content of the imbalance, as well as whether the change is a
deletion or duplication. Parental testing may also be necessary to further assess the potential
pathogenicity of a copy number change. In such situations, the inheritance pattern and clinical and
developmental history of the transmitting parent will be taken into consideration. The continual
discovery of novel copy number variation and published clinical reports means that the interpretation of
any given copy number change may evolve with increased scientific understanding. The detection of
excess homozygosity may suggest the need for additional clinical testing to confirm uniparental disomy
or to test for mutations in genes associated with autosomal recessive disorders present in regions of
homozygosity.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 515
Reference Values:
An interpretive report will be provided.
Useful For: First tier, postnatal test for individuals with multiple anomalies that are not specific to
well-delineated genetic syndromes, apparently nonsyndromic developmental delay or intellectual
disability, or autism spectrum disorders as recommended by the American College of Medical Genetics
(ACMG). An appropriate follow-up test for individuals with unexplained developmental delay or
intellectual disability, autism spectrum disorders, or congenital anomalies with a previously normal
conventional chromosome study Determining the size, precise breakpoints, gene content, and any
unappreciated complexity of abnormalities detected by other methods such as conventional chromosome
and FISH studies Determining if apparently balanced abnormalities identified by previous conventional
chromosome studies have cryptic imbalances, since a proportion of such rearrangements that appear
balanced at the resolution of a chromosome study are actually unbalanced when analyzed by
higher-resolution chromosomal microarray. Assessing regions of homozygosity related to uniparental
disomy or identity by descent.
Interpretation: When interpreting results, the following factors need to be considered: Copy number
variation is found in all individuals, including patients with abnormal phenotypes and normal populations.
Therefore, determining the clinical significance of a rare or novel copy number change can be
challenging. Parental testing may be necessary to further assess the potential pathogenicity of a copy
number change. While most copy number changes observed by chromosomal microarray testing can
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 516
readily be characterized as pathogenic or benign, there are limited data available to support definitive
classification of a subset into either of these categories. In these situations, a number of considerations are
taken into account to help interpret results including the size and gene content of the imbalance, whether
the change is a deletion or duplication, the inheritance pattern, and the clinical and/or developmental
history of a transmitting parent. The continual discovery of novel copy number variation and published
clinical reports means that the interpretation of any given copy number change may evolve with increased
scientific understanding. The detection of excessive homozygosity may suggest the need for additional
clinical testing to confirm uniparental disomy or to test for mutations in genes associated with autosomal
recessive disorders consistent with the patient's clinical presentation that are present in regions of
homozygosity. Families benefit from hearing genetic information multiple times and in multiple ways. A
referral to a clinical genetics professional is appropriate for individuals and families to discuss the results
of chromosomal microarray testing.
Reference Values:
An interpretive report will be provided.
Useful For: Detection and characterization of clonal copy number imbalance and loss of
heterozygosity associated with hematologic neoplasms Assisting in the diagnosis and classification of
certain hematologic neoplasms Evaluating the prognosis for patients with certain hematologic
neoplasms
Interpretation: The interpretive report describes copy number changes and any loss of
heterozygosity that may be associated with the neoplastic process. Abnormal clones with subclonal
cytogenetic evolution will be discussed if identified. The continual discovery of novel copy number
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 517
variation and published clinical reports means that the interpretation of any given copy number change
may evolve with increased scientific understanding. Although the presence of a clonal abnormality
usually indicates a neoplasia, in some situations it may reflect a benign or constitutional genetic change.
If a genetic change is identified that is likely constitutional and clearly pathogenic (eg, XYY), follow-up
with a medical genetics consultation may be suggested. The absence of an abnormal clone may be the
result of specimen collection from a site that is not involved in the neoplasm, or may indicate that the
disorder is caused by a point mutation that is not detectable by chromosomal microarray (CMA). CMA,
FISH, and conventional cytogenetics are to some extent complementary methods. In some instances,
additional FISH or conventional cytogenetic studies will be recommended to clarify interpretive
uncertainties.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Cooley L, Lebo M, Li M, et al: American College of Medical Genetics and
Genomics technical standards and guidelines: microarray analysis for chromosome abnormalities in
neoplastic disorders. Genet Med 2013;15:484-494 2. Dougherty M, Wilmoth D, Tooke L, et al:
Implementation of high resolution single nucleotide polymorphism array analysis as a clinical test for
patients with hematologic malignancies. Cancer Genetics 2011;204:26-38 3. Schwartz, S: Clinical Utility
of Single Nucleotide Polymorphism Arrays. Clin Lab Med 2011;31:581-594 4. Braggio E, Kay N,
VanWier S, et al: Longitudinal genome-wide analysis of patients with chronic lymphocytic leukemia
reveals complex evolution of clonal architecture at disease progression and at the time of relapse.
Leukemia 2012;26:1698-1701
Useful For: Prenatal diagnosis of copy number changes (gains or losses) across the entire genome
Determining the size, precise breakpoints, gene content, and any unappreciated complexity of
abnormalities detected by other methods such as conventional chromosome and FISH studies
Determining if apparently balanced abnormalities identified by previous conventional chromosome
studies have cryptic imbalances, since a proportion of such rearrangements that appear balanced at the
resolution of a chromosome study are actually unbalanced when analyzed by higher-resolution
chromosomal microarray Assessing regions of homozygosity related to uniparental disomy or identity by
descent
Interpretation: Copy number variants are classified based on known, predicted, or possible
pathogenicity and reported with interpretive comments detailing their potential or known significance.
When interpreting results it is important to realize that copy number variation is found in all individuals,
including patients with abnormal phenotypes and normal populations. Therefore, determining the clinical
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 518
significance of a rare or novel copy number change can be challenging. Parental testing may be necessary
to further assess the potential pathogenicity of a copy number change. While most copy number changes
observed by chromosomal microarray testing can readily be characterized as pathogenic or benign, there
are limited data available to support definitive classification of a subset into either of these categories. In
these situations, a number of considerations are taken into account to help interpret results including the
size and gene content of the imbalance, whether the change is a deletion or duplication, the inheritance
pattern, and the clinical and developmental history of a transmitting parent. The continual discovery of
novel copy number variation and published clinical reports means that the interpretation of any given
copy number change may evolve with increased scientific understanding. Copy number changes with
unknown significance will be reported when at least 1 gene is involved in a deletion greater than 1
megabases (Mb) or a duplication greater than 2 Mb. The detection of excessive homozygosity may
suggest the need for additional clinical testing to confirm uniparental disomy or to test for mutations in
genes associated with autosomal recessive disorders consistent with the patient's clinical presentation that
are present in regions of homozygosity. Regions with absence of heterozygosity (AOH) with unknown
significance will be reported when greater than 5 Mb (terminal) and 10 Mb (interstitial) on
UPD-associated chromosomes. Whole genome AOH will be reported when greater than 10% of the
genome.
Reference Values:
An interpretive report will be provided.
Useful For: Genomic characterization of tumor for copy number imbalances and loss of
heterozygosity Assisting in the diagnosis and classification of malignant neoplasms Evaluating the
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prognosis for patients with malignant tumors
Interpretation: The interpretive report describes copy number changes and any loss of heterozygosity
that may be associated with the neoplastic process. Abnormal clones with subclonal cytogenetic evolution
will be discussed if identified. The continual discovery of novel copy number variation and published
clinical reports means that the interpretation of any given copy number change may evolve with increased
scientific understanding. Although the presence of a clonal abnormality usually indicates a neoplasia, in
some situations it may reflect a benign or constitutional genetic change. If a genetic change is identified
that is likely constitutional and clearly pathogenic (eg, XYY), follow-up with a medical genetics
consultation may be suggested. The absence of an abnormal clone may be the result of specimen
collection from a site that is not involved in the neoplasm, or may indicate that the disorder is caused by a
point mutation that is not detectable by chromosomal microarray (CMA). CMA, FISH, and conventional
cytogenetics are to some extent complementary methods. In some instances, additional FISH or
conventional cytogenetic studies will be recommended to clarify interpretive uncertainties. See
Cytogenetic Analysis of Glioma in Special Instructions for common questions and answers.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Cooley L, Lebo M, Li M, et al: American College of Medical Genetics and
Genomics technical standards and guidelines: microarray analysis for chromosome abnormalities in
neoplastic disorders. Genet Med 2013;15:484-494 2. Ciriello G, Miller ML, Aksoy BA, et al: Emerging
landscape of oncogenic signatures across human cancers. Nat Genet. 2013 Sep 26;45(10):1127-1133 3.
Wang Y, Cottman M, Schiffman JD. Molecular inversion probes: a novel microarray technology and its
application in cancer research. Cancer Genet 2012 Jul-Aug;205(7-8):341-355
Useful For: Genomic characterization of tumor for copy number imbalances and loss of heterozygosity
Assisting in the diagnosis and classification of malignant neoplasms, including hematolymphoid
malignancies Evaluating the prognosis for patients with malignant tumors
Interpretation: The interpretive report describes copy number changes and any loss of heterozygosity
that may be associated with the neoplastic process. Abnormal clones with subclonal cytogenetic evolution
will be discussed if identified. The continual discovery of novel copy number variation and published
clinical reports means that the interpretation of any given copy number change may evolve with increased
scientific understanding. Although the presence of a clonal abnormality usually indicates a neoplasia, in
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 520
some situations it may reflect a benign or constitutional genetic change. If a genetic change is identified
that is likely constitutional and clearly pathogenic (eg, XYY), follow-up with a medical genetics
consultation may be suggested. The absence of an abnormal clone may be the result of specimen
collection from a site that is not involved in the neoplasm, or may indicate that the disorder is caused by a
point mutation that is not detectable by chromosomal microarray (CMA). CMA, FISH, and conventional
cytogenetics are to some extent complementary methods. In some instances, additional FISH or
conventional cytogenetic studies will be recommended to clarify interpretive uncertainties.
Reference Values:
An interpretive report will be provided.
Useful For: Prenatal diagnosis of chromosome abnormalities, including aneuploidy (ie, trisomy or
monosomy) and balanced rearrangements
Interpretation: Cytogenetic studies on amniotic fluid are considered nearly 100% accurate for the
detection of large fetal chromosome abnormalities. However, subtle or cryptic abnormalities involving
microdeletions usually can be detected only with the use of targeted FISH testing. Approximately 3% of
amniotic fluid specimens analyzed are found to have chromosome abnormalities. Some of these
chromosome abnormalities are balanced and may not be associated with birth defects. A normal
karyotype does not rule out the possibility of birth defects, such as those caused by submicroscopic
cytogenetic abnormalities, molecular mutations, and other environmental factors (ie, teratogen
exposure). For these reasons, clinicians should inform their patients of the technical limitations of
chromosome analysis prior to performing the amniocentesis. It is recommended that a qualified
professional in Medical Genetics communicate all results to the patient.
Reference Values:
An interpretative report will be provided.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 521
CHRPC Chromosome Analysis, Autopsy, Products of Conception, or
35315 Stillbirth
Clinical Information: Chromosome analysis of products of conception, spontaneous abortions,
stillborn infants, or neonates is appropriate when previous losses have occurred and features suggestive of
or concerns for aneuploidy syndromes, including Down syndrome, Turner syndrome, Klinefelter
syndrome, trisomy 13 syndrome and trisomy 18 syndrome. Chromosomal abnormalities may result in
malformed fetuses, spontaneous abortions, or neonatal deaths. Estimates of the frequency of chromosome
abnormalities in spontaneous abortuses range from 15% to 60%. Chromosome studies of products of
conception (POC) may provide useful information concerning the cause of miscarriage and, thus, the
recurrence risk for pregnancy loss and risk for having subsequent children with chromosome anomalies.
Chromosome analysis of the stillborn infant or neonate (autopsy) may be desirable, particularly if there is
a family history of 2 or more miscarriages or when malformations are evident. For neonatal cases,
peripheral blood is the preferred specimen for chromosome analysis (CHRCB / Chromosome Analysis,
Congenital Disorders, Blood). Some of the chromosome abnormalities that are detected in these
specimens are balanced (no apparent gain or loss of genetic material) and may not be associated with birth
defects, miscarriage, or stillbirth. For balanced chromosome rearrangements, it is sometimes difficult to
determine whether the chromosome abnormality is the direct cause of a miscarriage or stillbirth. In these
situations, chromosome studies of the parents' peripheral blood may be useful to determine if an
abnormality is familial or de novo. De novo, balanced rearrangements can cause miscarriages or stillbirth
by producing submicroscopic deletions, duplications, or gene mutations at the site of chromosome
breakage. A normal karyotype does not rule out the possibility of birth defects, such as those caused by
submicroscopic cytogenetic abnormalities, molecular mutations, and environmental factors (ie, teratogen
exposure). -Subtle structural chromosomal abnormalities can occasionally be missed -Culturing of
maternal cells rather than fetal cells -Chromosome mosaicism may be missed due to statistical sampling
error (rare) A chromosomal microarray (CMAP / Chromosomal Microarray, Prenatal, Amniotic
Fluid/Chorionic Villus Sampling) is recommended, rather than chromosomal analysis, to detect clinically
relevant gains or losses of chromosomal material in instances of intrauterine fetal demise or stillbirth.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Laurino MY, Bennett RL, Saraiya DS, et al: Genetic evaluation and
counseling of couples with recurrent miscarriage: recommendations of the National Society of Genetic
Counselors. J Genet Couns 2005;14,165-181 2. American College of Obstetricians and Gynecologists
Committee on Genetics: Committee Opinion No. 581: the use of chromosomal microarray analysis in
prenatal diagnosis. Obstet Gynecol 2013;122:1374-1377 3. Society for Maternal-Fetal Medicine (SMFM):
The use of chromosomal microarray for prenatal diagnosis. Am J Obstet Gynecol. 2016;215:B2-B9
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CHRBF Chromosome Analysis, Body Fluid
35314 Clinical Information: Cytogenetic studies on body fluids (eg, pleural effusions, ascites, and
pericardial, cerebrospinal, and synovial fluids) may be helpful to diagnose or to rule-out metastases or
relapses in patients with lymphoma or other malignancies. Chromosome analysis serves as a useful
adjunct to cytology. In pleural fluids, lymphomas are often more readily diagnosed by cytogenetic
techniques than by standard cytologic examination.
Reference Values:
An interpretive report will be provided.
Clinical References: Dewald GW, Dines DE, Weiland LH, Gordon H: The usefulness of
chromosome examination in the diagnosis of malignant pleural effusions. N Engl J Med
1976;295:1494-1500
Useful For: Prenatal diagnosis of chromosome abnormalities, including aneuploidy (ie, trisomy or
monosomy) and balanced rearrangements This test is not appropriate as a first-tier test for detecting
gains or losses of chromosomal material in pregnancies with one or more major structural
abnormalities.
Interpretation: Cytogenetic studies on chorionic villus specimen (CVS) are considered more than
99% reliable for the detection of most fetal chromosome abnormalities. However, subtle or cryptic
abnormalities involving microdeletions usually can be detected only with the use of targeted FISH
testing. Approximately 3% of CSVs analyzed are found to have chromosome abnormalities. Some of
these chromosome abnormalities are balanced and may not be associated with birth defects. A normal
karyotype does not rule out the possibility of birth defects, such as those caused by submicroscopic
cytogenetic abnormalities, molecular mutations, and environmental factors (ie, teratogen exposure). For
these reasons, clinicians should inform their patients of the technical limitations of chromosome
analysis before the procedure is performed, so that patients may make an informed decision about
pursuing the procedure. Limitations: -False-chromosome mosaicism may occur due to artifact of culture
-True mosaicism may be missed due to statistical sampling error -Presence of chromosome
abnormalities in placental cells that do not occur in the cells of the fetus (confined placental mosaicism)
-Subtle structural chromosome abnormalities can occasionally be missed It is recommended that a
qualified professional in Medical Genetics communicate all results to the patient.
Reference Values:
An interpretive report will be provided.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 523
Clinical References: 1. American College of Obstetricians and Gynecologists Committee on
Genetics: Committee Opinion No. 581: the use of chromosomal microarray analysis in prenatal diagnosis.
Obstet Gynecol 2013;122:1374-1377 2. Society for Maternal-Fetal Medicine (SMFM): The use of
chromosomal microarray for prenatal diagnosis. Am J Obstet Gynecol. 2016;215:B2-B9 3. Committee
Opinion, 640: Cell-free DNA screening for fetal aneuploidy. American College of Obstetricians and
Gynecologists Committee on Genetics. Obstet Gynecol 2015;123:e31-e37 4. Wilson KL, Czerwinski JL,
Hoskovec JM, et al: NSGC practice guideline: prenatal screening and diagnostic testing options for
chromosome aneuploidy. J Genet Couns 2013;22:4-15
Interpretation: When interpreting results, the following factors need to be considered: -Some
chromosome abnormalities are balanced (no apparent gain or loss of genetic material) and may not be
associated with birth defects. However, balanced abnormalities often cause infertility and, when inherited
in an unbalanced fashion, may result in birth defects in the offspring. -A normal karyotype (46,XX or
46,XY with no apparent chromosome abnormality) does not eliminate the possibility of birth defects such
as those caused by submicroscopic cytogenetic abnormalities, molecular mutations, and environmental
factors (ie, teratogen exposure). It is recommended that a qualified professional in Medical Genetics
communicate all abnormal results to the patient.
Reference Values:
An interpretive report will be provided.
Interpretation: When interpreting results, the following factors need to be considered: -Some
chromosome abnormalities are balanced (no apparent gain or loss of genetic material) and may not be
associated with birth defects. However, balanced abnormalities often cause infertility and, when
inherited in an unbalanced fashion, may result in birth defects in the offspring. -A normal karyotype
(46,XX or 46,XY with no apparent chromosome abnormality) does not eliminate the possibility of birth
defects such as those caused by submicroscopic cytogenetic abnormalities, molecular mutations, and
environmental factors (ie, teratogen exposure). -Chromosomal mosaicism may be missed due to
statistical sampling error (rare) -Subtle structural chromosome abnormalities can occasionally be missed
-It is recommended that a qualified professional in Medical Genetics communicate all abnormal results
to the patient.
Reference Values:
An interpretive report will be provided.
Useful For: Assisting in the classification and follow-up of certain malignant hematological disorders
when bone marrow is not available
Interpretation: The presence of an abnormal clone usually indicates a malignant neoplastic process.
The absence of an apparent abnormal clone in blood may result from a lack of circulating abnormal cells
and not from an absence of disease. On rare occasions, the presence of an abnormality may be associated
with a congenital abnormality and, thus, not related to a malignant process. When this situation is
suspected, follow-up with a medical genetics consultation is recommended.
Reference Values:
An interpretative report will be provided.
Clinical References: 1. Dewald GW, Ketterling RP, Wyatt WA, Stupca PJ: Cytogenetic studies in
neoplastic hematologic disorders. In Clinical Laboratory Medicine, Second edition. Edited by KD
McClatchey. Baltimore, Williams and Wilkens, 2002, pp 658-685 2. Rigolin GM, Cibien F, Martinelli S,
et al: Chromosome aberrations detected by conventional karyotyping using novel mitogens in chronic
lymphocytic leukemia with "normal" FISH: correlations with clinicobiological parameters. Blood 2012
Mar 8;119(10):2310-2313
Useful For: Assisting in the diagnosis and classification of certain malignant hematological disorders
Evaluation of prognosis in patients with certain malignant hematologic disorders Monitoring effects of
treatment Monitoring patients in remission
Interpretation: To ensure the best interpretation, it is important to provide some clinical information
to verify the appropriate type of cytogenetic study is performed. The following factors are important when
interpreting the results: -Although the presence of an abnormal clone usually indicates a malignant
neoplastic process, in rare situations, the clone may reflect a benign condition. -The absence of an
abnormal clone may be the result of specimen collection from a site that is not involved in the neoplasm
or may indicate that the disorder is caused by submicroscopic abnormalities that cannot be identified by
chromosome analysis. -On rare occasions, the presence of an abnormality may be associated with a
congenital abnormality that is not related to a malignant neoplastic process. Follow-up with a medical
genetics consultation is recommended. -On occasion, bone marrow chromosome studies are unsuccessful.
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If clinical information has been provided, we may have a FISH study option that could be performed.
Reference Values:
An interpretative report will be provided.
Clinical References: 1. Dewald GW, Ketterling RP, Wyatt WA, Stupca PJ: Cytogenetic studies in
neoplastic hematologic disorders. In Clinical Laboratory Medicine. Second edition. Edited by KD
McClatchey. Baltimore, Williams and Wilkens, 2002, pp 658-685 2. Rigolin GM, Cibien F, Martinelli
S, et al: Chromosome aberrations detected by conventional karyotyping using novel mitogens in chronic
lymphocytic leukemia with "normal" FISH: correlations with clinicobiological parameters. Blood 2012
Mar 8;119(10):2310-2313
Useful For: Assisting in the diagnosis and classification of certain malignant hematological disorders
Evaluating the prognosis of patients with certain malignant hematologic disorders Monitoring effects of
treatment Monitoring patients in remission
Interpretation: To ensure the best interpretation, it is important to provide some clinical information
to verify the appropriate type of cytogenetic study is performed. The following factors are important
when interpreting the results: -Although the presence of an abnormal clone usually indicates a
malignant neoplastic process, in rare situations, the clone may reflect a benign condition. -The absence
of an abnormal clone may be the result of specimen collection from a site that is not involved in the
neoplasm or may indicate that the disorder is caused by submicroscopic abnormalities that cannot be
identified by chromosome analysis. -On rare occasions, the presence of an abnormality may be
associated with a congenital abnormality that is not related to a malignant neoplastic process. Follow-up
with a medical genetics consultation is recommended. -On occasion, bone marrow chromosome studies
are unsuccessful. If clinical information has been provided, we may have a FISH study option that could
be performed.
Reference Values:
An interpretative report will be provided.
Clinical References: 1. Dewald GW, Ketterling RP, Wyatt WA, Stupca PJ: Cytogenetic studies in
neoplastic hematologic disorders. In Clinical Laboratory Medicine. Second edition. Edited by KD
McClatchey. Baltimore, Williams and Wilkens, 2002, pp 658-685 2. Rigolin GM, Cibien F, Martinelli
S, et al: Chromosome aberrations detected by conventional karyotyping using novel mitogens in chronic
lymphocytic leukemia with "normal" FISH: correlations with clinicobiological parameters. Blood 2012
Mar 8;119(10):2310-2313
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abnormalities can help classify the type of lymphoma. For example, t(14;18)(q32;q21.3) involving the
IGH and BCL2 genes is usually indicative of a follicular lymphoma. A translocation between MYC and
IGH genes or a t(8;14)(q24.1;q32) are both associated with Burkitt lymphoma. Cytogenetic studies
often can help distinguish between B-cell and T-cell disorders. Structural abnormalities involving
breakpoints at any immunoglobulin locus is consistent with a B-cell disorder; structural abnormalities
involving breakpoints at a T-cell receptor site are usually associated with a T-cell disorder.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Pierre RV, Dewald GW, Banks PM: Cytogenetic studies in malignant
lymphoma: possible role in staging studies. Cancer Genet Cytogenet 1980;1:257-261 2. Dewald GW,
Jenkins RB: Cytogenetic and molecular genetic studies of patients with monoclonal gammopathies. In
Neoplastic Diseases of Blood. Second edition. Edited by PH Wiernik, GP Canello, RA Kyle, CA Schiffer.
New York, Churchill Livingstone, 1991, pp 427-438
Useful For: Evaluating patients for chromosome instability syndromes, including ataxia telangiectasia
and Nijmegen breakage syndrome
Interpretation: The pattern of chromosome breakage and the number of breaks are compared to a
normal control and an interpretive report is provided.
Reference Values:
An interpretive report will be provided.
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BLOOM Chromosome Analysis, Sister Chromatid Exchange (SCE) for
35317 Bloom Syndrome, Blood
Clinical Information: Sister chromatid exchange analysis is appropriate in individuals with clinical
features suggestive of Bloom syndrome. Bloom syndrome is a genetic disorder associated with various
congenital defects and predisposition to acute leukemia, pulmonary fibrosis, and Hodgkin lymphomas.
Carcinoma also is commonly seen in these patients. Approximately one-fourth to one-half of patients
develop some type of cancer with a mean age of 25 years at onset. The severity and age of onset of
cancer varies among patients. These patients often have prenatal or postnatal growth retardation, short
stature, malar hypoplasia, telangiectatic erythema of the face and other regions, hypo- and
hyperpigmentation, immune deficiencies, occasional mild mental retardation, infertility, and
high-pitched voices. Bloom syndrome is an autosomal recessive disorder caused by mutations in the
BLM gene located at 15q26.1. While multiple mutations have been detected, the use of molecular
testing to diagnose Bloom syndrome is limited in many ethnic groups. Patients with Bloom syndrome
demonstrate a high frequency of chromosome abnormalities when their cells are cultured. Thus,
cytogenetic studies can be helpful to establish a diagnosis. Bloom syndrome results in 2 characteristic
cytogenetic abnormalities. First, the cells are at increased risk for random breaks leading to fragments or
exchanges between nonhomologous chromosomes. Second, cells in these patients have an increased
frequency of sister chromatid exchanges (SCE: exchange of material between homologous
chromosomes) of approximately 10-fold to 20-fold higher than average. This test is diagnostic for
Bloom syndrome. This test cannot be used to identify heterozygote carriers for Bloom syndrome and is
not appropriate as part of a prenatal screening panel. A normal result does not rule out the possibility of
birth defects, such as those caused by chromosomal abnormalities, molecular mutations, and
environmental factors (ie, teratogen exposure). The test does not rule out other numeric or structural
abnormalities. If a constitutional chromosome abnormality is suspected, a separate conventional
cytogenetic study, CHRCB / Chromosome Analysis, for Congenital Disorders, Blood should be
requested.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Dicken CH, Dewald G, Gordon H: Sister chromatid exchanges in Bloom's
syndrome. Arch Dermatol 1978:114;755-760 2. Sanz MM, German J. Bloom's Syndrome. In
GeneReviews. Edited by RA Pagon, MP Adam, HH Ardinger, et al: University of Washington, Seattle;
1993-2014. 2006 Mar 22 (Updated 2013 Mar 28). Accessed 05/22/2013 Available at:
http://www.ncbi.nlm.nih.gov/books/NBK1398/
Interpretation: When interpreting results, the following factors need to be considered: -Some
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 529
chromosome abnormalities are balanced (no apparent gain or loss of genetic material) and may not be
associated with birth defects. However, balanced abnormalities often cause infertility and, when
inherited in an unbalanced fashion, may result in birth defects in the offspring. -A normal karyotype
(46,XX or 46,XY with no apparent chromosome abnormality) does not eliminate the possibility of birth
defects such as those caused by submicroscopic cytogenetic abnormalities, molecular mutations, and
environmental factors (ie, teratogen exposure). It is recommended that a qualified professional in
Medical Genetics communicate all results to the patient.
Reference Values:
An interpretative report will be provided.
Useful For: Assisting in the classification of malignant tumors associated with chromosomal
abnormalities
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Sandberg AA, Turc-Carel C, Gemmell RM: Chromosomes in solid tumors
and beyond. Cancer Res 1988;48:1049-1059 2. Mitelman Database of Chromosome Aberrations and
Gene Fusions in Cancer. Edited by F Mitelman, B Johansson, F Mertens. 2014, Available from URL:
http://cgap.nci.nih.gov/Chromosomes/Mitelman
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 530
products, eg, blood transfusion, sharing of needles by drug addicts. The virus is also found in virtually
every type of human body fluid and is known to be spread through oral and genital contact. HBV can be
transmitted from mother to child during delivery through contact with blood and vaginal secretions; it is
not commonly transmitted transplacentally. After a course of acute illness, HBV persists in approximately
10% of patients. Some of these carriers are asymptomatic, others develop chronic liver disease including
cirrhosis and hepatocellular carcinoma. Hepatitis C: Hepatitis C virus (HCV) is an RNA virus that is a
significant cause of morbidity and mortality worldwide. HCV is transmitted through contaminated blood
or blood products or through other close, personal contacts. It is recognized as the cause of most cases of
posttransfusion hepatitis. HCV shows a high rate of progression (>50%) to chronic disease. In the United
States, HCV infection is quite common, with an estimated 3.5 to 4 million chronic HCV carriers.
Cirrhosis and hepatocellular carcinoma are sequelae of chronic HCV. The following algorithms are
available in Special Instructions: -Testing Algorithm for the Screening and Diagnosis of Hepatitis C
-Chronic Hepatitis C Treatment and Monitoring Algorithm: Interferon-Free Combination Therapy -Viral
Hepatitis Serologic Profiles
Useful For: The diagnosis and evaluation of patients with symptoms of hepatitis with a duration >6
months Distinguishing between chronic hepatitis B and chronic hepatitis C
Interpretation: Interpretation depends on clinical setting. See Viral Hepatitis Serologic Profile in
Special Instructions. Chronic Hepatitis B: Hepatitis B surface antigen (HBsAg) is the first serologic
marker appearing in the serum 6 to 16 weeks following hepatitis B viral infection. In acute cases,
HBsAg usually disappears 1 to 2 months after the onset of symptoms. Persistence of HBsAg for more
than 6 months indicates development of either a chronic carrier state or chronic liver disease.
Anti-hepatitis B core (anti-HBc) appears shortly after the onset of symptoms. The IgM subclass usually
falls to undetectable levels within 6 months, and the IgG subclass may remain for many years. Hepatitis
B surface antibody (anti-HBs) usually appears with the resolution of hepatitis B virus infection after the
disappearance of HBsAg. If HBsAg and anti-HBc (total antibody) are positive and patient's condition
warrants, consider testing for hepatitis Be antigen (HBeAg), anti-HBe, hepatitis B virus DNA
(HBV-DNA) or anti-hepatitis D virus (anti-HDV). Chronic Hepatitis C Virus (HCV): Anti-HCV is
almost always detectable by the late convalescent and chronic stage of infection. The serologic tests
currently available do not differentiate between acute and chronic hepatitis C infections.
Reference Values:
HEPATITIS B SURFACE ANTIGEN
Negative
HEPATITIS C ANTIBODY
Negative
Clinical References: 1. Wietzke P, Schott P, Braun F, et al: Clearance of HCV RNA in a chronic
hepatitis C virus-infected patient during acute hepatitis B virus superinfection. Liver 1999;19:348-353
2. Villari D, Pernice M, Spinella S, et al: Chronic hepatitis in patients with active hepatitis B virus and
hepatitis C virus combined infections: A histological study. Am J Gastroenter 1995;90:955-958 3.
Schmilovitz-Weiss H, Levy M, Thompson N, Dusheiko G: Viral markers in the treatment of hepatitis B
and C. Gut 1993;34:S26-S35
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 531
CHSBP Chronic Hepatitis Profile (Type B)
9023 Clinical Information: Hepatitis B virus (HBV) is a DNA virus that is endemic throughout the world.
The infection is spread primarily through percutaneous contact with infected blood products (eg, blood
transfusion and sharing of needles by drug addicts). The virus is also found in virtually every type of
human body fluid and is known to be spread through oral and genital contact. HBV can be transmitted
from mother to child during delivery through contact with blood and vaginal secretions; it is not
commonly transmitted transplacentally. After a course of acute illness, HBV persists in approximately
10% of patients. Some of these carriers are asymptomatic; others develop chronic liver disease including
cirrhosis and hepatocellular carcinoma. See HBV Infection-Diagnostic Approach and Management
Algorithm and Viral Hepatitis Serologic Profile in Special Instructions.
Useful For: Evaluating patients with suspected or confirmed chronic hepatitis B Monitoring hepatitis B
viral infectivity
Interpretation: Hepatitis B surface antigen (HBsAg) is the first serologic marker appearing in the
serum 6 to 16 weeks following hepatitis B viral (HBV) infection. In acute cases, HBsAg usually
disappears 1 to 2 months after the onset of symptoms. Persistence of HBsAg for more than 6 months
indicates development of either chronic carrier state or chronic liver disease. Hepatitis B surface antibody
(anti-HBs) appears with the resolution of HBV infection after the disappearance of HBsAg. Anti-HBs also
appears as the immune response following a course of inoculation with the hepatitis B vaccine. Hepatitis
B core antibody (anti-HBc) appears shortly after the onset of symptoms of HBV infection and may be the
only serologic marker remaining years after exposure to hepatitis B. The presence of hepatitis B envelope
antigen (HBeAg) correlates with infectivity, the number of viral Dane particles, the presence of core
antigen in the nucleus of the hepatocyte, and the presence of viral DNA polymerase in serum. Hepatitis B
envelope antibody (anti-HBe) positivity in a carrier is often associated with chronic asymptomatic
infection. If the patient has a sudden exacerbation of disease, consider ordering hepatitis C virus antibody
(anti-HCV) and hepatitis delta virus antibody (anti-HDV). If HBsAg converts to negative and patient's
condition warrants, consider testing for anti-HBs. If HBsAg is positive, consider testing for anti-HDV.
See HBV Infection-Diagnostic Approach and Management Algorithm and Viral Hepatitis Serologic
Profiles in Special Instructions.
Reference Values:
HEPATITIS B SURFACE ANTIGEN
Negative
HEPATITIS Be ANTIGEN
Negative
Interpretation depends on clinical setting. See Viral Hepatitis Serologic Profiles in Special Instructions.
Clinical References: 1. Bonino F, Piratvisuth T, Brunetto MR, et al: Diagnostic markers of chronic
hepatitis B infection and disease. Antiviral Therapy 2010;15(3):35-44 2. Servoss JC, Friedman LS:
Serologic and molecular diagnosis of hepatitis B virus. Clin Liver Dis 2004;8:267-281 3. Badur S, Akgun
A: Diagnosis of hepatitis B infections and monitoring of treatment. J Clin Virol 2001;21:229-237
Useful For: Confirming the presence or absence of minimal residual disease in patients with known
chronic lymphocytic leukemia who are either postchemotherapy or post-bone marrow transplantation
Interpretation: An interpretive report for presence or absence of minimal residual disease (MRD)
for chronic lymphocytic leukemia (CLL) is provided. Individuals without CLL should not have
detectable clonal B cells in the peripheral blood or bone marrow. Patients who have detectable MRD by
this assay are considered to have residual CLL disease.
Reference Values:
An interpretive report will be provided.
This test will be processed as a laboratory consultation. An interpretation of the immunophenotypic
findings and correlation with the morphologic features will be provided by a hematopathologist for
every case.
Clinical References: 1. Hallek M, Cheson BD, Catovsky D, et al: Guidelines for the diagnosis and
treatment of chronic lymphocytic leukemia: a report from the International Workshop on chronic
lymphocytic leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood
2008;111:5446-5456 2. Varghese AM, Rawstron AC, Hillmen P: Eradicating minimal residual disease
in chronic lymphocytic leukemia: should this be the goal of treatment? Curr Hematol Malig Rep
2010;5:35-44 3. Shanafelt TD: Predicting clinical outcome in CLL: how and why. Hematology Am Soc
Hematol Educ Program 2009;421-429 4. Sayala HA, Rawstron AC, Hillmen P: Minimal residual
disease assessment in chronic lymphocytic leukaemia. Best Pract Res Clin Haematol 2007;20:499-512
5. Rawstron AC, Villamor N, Ritgen M, et al: International standardized approach for flow cytometric
residual disease monitoring in chronic lymphocytic leukaemia. Leukemia 2007;21:956-964 6. Moreton
P, Kennedy B, Lucas G, et al: Eradication of minimal residual disease in B-cell chronic lymphocytic
leukemia after alemtuzumab therapy is associated with prolonged survival. J Clin Oncol
2005;23:2971-2979
Useful For: Detecting a neoplastic clone associated with the common chromosome abnormalities
seen in patients with chronic lymphocytic leukemia (CLL) Identifying and tracking known chromosome
abnormalities in patients with CLL and tracking response to therapy Distinguishing patients with 11;14
translocations who have leukemic phase of mantle cell lymphoma from patients who have CLL
Detecting patients with atypical CLL or other forms of lymphoma associated with translocations
between IGH and BCL2, BCL3, MYC, or other partner genes
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Interpretation: A neoplastic clone is detected when the percent of cells with an abnormality exceeds
the normal reference range for any given probe set. The absence of an abnormal clone does not rule out
the presence of a neoplastic disorder.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Dewald GW, Brockman SR, Paternoster SF, et al: Chromosome anomalies
detected by interphase FISH: correlation with significant biological features of B-cell chronic
lymphocytic leukemia. Br J Haematol 2003;121:287-295 2. Dohner H, Stilgenbauer S, Benner A, et al:
Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med 2000
Dec;343(26):1910-1916 3. Van Dyke DL, Shanafelt TD, Call TG, et al: A comprehensive evaluation of
the prognostic significance of 13q deletions in patients with B-chronic lymphocytic leukaemia. Br J
Haematol 2010;148:544-550 4. Shanafelt TD: Predicting clinical outcome in CLL: how and why.
Hematology Am Soc Hematol Educ Program 2009;421-429 5. Van Dyke DL, Werner L, Rassenti LZ, et
al: The Dohner fluorescence in situ hybridization prognostic classification of chronic lymphocytic
leukaemia (CLL): the CLL Research Consortium experience. Br J Haematol 2016 Apr;173(1):105-113
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
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Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Reference Values:
No lipoproteins present
Clinical References: Diamond E, Schapira HE: Chyluria-a review of the literature. Urology
1985;26:427-431
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 535
5 50.0-99.9 Strongly positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical utility
of food-specific IgG tests has not been established. These tests can be used in special clinical situations to
select foods for evaluation by diet elimination and challenge in patients who have food-related
complaints. It should be recognized that the presence of food-specific IgG alone cannot be taken as
evidence of food allergy and only indicates immunologic sensitization by the food allergen in question.
This test should only be ordered by physicians who recognize the limitations of the test.
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
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0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Reference Values:
Negative <20 EU/mL
Borderline/Equivocal 20 25 EU/mL
Positive >25 EU/mL
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Cristofanilli M, Budd GT, Ellis MJ, et al: Circulating tumor cells, disease
progression, and survival in metastatic breast cancer. N Engl J Med 2004;351:781-791 2. Allard WJ,
Matera J, Miller MC, et al: Tumor cells circulate in the peripheral blood of all major carcinomas but not
in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res 2004 Oct 15;10:6897-6904
3. Cristofanilli M, Hayes DF, Budd GT, et al: Circulating tumor cells: a novel prognostic factor for
newly diagnosed metastatic breast cancer. J Clin Oncol 2006 Mar 1;23:1420-1430
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Allard WJ, Matera J, Miller MC, et al: Tumor cells circulate in the
peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant
diseases. Clin Cancer Res 2004 Oct;10:6897-6904 2. Cohen SJ, Punt CJ, Iannotti N, et al: Relationship of
circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with
metastatic colorectal cancer. J Clin Oncol 2008 Jul;26(19):3213-3221 3. Cohen SJ, Punt CJ, Iannotti N, et
al: Prognostic significance of circulating tumor cells in patients with metastatic colorectal cancer. Ann
Oncol 2009;20(7):1223-1229
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Allard WJ, Matera J, Miller MC, et al: Tumor cells circulate in the
peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant
diseases. Clin Cancer Res 2004 Oct;10:6897-6904 2. deBono JS, Scher HI, Montgomery RB, et al:
Circulating tumor cells predict survival benefit from treatment in the metastatic castration-resistant
prostate cancer. Clin Cancer Res 2008 October 1;14(19):6302-6309 3. Danila DC, Heller G, Gignac GA,
et al: Circulating tumor cell number and prognosis in progressive castration-resistant prostate cancer. Clin
Cancer Res 2007 December 1;13(23):7053-7058
Useful For: Monitoring citalopram therapy Identifying noncompliance, although regular blood level
monitoring is not indicated in most patients Identifying states of altered drug metabolism when used in
conjunction with CYP2C19 and CYP3A4-5 genotyping
Reference Values:
50-110 ng/mL
Useful For: Diagnosing risk factors for patients with calcium kidney stones Monitoring results of
therapy in patients with calcium stones or renal tubular acidosis
Interpretation: Any value less than the mean for 24 hours represents a potential risk for kidney
stone formation and growth. Patients with low urinary citrate, and new or growing stone formation, may
benefit from adjustments in therapy known to increase urinary citrate excretion. (See Clinical
Information) Very low levels (<150 mg/24 hours) suggest investigation for the possible diagnosis of
metabolic acidosis (eg, renal tubular acidosis).
Reference Values:
0-19 years: not established
20 years: 150-1,191 mg/24 hours
21 years: 157-1,191 mg/24 hours
22 years: 164-1,191 mg/24 hours
23 years: 171-1,191 mg/24 hours
24 years: 178-1,191 mg/24 hours
25 years: 186-1,191 mg/24 hours
26 years: 193-1,191 mg/24 hours
27 years: 200-1,191 mg/24 hours
28 years: 207-1,191 mg/24 hours
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 539
29 years: 214-1,191 mg/24 hours
30 years: 221-1,191 mg/24 hours
31 years: 228-1,191 mg/24 hours
32 years: 235-1,191 mg/24 hours
33 years: 242-1,191 mg/24 hours
34 years: 250-1,191 mg/24 hours
35 years: 257-1,191 mg/24 hours
36 years: 264-1,191 mg/24 hours
37 years: 271-1,191 mg/24 hours
38 years: 278-1,191 mg/24 hours
39 years: 285-1,191 mg/24 hours
40 years: 292-1,191 mg/24 hours
41 years: 299-1,191 mg/24 hours
42 years: 306-1,191 mg/24 hours
43 years: 314-1,191 mg/24 hours
44 years: 321-1,191 mg/24 hours
45 years: 328-1,191 mg/24 hours
46 years: 335-1,191 mg/24 hours
47 years: 342-1,191 mg/24 hours
48 years: 349-1,191 mg/24 hours
49 years: 356-1,191 mg/24 hours
50 years: 363-1,191 mg/24 hours
51 years: 370-1,191 mg/24 hours
52 years: 378-1,191 mg/24 hours
53 years: 385-1,191 mg/24 hours
54 years: 392-1,191 mg/24 hours
55 years: 399-1,191 mg/24 hours
56 years: 406-1,191 mg/24 hours
57 years: 413-1,191 mg/24 hours
58 years: 420-1,191 mg/24 hours
59 years: 427-1,191 mg/24 hours
60 years: 434-1,191 mg/24 hours
>60 years: not established
Clinical References: Hosking DH, Wilson JW, Liedtke RR, et al: The urinary excretion of citrate in
normal persons and patients with idiopathic calcium urolithiasis (abstract). Urol Res 1984;12:26
Useful For: Diagnosing risk factors for patients with calcium kidney stones. Monitoring results of
therapy in patients with calcium stones or renal tubular acidosis. A timed 24-hour urine collection is the
preferred specimen for measuring and interpreting this urinary analyte. Random collections normalized to
urinary creatinine may be of some clinical use in patients who cannot collect a 24-hour specimen,
typically small children. Therefore, this random test is offered for children <16 years old.
Interpretation: A low value represents a potential risk for kidney stone formation/growth. Patients
with low urinary citrate, and new or growing stone formation may benefit from adjustments in therapy
known to increase urinary citrate excretion. Very low levels suggest investigation for the possible
diagnosis of metabolic acidosis (eg, renal tubular acidosis). For children ages 5 to 18, a ratio of <0.176 mg
citrate/ mg creatinine is below the 5% reference range and considered low.(1)
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 540
Reference Values:
No established reference values
Clinical References: 1. Srivastava T, Winston MJ, Auron A et al: Urine calcium/citrate ratio in
children with hypercalciuric stones. Pediatr Res 2009;66:85-90 2. Hosking DH, Wilson JW, Liedtke
RR, et al: The urinary excretion of citrate in normal persons and patients with idiopathic calcium
urolithiasis (abstract). Urol Res 1984;12:26
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
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6 > or =100 Strongly positive Reference values
apply to all ages.
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: An aid in the identification of a number of different soft tissue and epithelial neoplasms
Interpretation: This test includes only technical performance of the stain (no pathologist
interpretation is performed). If diagnostic consultation by a pathologist is required order 70012 /
Pathology Consultation. The positive and negative controls are verified as showing appropriate
immunoreactivity. If a control tissue is not included on the slide, a scanned image of the relevant quality
control tissue is available upon request. Please contact 1-855-516-8404. Interpretation of this test should
be performed in the context of the patient's clinical history and other diagnostic tests by a qualified
pathologist.
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response and may predispose the patient to greater risk of adverse side affects. A toxic range has not
been well established at this time.
Reference Values:
CLOMIPRAMINE AND NORCLOMIPRAMINE
Therapeutic concentration: 230-450 ng/mL
Note: Therapeutic ranges are for specimens drawn at trough (ie, immediately before next scheduled
dose). Levels may be elevated in non-trough specimens.
Clinical References: 1. Wille SM, Cooreman SG, Neels HM, Lambert WE: Relevant issues in the
monitoring and the toxicology of antidepressants. Crit Rev Clin Lab Sci 2008;45(1):25-89 2. Thanacoody
HK, Thomas SH: Antidepressant poisoning. Clin Med 2003;3(2):114-118 3. Hiemke C, et.al: AGNP
Concensus Guidelines for Therapeutic Drug Monitoring in Psychiatry: Update 2011. Pharmacopsychiatry
2011;44(6):195-235 4. Burtis CA, Ashwood ER, Bruns DE. (2012) Tietz Textbook of Clinical Chemistry
and Molecular Diagnostics: Fifth Edition, Elsevier
Useful For: Assessing compliance Monitoring for appropriate therapeutic level Assessing toxicity
Interpretation: The therapeutic range varies depending on the indication. Some individuals may
respond well outside of these ranges, or may display toxicity within the therapeutic range, thus
interpretation should include clinical evaluation. The possibility of toxicity is increased when levels
exceed 100 ng/mL. Therapeutic ranges are based on specimens drawn at trough (ie, immediately before
the next dose).
Reference Values:
Clonazepam
Anticonvulsant: 20-70 ng/mL
Anxiolytic: 4-80 ng/mL
Some individuals may show therapeutic response outside of these ranges, or may display toxicity within
the therapeutic range, thus interpretation should include clinical evaluation.
Note: Therapeutic ranges are for specimens drawn at trough (ie, immediately before next scheduled
dose). Levels may be elevated in non-trough specimens.
Clinical References: Hiemke C, Baumann P, Bergemann N, et al: AGNP Consensus Guidelines for
Therapeutic Drug Monitoring in Psychiatry: Update 2011. Pharmacopsychiatry 2011;44(6):195-235
Sedation has been associated with serum clonidine concentrations greater than 1.5 ng/mL
Useful For: Clostridium difficile culture provides an isolate suitable for antimicrobial susceptibility
testing.
Interpretation: A positive result indicates the presence of viable Clostridium difficile in stool. A
positive culture may be found with asymptomatic Clostridium difficile colonization with a
toxin-producing or non-toxin-producing strain, or with Clostridium difficile-associated diarrhea. A
negative result indicates the absence of Clostridium difficile growth in culture. Isolation of Clostridium
difficile does not differentiate between toxin-producing and non-toxin-producing strains.
Reference Values:
No growth after 1 day of incubation.
Clinical References: Cohen SH, Gerding DN, Johnson S, et al: Clinical practice guidelines for
Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of
America (SHEA) and the infectious diseases society of America (IDSA). Infect Control Hosp
Epidemiol 2010;31(5):431-455
Useful For: Sensitive, specific, and rapid diagnosis of Clostridium difficile-associated diarrhea and
pseudomembranous colitis
Interpretation: A positive PCR result for the presence of the gene regulating toxin production (tcdC)
indicates the presence of Clostridium difficile and toxin A and/or B. A negative result indicates the
absence of detectable Clostridium difficile tcdC DNA in the specimen, but does not rule-out Clostridium
difficile infection. False-negative results may occur due to inhibition of PCR, sequence variability
underlying the primers or probes, or the presence of Clostridium difficile in quantities less than the limit
of detection of the assay.
Reference Values:
Not applicable
Clinical References: 1. Aichinger E, Schleck CD, Harmsen WS, et al: Nonutility of repeat
laboratory testing for detection of Clostridium difficile by use of PCR or enzyme immunoassay. J Clin
Microbiol 2008;46:3795-3797 2. Sloan LM, Duresko BJ, Gustafson DR, et al: Comparison of real-time
PCR for detection of the tcdC gene with four toxin immunoassays and culture in diagnosis of Clostridium
difficile infection. J Clin Microbiol 2008;46:1996-2001 3. Verdoorn BP, Orenstein R, Rosenblatt JE, et al:
High prevalence of tcdC deletion-carrying Clostridium difficile and lack of association with disease
severity. Diagn Microbiol Infect Dis 2010;66:24-28 4. Karre T, Sloan L, Patel R, et al: Comparison of two
commercial molecular assays to a laboratory-developed molecular assay for diagnosis of Clostridium
difficile infection. J Clin Microbiol 2011;49:725-727
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
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3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: Monitoring patient compliance An aid to achieving desired plasma levels
Interpretation: The effectiveness of clozapine treatment should be based on clinical response and
treatment should be discontinued in patients failing to show an acceptable clinical response.
Reference Values:
CLOZAPINE
Therapeutic range: >350 ng/mL
CLOZAPINE + NORCLOZAPINE
Therapeutic range: >450 ng/mL
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 547
and norclozapine plasma concentrations and clinical response of treatment-refractory schizophrenia
patients. Am J Psychiatry 1991;40(5);722-747 4. Physicians Desk Reference (PDR) 2007 5. Fitton
A, Heel RC: Clozapine. A review of its pharmacological properties, and therapeutic use in
schizophrenia. Drugs 1991;40(5);722-747 6. Package insert: Clozaril. East Hanover, NJ: Novartis
Pharmaceuticals; May 2005 7. Mitchell PB: Therapeutic drug monitoring of psychotropic medications.
Br J Clin Pharmacol 2001;52(Suppl 1):45S-54S
Clinical References: 1. Grogg KL, Lae ME, Kurtin PJ, Macon WR: Clusterin expression
distinguishes follicular dendritic cell tumors from other dendritic cell neoplasms. Am J Surg Pathol
2004;28(8):988-998 2. Grogg KL, Macon WR, Kurtin PJ, Nascimento AG: A survey of clusterin and
fascin expression in sarcomas and spindle cell neoplasms: Strong Clusterin Immunostaining is Highly
Specific for Follicular Dendritic Cell Tumor. Modern Pathology 2005;18:260-266 3. Saffer H, Wahed A,
Rassidakis GZ, Medieros J: Clusterin expression in malignant lymphomas: A Survey of 266 Cases.
Modern Pathology 2002;15(11):1221-1226
Useful For: Aids in the identification of normal and neoplastic c-Met expressing cells
Clinical References: 1. Knudsen BS, Zhao P, Resau J, et al: A Novel Multipurpose Monoclonal
Antibody for Evaluating Human c-Met Expression in Preclinical and Clinical Settings. Appl
Immunohistochem Mol Morphol 2009;17(1):57-67 2. Nakamura Y, Niki T, Goto A, et al: c-Met
activation in lung adenocarcinoma tissues: An immunohistochemical analysis. Cancer Sci
2007;98(7):1006-1013 3. Christensen JG, Burrows J, Salgia R: c-Met as a target for human cancer and
characterization of inhibitors for therapeutic intervention. Cancer Letters 2005;225:1-26
This test employs real-time PCR amplification of a Cytomegalovirus-specific conserved genetic target.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 548
A positive result should be coupled with clinical indicators for diagnosis. A Not detected" result for
this assay does not exclude Cytomegalovirus involvement in a disease process.
Useful For: Diagnosing a congenital deficiency (rare) of coagulation factor II Evaluating acquired
deficiencies associated with liver disease or vitamin K deficiency, oral anticoagulant therapy, and
antibody-induced deficiencies (eg, in association with lupus-like anticoagulant) Determining warfarin
treatment stabilization in patients with nonspecific inhibitors (ie, lupus anticoagulant) Determining
degree of anticoagulation with warfarin to correlate with level of protein S Investigation of prolonged
prothrombin time or activated partial thromboplastin time
Interpretation: Liver disease, vitamin K deficiency, or warfarin anticoagulation can cause decreased
factor II activity. Homozygotes generally have levels of <25% Heterozygotes generally have levels of
<50% Normal newborn infants may have levels of 25% to 50%
Reference Values:
Adults: 75-145%
Normal, full-term newborn infants or healthy premature infants may have decreased levels (> or
=25%) which may remain below adult levels for > or =180 days postnatal.*
*See Pediatric Hemostasis References in Coagulation Studies in Special Instructions.
Reference Values:
FACTOR II ACTIVITY ASSAY
Adults: 75-145%
Normal, full-term newborn infants or healthy premature infants may have decreased levels (> or
=25%) which may remain below adult levels for > or =180 days postnatal.*
*See Pediatric Hemostasis References in Coagulation Studies in Special Instructions.
Useful For: Diagnosing deficiencies, particularly hemophilia B (Christmas disease) Assessing the
impact of liver disease on hemostasis Investigation of a prolonged activated partial thromboplastin time
Interpretation: Acquired deficiency is more common than congenital. Mild hemophilia B: 5% to 50%
Moderate hemophilia B: 1% to 5% Severe hemophilia B: <1%
Reference Values:
Adults: 65-140%
Normal, full-term newborn infants or healthy premature infants may have decreased levels (> or =20%)
which may not reach adult levels for > or =180 days postnatal.*
*See Pediatric Hemostasis References in Coagulation Studies in Special Instructions.
Clinical References: 1. Barrowcliffe TW, Raut S, Sands D, Hubbard AR: Coagulation and
chromogenic assays of factor VIII activity: general aspects, standardization, and recommendations. Semin
Thromb Hemost 2002 Jun;28(3):247-256 2. Franchini M, Lippi G, Favaloro EJ: Acquired inhibitors of
coagulation factors: part II. Semin Thromb Hemost 2012 Jul;38(5):447-453 3. Carcao MD: The diagnosis
and management of congenital hemophilia. Semin Thromb Hemost 2012 Oct;38(7):727-734
Useful For: Diagnosing congenital deficiencies (rare) of coagulation factor V Evaluating acquired
deficiencies associated with liver disease, factor V inhibitors, myeloproliferative disorders, and
intravascular coagulation and fibrinolysis Investigation of prolonged prothrombin time or activated partial
thromboplastin time
Interpretation: See Cautions Acquired deficiencies are much more common than congenital (see
Useful For). Congenitally deficient homozygotes generally have levels < or =10% to 20%. Congenitally
deficient heterozygotes generally have levels < or =50%. Congenital deficiency may occur in combined
association with factor VIII deficiency.
Reference Values:
Adults: 70-165%
Normal, full-term newborn infants may have borderline low or mildly decreased levels (> or =30% to
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35%) which reach adult levels within 21 days postnatal. Healthy premature infants (30-36 weeks
gestation) may have borderline low or mildly decreased levels.*
*See Pediatric Hemostasis References in Coagulation Studies in Special Instructions.
Reference Values:
FACTOR V ACTIVITY ASSAY
Adults: 75-165%
Normal, full-term newborn infants may have borderline low or mildly decreased levels (> or
=30-35%) which reach adult levels within 21 days postnatal.*
Healthy premature infants (30-36 weeks gestation) may have borderline low or mildly decreased
levels.*
*See Pediatric Hemostasis References in Coagulation Studies in Special Instructions.
Useful For: Diagnosing congenital deficiency of coagulation factor VII Evaluating acquired
deficiencies associated with liver disease, oral anticoagulant therapy, and vitamin K deficiency
Determining degree of anticoagulation with warfarin to correlate with level of protein C Investigation of
a prolonged prothrombin time
Interpretation: Liver disease, vitamin K deficiency, or warfarin anticoagulation can cause decreased
factor VII activity. Heterozygotes generally have levels of < or =50%. Homozygotes have levels usually
<20%. Newborn infants usually have levels > or =25%.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 551
Reference Values:
Adults: 65-180%
Normal, full-term newborn infants or healthy premature infants may have decreased levels (> or =20%)
which increase within the first postnatal week but may not reach adult levels for > or =180 days
postnatal.*
Reference Values:
FACTOR VII ACTIVITY ASSAY
Adults: 65-180%
Normal, full-term newborn infants or healthy premature infants may have decreased levels (> or =20%)
which increase within the first postnatal week but may not reach adult levels for > or =180 days
postnatal.*
*See Pediatric Hemostasis References in Coagulation Studies in Special Instructions.
Useful For: Diagnosing hemophilia A Diagnosing von Willebrand disease when measured with the
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 552
von Willebrand factor (VWF) antigen and VWF activity Diagnosing acquired deficiency states
Investigation of prolonged activated partial thromboplastin time
Reference Values:
Adults: 55-200%
Normal, full-term newborn infants or healthy premature infants usually have normal or elevated factor
VIII.*
*See Pediatric Hemostasis References in Coagulation Studies in Special Instructions.
Reference Values:
Adults: 70-150%
Normal, full-term newborn infants or healthy premature infants may have decreased levels (> or
=15-20%) which may not reach adult levels for > or =180 days postnatal.*
*See Pediatric Hemostasis References in Coagulation Studies in Special Instructions.
Useful For: Monitoring warfarin anticoagulant therapy, especially in patients whose plasma contains
lupus anticoagulants that interfere with baseline prothrombin time/international normalized ratio and in
patients receiving the drug Argatroban who are being transitioned to warfarin
Reference Values:
> or =18 years of age: 60%-140%
Chromogenic Factor X activity generally correlates with the one-stage factor X activity. In full term or
premature neonates, infants, and children, the one-stage factor X activity* is lower than adult reference
range and progressively rises to the adult reference range by adolescence. However, no similar data for
the chromogenic factor X activity have been published.
*See Pediatric Hemostasis References in Coagulation Studies in Special Instructions.
Clinical References: 1. Austin JH, Stearns CR, Winkler AM, et al: Use of the chromogenic factor X
assay in patients transitioning from Argatroban to warfarin therapy. Pharmacotherapy 2012;32(6):493-501
2. McGlasson DL, Romick BG, Rubal BJ: Comparison of a chromogenic factor x assay with international
normalized ratio for monitoring oral anticoagulation therapy. Blood Coagul Fibrinolysis 2008;19:513-517
3. Moll S, Ortel TL: Monitoring warfarin therapy in patients with lupus anticoagulants. Ann Intern Med
1997;127:177-185 4. Robert A, Le Querrec A, Delahousse B, et al: Control of oral anticoagulation in
patients with antiphospholipid syndrome--influence of the lupus anticoagulant on International
Normalized Ratio. Thromb Haemost 1998;80:99-103
Reference Values:
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 554
FACTOR X ACTIVITY ASSAY
Adults: 70-150%
Normal, full-term newborn infants or healthy premature infants may have decreased levels (> or
=15-20%) which may not reach adult levels for > or =180 days postnatal.*
*See Pediatric Hemostasis References in Coagulation Studies in Special Instructions.
Interpretation: Acquired deficiency is associated with liver disease and rarely inhibitors.
Homozygotes: <20% Heterozygotes: 20% to 60%
Reference Values:
Adults: 55-150%
Normal, full-term newborn infants or healthy premature infants may have decreased levels (> or
=10%) which may not reach adult levels for > or =180 days postnatal.*
*See Pediatric Hemostasis References in Coagulation Studies in Special Instructions.
Reference Values:
FACTOR XI ACTIVITY ASSAY
Adults: 55-150%
Normal, full-term newborn infants or healthy premature infants may have decreased levels (> or
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 555
=10%) which may not reach adult levels for > or =180 days postnatal.*
*See Pediatric Hemostasis References in Coagulation Studies in Special Instructions.
Useful For: Diagnosing deficiency of coagulation factor XII Determining cause of prolonged activated
partial thromboplastin time
Interpretation: Acquired deficiency is associated with liver disease, nephritic syndrome, and chronic
granulocytic leukemia. Congenital homozygous deficiency: 20% Congenital heterozygous deficiency:
20% to 50%
Reference Values:
Adults: 55-180%
Normal, full-term newborn infants or healthy premature infants may have decreased levels (> or =15%
to 20%) which may not reach adult levels for > or =180 days postnatal.*
*See Pediatric Hemostasis References in Coagulation Studies in Special Instructions.
Clinical References: Renne T, Schmaier AH, Nickel KF, et al: In vivo roles of factor XII. Blood
2012 Nov 22;120(22):4296-4303
Useful For: Detecting cobalt exposure Monitoring metallic prosthetic implant wear
Interpretation: Concentrations > or =2.0 mcg/specimen indicate excess exposure. There are no
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 556
Occupational Safety and Health Administration (OSHA) blood or urine criteria for occupational exposure
to cobalt. Prosthesis wear is known to result in increased circulating concentration of metal ions. In a
patient with a cobalt-based implant, modest increase (2-4 mcg/specimen) in urine cobalt concentration is
likely to be associated with a prosthetic device in good condition. Excessive exposure is indicated when
urine cobalt concentration is >5 mcg/specimen, consistent with prosthesis wear. Urine concentrations >20
mcg/specimen in a patient with a cobalt-based implant suggest significant prosthesis wear. Increased urine
trace element concentrations in the absence of corroborating clinical information do not independently
predict prosthesis wear or failure.
Reference Values:
0.0-1.9 mcg/specimen
Reference values apply to all ages.
Clinical References: 1. Keegan GM, Learmonth ID, Case CP: A systematic comparison of the
actual, potential, and theoretical health effects of cobalt and chromium from industry and surgical
implants. Crit Rev Toxicol 2008;38:645-674 2. Lhotka C, Szekes T, Stefan I, et al: Four-year study of
cobalt and chromium blood levels in patients managed with two different metal-on-metal total hip
replacements. J Orthop Res 2003;21:189-195 3. Lison D, De Boeck M, Verougstraete V,
Kirsch-Volders M: Update on the genotoxicity and carcinogenicity of cobalt ompounds. Occup Environ
Med 2001;58(10):619-625
Useful For: Detecting cobalt exposure Monitoring metallic prosthetic implant wear
Interpretation: Concentrations > or =2.0 mcg/L indicate excess exposure. There are no
Occupational Safety and Health Administration (OSHA) blood or urine criteria for occupational
exposure to cobalt. Prosthesis wear is known to result in increased circulating concentration of metal
ions. In a patient with a cobalt-based implant, modest increase (2-4 mcg/L) in urine cobalt concentration
is likely to be associated with a prosthetic device in good condition. Excessive exposure is indicated
when urine cobalt concentration is >5 mcg/L, consistent with prosthesis wear. Urine concentrations >20
mcg/L in a patient with a cobalt-based implant suggest significant prosthesis wear. Increased urine trace
element concentrations in the absence of corroborating clinical information do not independently predict
prosthesis wear or failure.
Reference Values:
0.0-1.9 mcg/L
Reference values apply to all ages.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 557
Clinical References: 1. Keegan GM, Learmonth ID, Case CP: A systematic comparison of the
actual, potential, and theoretical health effects of cobalt and chromium from industry and surgical
implants. Crit Rev Toxicol 2008;38:645-674 2. Lhotka C, Szekes T, Stefan I, et al: Four-year study of
cobalt and chromium blood levels in patients managed with two different metal-on-metal total hip
replacements. J Orthop Res 2003;21:189-195 3. Lison D, De Boeck M, Verougstraete V, Kirsch-Volders
M: Update on the genotoxicity and carcinogenicity of cobalt compounds. Occup Environ Med
2001;58(10):619-625
Useful For: Detecting cobalt toxicity Monitoring metallic prosthetic implant wear
Interpretation: Concentrations > or =1.0 ng/mL indicate possible environmental or occupational
exposure. Cobalt concentrations associated with toxicity must be interpreted in the context of the source
of exposure. If cobalt is ingested, concentrations > 5 ng/mL suggest major exposure and likely toxicity. If
cobalt exposure is due to orthopedic implant wear, there are no large case number reports associating high
circulating serum cobalt with toxicity. There are no Occupational Health and Safety Administration
(OSHA) blood or urine criteria for occupational exposure to cobalt. Prosthesis wear is known to result in
increased circulating concentration of metal ions. Modest increase (4-10 ng/mL) in serum cobalt
concentration is likely to be associated with a prosthetic device in good condition. Serum concentrations
>10 ng/mL in a patient with cobalt-based implant suggest significant prosthesis wear. Increased serum
trace element concentrations in the absence of corroborating clinical information do not independently
predict prosthesis wear or failure.
Reference Values:
0.0-0.9 ng/mL
<10 ng/mL (MoM implant)
Reference values apply to all ages.
Useful For: Detecting cobalt exposure Monitoring metallic prosthetic implant wear
Interpretation: Concentrations > or =2.0 mcg/g creatinine indicate excess exposure. There are no
Occupational Safety and Health Administration (OSHA) blood or urine criteria for occupational
exposure to cobalt. Prosthesis wear is known to result in increased circulating concentration of metal
ions. In a patient with a cobalt-based implant, modest increase (2-4 mcg/g creatinine) in urine cobalt
concentration is likely to be associated with a prosthetic device in good condition. Excessive exposure is
indicated when urine cobalt concentration is >5 mcg/g creatinine, consistent with prosthesis wear. Urine
concentrations >20 mcg/g creatinine in a patient with a cobalt-based implant suggest significant
prosthesis wear. Increased urine trace element concentrations in the absence of corroborating clinical
information do not independently predict prosthesis wear or failure.
Reference Values:
0.0-1.9 mcg/g Creatinine
Reference values apply to all ages.
Clinical References: 1. Keegan GM, Learmonth ID, Case CP: A systematic comparison of the
actual, potential, and theoretical health effects of cobalt and chromium from industry and surgical
implants. Crit Rev Toxicol 2008;38:645-674 2. Lhotka C, Szekes T, Stefan I, et al: Four-year study of
cobalt and chromium blood levels in patients managed with two different metal-on-metal total hip
replacements. J Orthop Res 2003;21:189-195 3. Lison D, De Boeck M, Verougstraete V,
Kirsch-Volders M: Update on the genotoxicity and carcinogenicity of cobalt compounds. Occup
Environ Med 2001;58(10):619-625
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Clinical Information: Cocaine is an alkaloid found in Erythroxylon coca, which grows principally in
the northern South American Andes and to a lesser extent in India, Africa, and Java.(1) Cocaine is a
powerfully addictive stimulant drug. Cocaine abuse has a long history and is rooted into the drug culture
in the United States,(2) and is one of the most common illicit drugs of abuse.(3,4) Cocaine is rapidly
metabolized primarily to benzoylecgonine, which is further metabolized to m-hydroxybenzoylecgonine
(m-HOBE).(1,5) Cocaine is frequently used with other drugs, most commonly ethanol, and the
simultaneous use of both drugs can be determined by the presence of the unique metabolite
cocaethylene.(4) Intrauterine drug exposure to cocaine has been associated with placental abruption,
premature labor, small for gestational age status, microcephaly, and congenital anomalies (eg, cardiac and
genitourinary abnormalities, necrotizing enterocolitis, and central nervous system stroke or
hemorrhage).(6) The disposition of drug in meconium, the first fecal material passed by the neonate, is not
well understood. The proposed mechanism is that the fetus excretes drug into bile and amniotic fluid.
Drug accumulates in meconium either by direct deposition from bile or through swallowing of amniotic
fluid.(7) The first evidence of meconium in the fetal intestine appears at approximately the 10th to 12th
week of gestation, and slowly moves into the colon by the 16th week of gestation.(8) Therefore, the
presence of drugs in meconium has been proposed to be indicative of in utero drug exposure during the
final 4 to 5 months of pregnancy, a longer historical measure than is possible by urinalysis.(7) Chain of
custody is a record of the disposition of a specimen to document who collected it, who handled it, and
who performed the analysis. When a specimen is submitted in this manner, analysis will be performed in
such a way that it will withstand regular court scrutiny.
Useful For: Detection of in utero drug exposure up to 5 months before birth Chain of custody is
required whenever the results of testing could be used in a court of law. Its purpose is to protect the rights
of the individual contributing the specimen by demonstrating that it was under the control of personnel
involved with testing the specimen at all times; this control implies that the opportunity for specimen
tampering would be limited. Since the evidence of illicit drug use during pregnancy can be cause for
separating the baby from the mother, a complete chain of custody ensures that the test results are
appropriate for legal proceedings.
Reference Values:
Negative
Positives are reported with a quantitative LC-MS/MS result.
Cutoff concentrations
Cocaine by LC-MS/MS: 50 ng/g
Benzoylecgonine by LC-MS/MS: 50 ng/g
Cocaethylene by LC-MS/MS: 50 ng/g
m-Hydroxybenzoylecgonine by LC-MS/MS: 50 ng/g
Useful For: Detecting and confirming drug abuse involving cocaine Chain of custody is required
whenever the results of testing could be used in a court of law. Its purpose is to protect the rights of the
individual contributing the specimen by demonstrating that it was under the control of personnel
involved with testing the specimen at all times; this control implies that the opportunity for specimen
tampering would be limited.
Interpretation: Reports will specifically indicate the presence or absence of cocaine and
benzoylecgonine. The presence of cocaine, or its major metabolite, benzoylecgonine, indicates use
within the past 4 days. Cocaine has a 6-hour half-life, so it will be present in urine for 1 day after last
use. Benzoylecgonine has a half-life of 12 hours, so it will be detected in urine up to 72 hours after last
use. There is no correlation between concentration and pharmacologic or toxic effects.
Reference Values:
Negative
Positives are reported with a quantitative GC-MS result.
Cutoff concentrations:
IMMUNOASSAY SCREEN
<150 ng/mL
COCAINE BY GC-MS
<50 ng/mL
BENZOYLECGONINE BY GC-MS
<50 ng/mL
Clinical References: 1. Baselt RC, Cravey RH: Disposition of Toxic Drugs and Chemicals in
Man. Third edition. Chicago, Year Book Medical Publishers, 1989 2. Langman LJ, Bechtel L, Holstege
CP: Chapter 35. In Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Edited by CA
Burtis, ER Ashwood, DE Bruns. WB Saunders Company, 2011, pp 1109-1188
Reference Values:
Negative
Positives are reported with a quantitative GC-MS result.
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Cutoff concentrations:
COCAINE BY GC-MS
<50 ng/mL
BENZOYLECGONINE BY GC-MS
<50 ng/mL
Clinical References: 1. Baselt RC, Cravey RH: Disposition of Toxic Drugs and Chemicals in Man.
Third edition. Chicago, Year Book Medical Publishers, 1989 2. Langman LJ, Bechtel L, Holstege CP:
Chapter 35: Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Edited by CA Burtis, ER
Ashwood, DE Bruns. WB Saunders Company, 2011, pp 1109-1188
Reference Values:
Negative
Positives are reported with a quantitative LC-MS/MS result.
Cutoff concentrations
Cocaine by LC-MS/MS: 50 ng/g
Benzoylecgonine by LC-MS/MS: 50 ng/g
Cocaethylene by LC-MS/MS: 50 ng/g
m-Hydroxybenzoylecgonine by LC-MS/MS: 50 ng/g
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 562
Lakshmanan J, Morgan BL, Ross MG: Meconium passage in utero: mechanisms, consequences, and
management. Obstet Gynecol Surv 2005;60:45-56
Reference Values:
Negative
Clinical References: 1. Thompson GR: Pulmonary coccidioidomycosis. Semin Respir Crit Care
Med 2011;32(6):754-763 2. Ruddy BE, Mayer AP, Ko MG, et al: Coccidioidomycosis in African
Americans. Mayo Clin Proc 2011;86(1):63-69
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patients develop fever, cough, malaise, and anorexia; chest pain is often severe. Coccidioidomycosis
may disseminate beyond the lungs to involve multiple organs including the meninges. IgG antibody is
detected by the complement-fixation tests. Precipitating antibodies (IgM and IgG) are detected by
immunodiffusion. They are rarely found in cerebrospinal fluid; however, their presence is associated
with meningitis. Chronic coccidioidal pulmonary cavities are often accompanied by IgG and IgM
precipitating antibodies.
Interpretation: Complement Fixation (CF): Titers of > or =1:2 may suggest active disease; however,
titers may persist for months after infection has resolved. Increasing CF titers in serial specimens are
diagnostic of active disease. Immunodiffusion (ID): The presence of IgM antibody may be detectable
within 2 weeks after the onset of symptoms; however, antibody may be detected longer than 6 months
after infection. The presence of IgG antibody parallels the CF antibody and may suggest an active or a
recent asymptomatic infection with Coccidioides immitis; however, antibody may persist after the
infection has resolved. An equivocal result (a band of nonidentity) cannot be interpreted as significant for
a specific diagnosis. However, this may be an indication that a patient should be followed serologically.
Over 90% of primary symptomatic cases will be detected by combined ID and CF testing.
Reference Values:
COMPLEMENT FIXATION
Negative
If positive, results are titered.
IMMUNODIFFUSION
Negative
Results are reported as positive, negative, or equivocal.
Useful For: Serologic testing for coccidioidomycosis should be considered when patients exhibit
symptoms of meningeal infection and have lived or traveled in areas where Coccidioides immitis is
endemic. Any history of exposure to the organism or travel cannot be overemphasized when
coccidioidomycosis serologic tests are being considered.
Interpretation: Complement Fixation (CF): IgG antibody is detected by CF testing. Any CF titer in
cerebrospinal fluid (CSF) should be considered significant. A positive complement fixation test in
unconcentrated CSF is diagnostic of meningitis. Immunodiffusion (ID): IgM and IgG precipitins are
rarely found in CSF. However, when present, they are diagnostic of meningitis (100% specific). Since the
ID test is 100% specific, it is helpful in interpreting CF results. Early primary antibody (IgM) found in
coccidioidomycosis can be detected by the IgM-specific ID test. IgM precipitins may be detectable within
1 to 4 weeks after the onset of symptoms. The presence of IgG antibody parallels the CF antibody and
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indicates an active or a recent asymptomatic infection with Coccidioides immitis. Both IgG and IgM
antibodies are rarely detected 6 months after infection. However, in some patients having disseminated
infection, both IgG and IgM antibodies may be present for several years. IgM and IgG precipitins are not
prognostic. An equivocal result (a band of nonidentity) cannot be interpreted as significant for a specific
diagnosis. However, this may be an indication that a patient should be followed serologically. The
sensitivity of serologic testing (CF and ID combined) for coccidioidomycosis is >90% or primary
symptomatic cases.
Reference Values:
COMPLEMENT FIXATION
Negative
If positive, results are titered.
IMMUNODIFFUSION
Negative
Results are reported as positive, negative, or equivocal.
Useful For: Rapid detection of Coccidioides DNA, preferred method An aid in diagnosing
coccidioidomycosis
Reference Values:
Not applicable
Clinical References: 1. Chiller TM, Galgiani JN, Stevens DA: Coccidioidomycosis. Infect Dis
Clin North Am 2003;17:41-57 2. Feldman BS, Snyder LS: Primary pulmonary coccidioidomycosis.
Semin Respir Infect 2001;16:231-237 3. Padhye AA, Smith G, Standard PG, et al: Comparative
evaluation of chemiluminescent DNA probe assays and exoantigen tests for rapid identification of
Blastomyces dermatitis and Coccidioides immitis. J Clin Microbiol 1994;32:867-870 4. Inoue T,
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Nabeshima K, Kataoka H, Koono M: Feasibility of archival non-buffered formalin-fixed and
paraffin-embedded tissues for PCR amplification: an analysis of resected gastric carcinoma. Pathol Int
1996;46:997-1004 5. Binnicker MH, Popa AS, Catania J, et al: Meningeal coccidioidomycosis
diagnosed by real-time polymerase chain reaction analysis of cerebrospinal fluid. Mycopathologia
2011;171:285-289 6. Vucicevic D, Blair JE, Binnicker MJ, et al: The utility of Coccidioides polymerase
chain reaction testing in the clinical setting. Mycopathologia 2010;170:345-351
Reference Values:
Not applicable
Clinical References: 1. Chiller TM, Galgiani JN, Stevens DA: Coccidioidomycosis. Infect Dis Clin
North Am 2003;17:41-57 2. Feldman BS, Snyder LS: Primary pulmonary coccidioidomycosis. Semin
Respir Infect 2001;16:231-237 3. Padhye AA, Smith G, Standard PG, et al: Comparative evaluation of
chemiluminescent DNA probe assays and exoantigen tests for rapid identification of Blastomyces
dermatitis and Coccidioides immitis. J Clin Microbiol 1994;32:867-870 4. Inoue T, Nabeshima K,
Kataoka H, Koono M: Feasibility of archival non-buffered formalin-fixed and paraffin-embedded tissues
for PCR amplification: an analysis of resected gastric carcinoma. Pathol Int 1996;46:997-1004
Reference Values:
<0.35 kU/L
Reference Values:
<0.35 kU/L
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 567
immune response to allergen(s) that may be associated with allergic disease. The allergens chosen for
testing often depend upon the age of the patient, history of allergen exposure, season of the year, and
clinical manifestations. In individuals predisposed to develop allergic disease(s), the sequence of
sensitization and clinical manifestations proceed as follows: eczema and respiratory disease (rhinitis and
bronchospasm) in infants and children less than 5 years due to food sensitivity (milk, egg, soy, and
wheat proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical utility
of food-specific IgG tests has not been established. These tests can be used in special clinical situations to
select foods for evaluation by diet elimination and challenge in patients who have food-related
complaints. It should be recognized that the presence of food-specific IgG alone cannot be taken as
evidence of food allergy and only indicates immunologic sensitization by the food allergen in question.
This test should only be ordered by physicians who recognize the limitations of the test.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 568
immunoglobulin E (IgE)-sensitized effector cells (mast cells and basophils) when cell-bound IgE
antibodies interact with allergen. In vitro serum testing for IgE antibodies provides an indication of the
immune response to allergen(s) that may be associated with allergic disease. The allergens chosen for
testing often depend upon the age of the patient, history of allergen exposure, season of the year, and
clinical manifestations. In individuals predisposed to develop allergic disease(s), the sequence of
sensitization and clinical manifestations proceed as follows: eczema and respiratory disease (rhinitis and
bronchospasm) in infants and children less than 5 years due to food sensitivity (milk, egg, soy, and wheat
proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 569
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: Diagnosis of coenzyme Q10 (CoQ10) deficiency in mitochondrial disorders Monitoring
patients receiving statin therapy Monitoring CoQ10 status during treatment of various degenerative
conditions including Parkinson and Alzheimer disease
Interpretation: Abnormal results are reported with a detailed interpretation including an overview of
the results and their significance, a correlation to available clinical information provided with the
specimen, differential diagnosis, and recommendations for additional testing when indicated and
available, and a phone number to reach a laboratory director in case the referring physician has additional
questions.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 570
Reference Values:
CoQ10 REDUCED
<18 years: 320-1,376 mcg/L
> or =18 years: 415-1,480 mcg/L
TOTAL CoQ10
<18 years: 320-1,558 mcg/L
> or =18 years: 433-1,532 mcg/L
% REDUCED CoQ10
<18 years: 93-100%
> or =18 years: 92-98%
Miles MV, Horn PS, Tang PH, et al: Age-related changes in plasma coenzyme Q10 concentrations and
redox state in apparently healthy children and adults. Clin Chim Acta 2004;34:139-144
Clinical References: 1. Littarru GP, Tiano L: Clinical aspects of coenzyme Q10: An update.
Nutrition 2010;26:250-254 2. Miles MV, Horn PS, Morrison JA, et al: Plasma coenzyme Q10 reference
intervals, but not redox status, are affected by gender and race in self-reported healthy adults. Clin Chim
Acta 2003 June;332(1-2):123-132 3. Quinzii CA, Hirano M: Coenzyme Q and mitochondrial disease.
Dev Disabil Res Rev 2010 June;16(2):183-188 4. Steele PE, Tang PH, DeGrauw AJ, Miles MV:
Clinical laboratory monitoring of coenzyme Q10 use in neurologic and muscular diseases. Am J Clin
Pathol 2004 June;121:S113-S120 5. Quinzii CM, Hirano M, DiMauro S: CoQ10 deficiency diseases in
adults. Mitochondrion 2007 June;7(Suppl): S122-S126 6. Banach M, Serban C, Ursoniu S, et al; Lipid
and Blood Pressure Meta-analysis Collaboration (LBPMC) Group. Statin therapy and plasma coenzyme
Q10 concentrations--A systematic review and meta-analysis of placebo-controlled trials. Pharmacol Res
2015 Sep;99:329-336
Useful For: Diagnosis of coenzyme Q10 (CoQ10) deficiency in mitochondrial disorders Monitoring
patients receiving statin therapy Monitoring CoQ10 status during treatment of various degenerative
conditions including Parkinson and Alzheimer disease This test can be used for hemolyzed specimens to
provide accurate quantitation of total coenzyme Q10.
Interpretation: Abnormal results are reported with a detailed interpretation including an overview of
the results and their significance, a correlation to available clinical information provided with the
specimen, differential diagnosis, and recommendations for additional testing when indicated and
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 571
available.
Reference Values:
TOTAL CoQ10
<18 years: 320-1,558 mcg/L
> or =18 years: 433-1,532 mcg/L
Miles MV, Horn PS, Tang PH, et al: Age-related changes in plasma coenzyme Q10 concentrations and
redox state in apparently healthy children and adults. Clin Chim Acta 2004;34:139-144
Clinical References: 1. Littarru GP, Tiano L: Clinical aspects of coenzyme Q10: An update.
Nutrition 2010;26:250-254 2. Miles MV, Horn PS, Morrison JA, et al: Plasma coenzyme Q10 reference
intervals, but not redox status, are affected by gender and race in self-reported healthy adults. Clin Chim
Acta 2003 June;332(1-2):123-132 3. Quinzii CA, Hirano M: Coenzyme Q and mitochondrial disease.
Deve Disabil Res Rev 2010 June;16(2):183-188 4. Steele PE, Tang PH, DeGrauw AJ, Miles MV: Clinical
laboratory monitoring of coenzyme Q10 use in neurologic and muscular diseases. Am J Clin Pathol 2004
June;121:S113-S120 5. Quinzii CM, Hirano M, DiMauro S: CoQ10 deficiency diseases in adults.
Mitochondrion 2007 June;7(Suppl): S122-S126 6. Banach M, Serban C, Ursoniu S, et al; Lipid and Blood
Pressure Meta-analysis Collaboration (LBPMC) Group. Statin therapy and plasma coenzyme Q10
concentrations--A systematic review and meta-analysis of placebo-controlled trials. Pharmacol Res 2015
Sep;99:329-336
Reference Values:
<0.35 kU/L
Useful For: Detection of cold agglutinins in patients with suspected cold agglutinin disease
Interpretation: Patients with cold agglutinin syndrome usually exhibit a titer value above 1:512, with
rare cases reportedly as low as 1:64. Normal individuals often have low levels of cold agglutinins. The
test is not a direct measure of clinical significance and must be used in conjunction with other in vitro and
in vivo parameters.
Reference Values:
<1:64
Clinical References: 1. Petz LD, Garratty G: Acquired Immune Hemolytic Anemias. New York,
Churchill Livingstone, 1980 2. Farratty G, Petz LD, Hoops JK: The correlation of cold agglutinin
titrations in saline and albumin with haemolytic anaemia. Br J Haematol 1977;35:587-595
Useful For: Marker of the basal lamina of capillaries and basement membranes in all organs
Interpretation: This test includes only technical performance of the stain (no pathologist
interpretation is performed). If diagnostic consultation by a pathologist is required order 70012 /
Pathology Consultation. The positive and negative controls are verified as showing appropriate
immunoreactivity. If a control tissue is not included on the slide, a scanned image of the relevant quality
control tissue is available upon request. Please contact 1-855-516-8404. Interpretation of this test should
be performed in the context of the patient's clinical history and other diagnostic tests by a qualified
pathologist.
Clinical References: 1. Abreu-Velez AM, Howard MS: Collagen IV in normal skin and in
pathological processes. N Am J Med Sci. 2012;4(1):1-8 2. Agarwal P, Ballabh R: Expression of type IV
collagen in different histological grades of oral squamous cell carcinoma: An Immunohistochemical
Study. Journal of Cancer Research and Therapeutics 2013;9(2):272-275 3. David L, Nesland JM, Holm
R, Sobrinho-Simoes M: Expression of laminin, collagen IV, fibronectin, and type IV collagenase in
gastric carcinoma. An Immunohistochemical Study of 87 Patients. Cancer 1994;73(3):518-527
Reference Values:
Negative: <20 EU/mL
Borderline/Equivocal: 20-25 EU/mL
Positive: >25 EU/mL
Useful For: This testing is recommended in cases of chorea, vision loss, cranial neuropathy and
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 573
myelopathy. It is recommended that PAVAL - Paraneoplastic Autoantibody Evaluation be ordered in
conjunction with this test if not previously performed. Western blot analysis is indicated when
interfering nonorgan-specific or coexisting neuron-specific autoantibodies in serum or spinal fluid
preclude unambiguous detection of CRMP-5-IgG, by indirect immunofluorescence assay, or when the
immunofluorescence assay is negative in a patient whose neurological presentation suggests a
CRMP-5-IgG-related syndrome.
Interpretation: A positive result confirms that a patient's subacute neurological disorder has an
autoimmune basis, and is likely to be associated with a small-cell lung carcinoma (SCLC) or thymoma,
which may be occult.(1,2) A positive result has a predictive value of 90% for neoplasm (77% SCLC, 6%
thymoma [1]). Seropositivity is found in approximately 3% of patients who have SCLC with limited
metastasis without evidence of neurological autoimmunity.(6) Clinical-serological correlations have not
yet been established for children. Western blot analysis is indicated when interfering nonorgan-specific or
coexisting neuron-specific autoantibodies in serum or spinal fluid preclude unambiguous detection of
CRMP-5-IgG by indirect immunofluorescence assay, or when the immunofluorescence assay is negative
in a patient whose neurological presentation suggests a CRMP-5-IgG-related syndrome.
Reference Values:
Negative (reported as positive or negative)
Clinical References: 1. Yu Z, Kryzer TJ, Griesmann GE, et al: CRMP-5 neuronal autoantibody:
marker of lung cancer and thymoma-related autoimmunity. Ann Neurol 2001 February;49(2):146-154 2.
Vernino S, Tuite P, Adler CH, et al: Paraneoplastic chorea associated with CRMP-5 neuronal antibody
and lung carcinoma. Ann Neurol 2002 May;51(5):625-630 3. Vernino S, Lennon VA: Autoantibody
profiles and neurological correlations of thymoma. Clin Cancer Res 2004;10(21):7270-7275 4. Galanis E,
Frytak S, Rowland KM Jr, et al: Neuronal autoantibody titers in the course of small cell lung carcinoma
and platinum associated neuropathy. Cancer Immunol Immunother 1999 May-June;48(2-3):85
Useful For: This testing is recommended in cases of chorea, vision loss, cranial neuropathy and
myelopathy. It is recommended that PAVAL - Paraneoplastic Autoantibody Evaluation be ordered in
conjunction with this test if not previously performed. Western blot analysis is indicated when interfering
nonorgan-specific or coexisting neuron-specific autoantibodies in serum or spinal fluid preclude
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 574
unambiguous detection of CRMP-5-IgG, by indirect immunofluorescence assay, or when the
immunofluorescence assay is negative in a patient whose neurological presentation suggests a
CRMP-5-IgG-related syndrome.
Interpretation: A positive result confirms that a patient's subacute neurological disorder has an
autoimmune basis and is likely to be associated with a small-cell lung carcinoma (SCLC) or thymoma,
which may be occult.(1,2) A positive result has a predictive value of 90% for neoplasm (77% SCLC,
6% thymoma[1]). Seropositivity is found in approximately 3% of patients who have SCLC with limited
metastasis without evidence of neurological autoimmunity.(6) Clinical-serological correlations have not
yet been established for children.
Reference Values:
Negative (reported as positive or negative)
Clinical References: 1. Yu Z, Kryzer TJ, Griesmann GE, et al: CRMP-5 neuronal autoantibody:
marker of lung cancer and thymoma-related autoimmunity. Ann Neurol 2001 February;49(2):146-154
2. Vernino S, Tuite P, Adler CH, et al: Paraneoplastic chorea associated with CRMP-5 neuronal
antibody and lung carcinoma. Ann Neurol 2002 May;51(5):625-630 3. Vernino S, Lennon VA:
Autoantibody profiles and neurological correlations of thymoma. Clin Cancer Res
2004;10(21):7270-7275 4. Galanis E, Frytak S, Rowland KM Jr, et al: Neuronal autoantibody titers in
the course of small cell lung carcinoma and platinum associated neuropathy. Cancer Immunol
Immunother 1999 May-June;48(2-3):85-90
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 575
5 50.0-99.9 Strongly positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: Screening for common variable immunodeficiency (CVID) Identifying defects in TACI
and BAFF-R in patients presenting with clinical symptoms and other laboratory features consistent with
CVID Evaluating B cell immune competence by assessing expression of BAFF-R and TACI proteins
Useful for assessing BAFF-R and TACI protein expression and frequency of B cells bearing these
receptors. TNFRSF13C (BAFF-R) and TNFRSF13B (TACI) gene mutations have been described in a
small subset of patients with humoral immunodeficiencies classified as CVID. The majority of
TNFRSF13B mutations preserve TACI protein expression and require genetic testing to identify
pathogenic or potentially pathogenic mutations/variants.
Interpretation: BAFF-R is normally expressed on over 95% of B cells, while TACI is expressed on
a smaller subset of B cells (3%-70%) and some activated T cells. Expression on B cells increases with B
cell activation. The lack of TACI or BAFF-R surface expression on B cells is suggestive of a potential
common variable immunodeficiency (CVID)-associated defect, if other features of CVID are present.
The majority of TACI mutations (>95%) preserve protein expression but abrogate protein function,
hence the only way to conclusively establish a TACI mutational defect is to perform genetic testing
(TACIF / Transmembrane Activator and CAML Interactor [TACI] Gene, Full Gene Analysis).
Reference Values:
%CD19+TACI+: >3.4%
%CD19+BAFF-R+: >90.2%
Reference values apply to all ages.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 577
Clinical References: 1. Warnatz K, Denz A, Drager R, et al: Severe deficiency of switched memory
B cells (CD27+ IgM-IgD-) in subgroups of patients with common variable immunodeficiency: a new
approach to classify a heterogeneous disease. Blood 2002;99:1544-1551 2. Grimbacher B, Hutloff A,
Schlesier M, et al: Homozygous loss of ICOS is associated with adult-onset common variable
immunodeficiency. Nat Immunol 2003;4(3):261-268 3. Salzer U, Chapel HM, Webster AD, et al:
Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in
humans. Nat Genet 2005;37(8):820-828 4. van Zelm M, Reisli I, van der Burg M, et al: An
antibody-deficiency syndrome due to mutations in the CD19 gene. N Engl J Med 2006;354:1901-1912 5.
Warnatz K, Salzer U, Gutenberger S, et al: Finally found: human BAFF-R deficiency causes
hypogammaglobulinemia. Clin Immunol 2005;115(Suppl 1):820
Clinical References: 1. Fedson SE, Daniel SS, Husain AN: Immunohistochemistry staining of C4d
to diagnose antibody-mediated rejection in cardiac transplantation. The Journal of Heart and Lung
Transplantation 2008;27(4):372-379 2. Magro CM, Dyrsen ME: The use of C3d and C4d
immunohistochemistry on formalin-fixed tissue as a diagnostic adjunct in the assessment of inflammatory
skin disease. J AM Acad Dermatol 2008;59(5):822-833 3. Roden AC, Scott JP, Jenkins SM, Aubry MC:
C4d by immunofluorescence and immunohistochemistry in routine lung allograft biopsies. The Journal of
Heart and Lung Transplantation 2013;32(45):519-520
Useful For: Assessment of an undetectable total complement (CH50) level Diagnosing congenital C1
(first component of complement) deficiency Diagnosing acquired deficiency of C1 inhibitor
Interpretation: An undetectable C1q in the presence of an absent total complement (CH50) and
normal C2, C3, and C4 suggests a congenital C1 (first component of complement) deficiency. A low C1q
in combination with a low C1 inhibitor and low C4 suggests an acquired C1 inhibitor deficiency.
Reference Values:
12-22 mg/dL
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Clinical References: 1. Frank MM: Complement in the pathophysiology of human disease. N
Engl J Med 1987 June 11;316(24):1525-1530 2. Frank MM: Complement deficiencies. Pediatr Clin
North Am 2000 December;47(6):1339-1354 3. Frigas E: Angioedema with acquired deficiency of the
C1 inhibitor: a constellation of syndromes. Mayo Clin Proc 1989 October;64(10):1269-1275
Useful For: Assessing disease activity in systemic lupus erythematosus (SLE) Investigating an
undetectable total complement (CH50) level
Interpretation: A decrease in C3 levels to the abnormal range is consistent with disease activation in
systemic lupus erythematosus (SLE).
Reference Values:
75-175 mg/dL
Clinical References: 1. Ross SC, Densen P: Complement deficiency states and infection:
epidemiology, pathogenesis, and consequences of neisserial and other infections in an immune
deficiency. Medicine 1984;63:243-273 2. Frank MM: Complement in the pathophysiology of human
disease. N Engl J Med 1987;316:1525-1530
Reference Values:
14-40 mg/dL
Clinical References: 1. Ross SC, Densen P: Complement deficiency states and infection:
epidemiology, pathogenesis, and consequences of neisserial and other infections in an immune
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 579
deficiency. Medicine 1984;63:243-273 2. Frank MM: Complement in the pathophysiology of human
disease. N Engl J Med 1987;316:1525-1530 3. Tiffany TO: Fluorometry, nephelometry, and
turbidimetry. In Textbook of Clinical Chemistry. Edited by NW Tietz. Philadelphia, WB Saunders
Company, 1986, pp 79-97
Useful For: Investigation of suspected alternative pathway complement deficiency, atypical hemolytic
uremic syndrome, C3 glomerulonephritis, dense-deposit disease
Interpretation: Absent complement alternate pathway (AH50) in the presence of a normal total
hemolytic complement (CH50) suggests an alternate pathway component deficiency. Normal AH50 with
absent CH50 suggests an early (C1, C2, C4) classic pathway deficiency. Absent AH50 and CH50
suggests a late (C3, C5, C6, C7, C8, C9) component deficiency or complement consumption. Absent
AH50 and CH50 in the presence of a normal C3 and C4 suggests a late (C5, C6, C7, C8, C9) component
deficiency.
Reference Values:
> or =46% normal
Clinical References: 1. Frank MM: Medical intelligence current concepts: complement in the
pathophysiology of human disease. N Engl J Med 1987;316:1525-1530 2. Thurman JM, Holers VM:
Brief reviews: the central role of the alternative complement pathway in human disease. J Immunol
2006;176:1305-1310 3. Frank MM: Complement deficiencies. Pediatr Clin North Am
2000;47(6):1339-54
Useful For: Detection of individuals with an ongoing immune process First-order screening test for
congenital complement deficiencies
Interpretation: Low levels of total complement (total hemolytic complement CH50) may occur
during infections, disease exacerbation in patients with systemic lupus erythematosus, and in patients
with immune complex diseases such as glomerulonephritis. Undetectable levels suggest the possibility
of a complement component deficiency. Individual complement component assays are useful to identify
the specific deficiency.
Reference Values:
> or =16 years: 30-75 U/mL
Reference values have not been established for patients that are <16 years of age.
Clinical References: 1. Ross SC, Densen P: Complement deficiency states and infection:
epidemiology, pathogenesis and consequences of neisserial and other infections in an immune
deficiency. Medicine 1984;63:243-273 2. Frank MM: Complement in the pathophysiology of human
disease. N Engl J Med 1987;316:1525-1530 3. Yamamoto S, Kubotsu K, Kida M, et al: Automated
homogeneous liposome-based assay system for total complement activity. Clin Chem 1995;41:586-590
Useful For: Providing a comprehensive genetic evaluation for patients with a personal or family
history suggestive of an the hereditary cardiomyopathy Establishing a diagnosis of a hereditary
cardiomyopathy and, in some cases, allowing for appropriate management and surveillance for disease
features based on the gene involved Identification of a pathogenic variant within a gene known to be
associated with disease that allows for predictive testing of at-risk family members
Interpretation: Evaluation and categorization of variants is performed using the most recent
published American College of Medical Genetics and Genomics (ACMG) recommendations as a
guideline. Variants are classified based on known, predicted, or possible pathogenicity and reported
with interpretive comments detailing their potential or known significance. Multiple in silico evaluation
tools may be used to assist in the interpretation of these results. The accuracy of predictions made by in
silico evaluation tools is highly dependent upon the data available for a given gene, and predictions
made by these tools may change over time. Results from in silico evaluation tools should be interpreted
with caution and professional clinical judgment.
Reference Values:
An interpretive report will be provided.
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CAH2T Congenital Adrenal Hyperplasia (CAH) Newborn Screen, Blood
42202 Spot
Clinical Information: Congenital adrenal hyperplasia (CAH) is a group of disorders caused by
inherited defects in steroid biosynthesis, most commonly, 21-hydroxylase deficiency (approximately 90%
of cases) and 11-beta hydroxylase deficiency (approximately 5% of cases). The overall incidence of CAH
due to 21-hydroxylase deficiency is approximately 1 in 15,000 live births. Individuals with CAH may
present with life-threatening salt-wasting crises in the newborn period and incorrect gender assignment of
virilized females as a result of reduced glucocorticoids and mineralocorticoids and elevated
17-hydroxyprogesterone (17-OHP) and androgens. Hormone replacement therapy, when initiated early,
results in a significant reduction in morbidity and mortality. Therefore, newborn screening for CAH is
desirable and has been implemented in all 50 states. Immunoassays are typically used to quantify 17-OHP
as a marker for CAH. However, these immunoassays are hampered by cross-reactivity of the antibodies
with other steroids, yielding a high rate of false-positive results. Tandem mass spectrometry (MS/MS)
allows for the simultaneous specific determination of 17-OHP and other steroids, such as
androstenedione, cortisol, 11-deoxycortisol, and 21-deoxycortisol. Application of this technology to the
determination of steroids in newborn screening blood spots significantly enhances the correct
identification of patients with CAH and reduces the number of false-positive screening results when
implemented as a second-tier analysis performed prior to reporting of initial newborn screen results.
Useful For: Second-tier testing of newborns with abnormal screening result for congenital adrenal
hyperplasia
Interpretation: Findings of a 17-hydroxyprogesterone (17-OHP) value greater than 15.0 ng/mL and a
high (17-OHP + androstenedione)/cortisol ratio (> or =1) are supportive of the initial abnormal newborn
screening result. Findings of an 11-deoxycortisol value greater than 15.0 ng/mL or 21-deoxycortisol
greater than 4.0 ng/mL with elevated 17-OHP further support the abnormal newborn screening result and
increase the diagnostic specificity. Clinical and laboratory follow-up is strongly recommended.
Reference Values:
17-HYDROXYPROGESTERONE
<15.1 ng/mL
ANDROSTENEDIONE
<3.1 ng/mL
CORTISOL
Not applicable
11-DEOXYCORTISOL
<15.1 ng/mL
21-DEOXYCORTISOL
<4.1 ng/mL
11-DEOXYCORTISOL/CORTISOL RATIO
Not applicable
Clinical References: 1. Antal Z, Zhou P: Congenital adrenal hyperplasia: diagnosis, evaluation and
management. Pediatr Rev 2009 Jul;30(7):e49-57 2. Minutti CZ, Lacey JM, Magera MJ, et al: Steroid
profiling by tandem mass spectrometry improves the positive predictive value of newborn screening for
congenital adrenal hyperplasia. J Clin Endo Met 2004;89:3687-3693 3. Turcu AF, Auchus RJ: The next
150 years of congenital adrenal hyperplasia. J Steroid Biochem Mol Biol 2015 Sep;153:63-714 4. Witchel
SF, Azziz R: Congenital adrenal hyperplasia. Pediatri Adolesc Gynecol 2011;24:116-126
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CAH21 Congenital Adrenal Hyperplasia (CAH) Profile for
87815 21-Hydroxylase Deficiency
Clinical Information: The cause of congenital adrenal hyperplasia (CAH) is an inherited genetic
defect that results in decreased formation of 1 of the many enzymes that are involved in the production
of cortisol. The enzyme defect results in reduced glucocorticoids and mineralocorticoids, and elevated
17-hydroxyprogesterone (OHPG) and androgens. The resulting hormone imbalances can lead to
life-threatening, salt-wasting crises in the newborn period and incorrect gender assignment of virilized
females. Adult-onset CAH may result in hirsutism or infertility in females. The adrenal glands, ovaries,
testes, and placenta produce OHPG. It is hydroxylated at the 11 and 21 positions to produce cortisol.
Deficiency of either 11- or 21-hydroxylase results in decreased cortisol synthesis, and the feedback
inhibition of adrenocorticotropic hormone (ACTH) secretion is lost. Consequently, increased pituitary
release of ACTH increases production of OHPG. In contrast, if 17-alpha-hydroxylase (which allows
formation of OHPG from progesterone) or 3-beta-ol-dehydrogenase (which allows formation of
17-hydroxyprogesterone formation from 17-hydroxypregnenolone) are deficient, OHPG levels are low
with possible increase in progesterone or pregnenolone, respectively. Most (90%) cases of CAH are due
to mutations in the 21-hydroxylase gene (CYP21A2). CAH due to 21-hydroxylase deficiency is
diagnosed by confirming elevations of OHPG and androstenedione with decreased cortisol. By contrast,
in 2 less common forms of CAH, due to 17-hydroxylase or 11-hydroxylase deficiency, OHPG and
androstenedione levels are not significantly elevated and measurement of progesterone (PGSN /
Progesterone, Serum) and deoxycorticosterone (DCRN / 11-Deoxycorticosterone, Serum), respectively,
are necessary for diagnosis. OHPG is bound to both transcortin and albumin, and total OHPG is
measured in this assay. OHPG is converted to pregnanetriol, which is conjugated and excreted in the
urine. In all instances, more specific tests than pregnanetriol measurement are available to diagnose
disorders of steroid metabolism. The CAH profile allows the simultaneous determination of OHPG,
androstenedione, and cortisol. These steroids can also be ordered individually (OHPG /
17-Hydroxyprogesterone, Serum; ANST / Androstenedione, Serum; CINP / Cortisol, Serum,
LC-MS/MS).
Useful For: Preferred screening test for congenital adrenal hyperplasia (CAH) that is caused by
21-hydroxylase deficiency Part of a battery of tests to evaluate females with hirsutism or infertility,
which can result from adult-onset CAH
Interpretation: Diagnosis and differential diagnosis of congenital adrenal hyperplasia (CAH) always
requires the measurement of several steroids. Patients with CAH due to 21-hydroxylase gene
(CYP21A2) mutations usually have very high levels of androstenedione, often 5- to 10-fold elevations.
17-Hydroxyprogesterone (OHPG) levels are usually even higher, while cortisol levels are low or
undetectable. All 3 analytes should be tested. In the much less common CYP11A mutation,
androstenedione levels are elevated to a similar extent as in CYP21A2 mutation, and cortisol is also
low, but OHPG is only mildly, if at all, elevated. Also less common is 3 beta-hydroxysteroid
dehydrogenase type 2 (3 beta HSD-2) deficiency, characterized by low cortisol and substantial
elevations in dehydroepiandrosterone sulfate (DHEA-S) and 17-alpha-hydroxypregnenolone, while
androstenedione is either low, normal, or rarely, very mildly elevated (as a consequence of peripheral
tissue androstenedione production by 3 beta HSD-1). In the very rare steroidogenic acute regulatory
protein deficiency, all steroid hormone levels are low and cholesterol is elevated. In the also very rare
17-alpha-hydroxylase deficiency, androstenedione, all other androgen-precursors
(17-alpha-hydroxypregnenolone, OHPG, DHEA-S), androgens (testosterone, estrone, estradiol), and
cortisol are low, while production of mineral corticoid and its precursors, in particular progesterone,
11-deoxycorticosterone, corticosterone, and 18-hydroxycorticosterone, are increased. The goal of CAH
treatment is normalization of cortisol levels and, ideally, also of sex-steroid levels. OHPG is measured
to guide treatment, but this test correlates only modestly with androgen levels. Therefore,
androstenedione and testosterone should also be measured and used to guide treatment modifications.
Normal prepubertal levels may be difficult to achieve, but if testosterone levels are within the reference
range, androstenedione levels up to 100 ng/dL are usually regarded as acceptable.
Reference Values:
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Tanner Stages Age (Years) Reference Range (ng/dL)
Stage I (prepubertal)
Stage I (prepubertal)
Order MPCT / Muscle Pathology Consultation or MBCT / Muscle Biopsy Consultation, Outside Slides
and/or Paraffin Blocks. The consultant will determine the need for special stains.
Useful For: Evaluation of patients with signs and symptoms compatible with connective tissue
diseases
Interpretation: Interpretive comments are provided. See individual unit codes for additional
information.
Reference Values:
ANTINUCLEAR ANTIBODIES (ANA)
< or =1.0 U (negative)
1.1-2.9 U (weakly positive)
3.0-5.9 U (positive)
> or =6.0 U (strongly positive)
Reference values apply to all ages.
Clinical References: 1. Kavanaugh A, Tomar R, Reveille J, et al: Guidelines for clinical use of the
antinuclear antibody test and tests for specific autoantibodies to nuclear antigens. Arch Pathol Lab Med
2000;124:71-81 2. van Boekel MA, Vossenaar ER, van den Hoogen FH, van Venrooij WJ:
Autoantibody systems in rheumatoid arthritis: specificity, sensitivity and diagnostic value. Arthritis Res
2002;4:87-93 3. Tomar R, Homburger H: Assessment of immunoglobulins and antibodies. In Clinical
Immunology Principles and Practice. Second edition. Edited by R Rich, T Fleisher, W Shearer, et al. St.
Louis, Mosby-Year Book, 2001, pp 120.1-120.14 4. Homburger HA: Cascade testing for autoantibodies
in connective tissue diseases. Mayo Clin Proc 1995;70:183-184
Reference Values:
0-17 years: not established
> or =18 years: < or =60 mcg/24h
Clinical References: 1. Zorbas YG, Kakuris KK, Deogenov VA et al: Copper homeostasis during
hypokinesia in healthy subjects with higher and lower copper consumption. Trace Elements and
Electrolytes 2008;25:169-178 2. Lech T, Sadlik JK: Contribution to the data on copper concentration in
blood and urine in patients with Wilson's disease and in normal subjects. Biol Trace Elem Res 2007
July;118(1):16-20
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heterozygous carriers for WD occasionally have modestly elevated values, but rarely higher than 125
mcg/g of dry weight. In general, the liver copper content is higher than 250 mcg/g dried tissue in WD
patients. In patients with elevated levels of copper without supporting histology and other biochemical
test results, contamination during collection, handling, or processing should be considered. Fresh tissue
would be appropriate for copper measurement. Genetic test for WD (WDMS / Wilson Disease Mutation
Screen, ATP7B DNA Sequencing) is available at Mayo Clinic.
Reference Values:
10-35 mcg/g dry weight
Clinical References: 1. Korman J, Volenberg I, Balko J, et al: Screening for Wilson disease in
acute liver failure: a comparison of currently available diagnostic tests. Hepatology 2008
Oct;48(4):1167-1174 2. Roberts EA, Schlisky ML: Diagnosis and Treatment of Wilson Disease:
AASLD Practice Guidelines. Hepatology 2008;47:2089-2111 3. de Bie P, Muller P, Wijmenga C,
Klomp LW: Molecular pathogenesis of Wilson and Menkes disease: correlation of mutations with
molecular defects and disease phenotypes. J Med Genet 2007 November;44(11):673-688 4. Merle U,
Schaefer M, Ferenci P, Stremmel W: Clinical presentation, diagnosis and long-term outcome of
Wilson's disease: a cohort study. Gut 2007;56:115-120
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acute Wilson disease. Other disorders associated with decreased serum copper concentrations include
malnutrition, hypoproteinemia, malabsorption, nephrotic syndrome, Menkes disease, copper toxicity,
and megadosing of zinc-containing vitamins (zinc interferes with normal copper absorption from the
gastrointestinal tract). Hypercupremia is found in primary biliary cirrhosis, primary sclerosing
cholangitis, hemochromatosis, malignant diseases (including leukemia), thyrotoxicosis, and various
infections. Serum copper concentrations are also elevated in patients taking contraceptives or estrogens
and during pregnancy. Since the gastrointestinal (GI) tract effectively excludes excess copper, it is the
GI tract that is most affected by copper ingestion. Increased serum concentration does not, by itself,
indicate copper toxicity.
Useful For: Diagnosis of: -Wilson disease -Primary biliary cirrhosis -Primary sclerosing cholangitis
Interpretation: Serum copper below the normal range is associated with Wilson disease, as well as a
variety of other clinical situations (see Clinical Information). Excess use of denture cream containing zinc
can cause hypocupremia. Serum concentrations above the normal range are seen in primary biliary
cirrhosis and primary sclerosing cholangitis, as well as a variety of other clinical situations (see Clinical
Information).
Reference Values:
0-2 months: 0.40-1.40 mcg/mL
3-6 months: 0.40-1.60 mcg/mL
7-9 months: 0.40-1.70 mcg/mL
10-12 months: 0.80-1.70 mcg/mL
13 months-10 years: 0.80-1.80 mcg/mL
> or =11 years: 0.75-1.45 mcg/mL
Clinical References: 1. McCullough AJ, Fleming CR, Thistle JL, et al: Diagnosis of Wilson's
disease presenting as fulminant hepatic failure. Gastroenterology 1983;84:161-167 2. Wiesner RH,
LaRusso NF, Ludwig J, Dickson ER: Comparison of the clinicopathologic features of primary sclerosing
cholangitis and primary biliary cirrhosis. Gastroenterology 1985;88:108-114 3. Spain RI, Leist TP, De
Sousa EA: When metals compete: a case of copper-deficiency myeloneuropathy and anemia. Nat Clin
Pract Neurol 2009 Feb;5(2):106-111 4. Kale, SG, Holmes CS, Goldstein DS, et al: Neonatal Diagnosis
and Treatment of Menkes Disease. N Engl J Med 2008 Feb 7;358(6):605-614 5. Nations SP, Boyer PJ,
Love LA, et al: Denture cream: An unusual source of excess zinc, leading to hypocupremia and
neurologic disease. Neurology 2008;71;639-643
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inflammation. During the recovery phase, urine copper is usually below normal, reflecting the expected
physiologic response to replace the copper that was depleted during inflammation.
Reference Values:
0-17 years: not established
Male > or =18 years: 9-43 mcg/g creatinine
Female > or =18 years: 7-72 mcg/g creatinine
Clinical References: 1. Zorbas YG, Kakuris KK, Deogenov VA, Yerullis KB: Copper
homeostasis during hypokinesia in healthy subjects with higher and lower copper consumption. Trace
Elements and Electrolytes 2008;25:169-178 2. Lech T. Sadlik JK: Contribution to the data on copper
concentration in blood and urine in patients with Wilson's disease and in normal subjects. Biol Trace
Elem Res 2007 Jul;118(1):16-20
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
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FCORG Corn IgG
57526 Interpretation: mcg/mL of IgG Lower Limit of Quantitation* 2.0 Upper Limit of Quantitation** 200
Reference Values:
<2 mcg/mL
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical utility
of food-specific IgG tests has not been established. These tests can be used in special clinical situations to
select foods for evaluation by diet elimination and challenge in patients who have food-related
complaints. It should be recognized that the presence of food-specific IgG alone cannot be taken as
evidence of food allergy and only indicates immunologic sensitization by the food allergen in question.
This test should only be ordered by physicians who recognize the limitations of the test.
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical utility
of food-specific IgG4 tests has not been clearly established. These tests can be used in special clinical
situations to select foods for evaluation by diet elimination and challenge in patients who have food
related complaints, and to evaluate food allergic patients prior to food challenges. The presence of
food-specific IgG4 alone cannot be taken as evidence of food allergy and only indicated immunologic
sensitization to the food allergen in question.
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
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0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
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Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
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17-hydroxyprogesterone, aldosterone and cortisol measurements.
Useful For: Diagnosis of suspected 11-hydroxylase deficiency, including the differential diagnosis of
11 beta-hydroxylase 1 (CYP11B1) versus 11 beta-hydroxylase 2 (CYP11B2) deficiency, and the
diagnosis of glucocorticoid-responsive hyperaldosteronism Evaluating congenital adrenal hyperplasia
newborn screen-positive children, when elevations of 17-hydroxyprogesterone are only moderate,
thereby suggesting possible 11-hydroxylase deficiency
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Reference Values:
< or =18 years: 18-1,970 ng/dL
>18 years: 53-1,560 ng/dL
Useful For: Preferred screening test for Cushing syndrome Diagnosis of pseudo-hyperaldosteronism
due to excessive licorice consumption This test has limited usefulness in the evaluation of adrenal
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insufficiency
Interpretation: Most patients with Cushing syndrome have increased 24-hour urinary excretion of
cortisol. Further studies, including suppression or stimulation tests, measurement of serum
corticotrophin concentrations, and imaging are usually necessary to confirm the diagnosis and
determine the etiology. Values in the normal range may occur in patients with mild Cushing syndrome
or with periodic hormonogenesis. In these cases, continuing follow-up and repeat testing are necessary
to confirm the diagnosis. Patients with Cushing syndrome due to intake of synthetic glucocorticoids
should have suppressed cortisol. In these circumstances a synthetic glucocorticoid screen might be
ordered (SGSU / Synthetic Glucocorticoid Screen, Urine). Suppressed cortisol values may also be
observed in primary adrenal insufficiency and hypopituitarism. However, many normal individuals may
also exhibit a very low 24-hour urinary cortisol excretion with considerable overlap with the values
observed in pathological hypocorticalism. Therefore, without other tests, 24-hour urinary cortisol
measurements cannot be relied upon for the diagnosis of hypocorticalism.
Reference Values:
0-2 years: not established
3-8 years: 1.4-20 mcg/24 hours
9-12 years: 2.6-37 mcg/24 hours
13-17 years: 4.0-56 mcg/24 hours
> or =18 years: 3.5-45 mcg/24 hours
Use the factor below to convert from mcg/24 hours to nmol/24 hours:
Conversion factor
Cortisol: mcg/24 hours x 2.76=nmol/24 hours (molecular weight=362.5)
Clinical References: 1. Findling JW, Raff H: Diagnosis and differential diagnosis of Cushing's
syndrome. Endocrinol Metab Clin North Am 2001;30:729-747 2. Boscaro M, Barzon L, Fallo F, Sonino
N: Cushing's syndrome. Lancet 2001;357:783-791 3. Taylor RL, Machacek D, Singh RJ: Validation of
a high-throughput liquid chromatography-tandem mass spectrometry method for urinary cortisol and
cortisone. Clin Chem 2002;48:1511-1519
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methodology eliminates analytical interferences including carbamazepine (Tegretol) and synthetic
corticosteroids, which can affect immunoassay-based cortisol results.
Useful For: Investigating suspected hypercortisolism when a 24-hour collection is prohibitive (ie,
pediatric patients)
Interpretation: Most patients with Cushing syndrome have increased 24-hour urinary excretion of
cortisol. Further studies, including suppression or stimulation tests, measurement of serum corticotropin
(adrenocorticotropic hormone) concentrations, and imaging are usually necessary to confirm the diagnosis
and determine the etiology. Values in the normal range may occur in patients with mild Cushing
syndrome or with periodic hormonogenesis. In these cases, continuing follow-up and repeat testing are
necessary to confirm the diagnosis. Patients with Cushing syndrome due to intake of synthetic
glucocorticoids should have suppressed cortisol. In these circumstances a synthetic glucocorticoid screen
might be ordered (SGSU / Synthetic Glucocorticoid Screen, Urine). Suppressed cortisol values may also
be observed in primary adrenal insufficiency and hypopituitarism. The optimal specimen type for
evaluation of primary adrenal insufficiency and hypopituitarism is serum (CORT / Cortisol, Serum).
Reference Values:
Males
0-2 years: 3.0-120 mcg/g creatinine
3-8 years: 2.2-89 mcg/g creatinine
9-12 years: 1.4-56 mcg/g creatinine
13-17 years: 1.0-42 mcg/g creatinine
> or =18 years: 1.0-119 mcg/g creatinine
Females
0-2 years: 3.0-120 mcg/g creatinine
3-8 years: 2.2-89 mcg/g creatinine
9-12 years: 1.4-56 mcg/g creatinine
13-17 years: 1.0-42 mcg/g creatinine
> or =18 years: 0.7-85 mcg/g creatinine
Use the conversion factors below to convert each analyte from mcg/g creatinine to nmol/mol creatinine.
Conversion factor
Cortisol: mcg/g creatinine x 413=nmol/mol creatinine
Clinical References: 1. Findling JW, Raff H: Diagnosis and differential diagnosis of Cushing's
syndrome. Endocrinol Metab Clin North Am 2001;30:729-747 2. Boscaro M, Barzon L, Fallo F, Sonino
N: Cushing's syndrome. Lancet 2001;357:783-791 3. Taylor RL, Machacek D, Singh RJ: Validation of a
high-throughput liquid chromatography-tandem mass spectrometry method for urinary cortisol and
cortisone. Clin Chem 2002;48:1511-1519
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CRAV Cortisol, Right Adrenal Vein, Serum
6345 Reference Values:
No established reference values
Useful For: Screening for Cushing syndrome Diagnosis of Cushing syndrome in patients presenting
with symptoms or signs suggestive of the disease
Reference Values:
7 a.m.-9 a.m.: 100-750 ng/dL
3 p.m.-5 p.m.: <401 ng/dL
11 p.m.-midnight: <100 ng/dL
Clinical References: 1. Raff H, Raff JL, Findling JW: Late-night salivary cortisol as a screening
test for Cushing's syndrome. J Clin Endocrinol Metab 1998;83:2681-2686 2. Papanicolaou DA, Mullen
N, Kyrou I, Nieman LK: Nighttime salivary cortisol: a useful test for the diagnosis of Cushing's
syndrome. J Clin Endocrinol Metab 2002;87:4515-4521
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and albumin. Normally, <5% of circulating cortisol is free (unbound). The "free" cortisol is the
physiologically active form. Free cortisol is filterable by the renal glomerulus. Although
hypercortisolism is uncommon, the signs and symptoms are common (eg, obesity, high blood pressure,
increased blood glucose concentration). The most common cause of increased plasma cortisol levels in
women is a high circulating concentration of estrogen (eg, estrogen therapy, pregnancy) resulting in
increased concentration of cortisol-binding globulin. Spontaneous Cushing syndrome results from
overproduction of glucocorticoids as a result of either primary adrenal disease (adenoma, carcinoma, or
nodular hyperplasia) or an excess of ACTH (from a pituitary tumor or an ectopic source).
ACTH-dependent Cushing syndrome due to a pituitary corticotroph adenoma is the most frequently
diagnosed subtype; most commonly seen in women in the third through the fifth decades of life. The
onset is insidious and usually occurs 2 to 5 years before a clinical diagnosis is made. Causes of
hypocortisolism are: -Addison disease-primary adrenal insufficiency -Secondary adrenal insufficiency:
--Pituitary insufficiency --Hypothalamic insufficiency -Congenital adrenal hyperplasia-defects in
enzymes involved in cortisol synthesis
Useful For: Discrimination between primary and secondary adrenal insufficiency Differential
diagnosis of Cushing syndrome
Reference Values:
a.m.: 7-25 mcg/dL
p.m.: 2-14 mcg/dL
Clinical References: 1. Findling JW, Raff H: Diagnosis and differential diagnosis of Cushing's
syndrome. Endocrinol Metab Clin North Am 2001;30(3):729-747 2. Buchman AL: Side effects of
corticosteroid therapy. J Clin Gastroenterol 2001;33(4):289-294
Useful For: Second-order testing when cortisol measurement by immunoassay (eg, CORT / Cortisol,
Serum) gives results that are not consistent with clinical symptoms, or if patients are known to, or
suspected of, taking exogenous synthetic steroids. For confirming the presence of synthetic steroids,
order SGSS / Synthetic Glucocorticoid Screen, Serum. An adjunct in the differential diagnosis of
primary and secondary adrenal insufficiency An adjunct in the differential diagnosis of Cushing
syndrome
Reference Values:
5-25 mcg/dL (a.m.)
2-14 mcg/dL (p.m.)
Pediatric reference ranges are the same as adults, as confirmed by peer-reviewed literature.
Petersen KE: ACTH in normal children and children with pituitary and adrenal diseases. I.
Measurement in plasma by radioimmunoassay-basal values. Acta Paediatr Scand 1981;70:341-345
Clinical References: 1. Lin CL, Wu TJ, Machacek DA, et al: Urinary free cortisol and cortisone
determined by high-performance liquid chromatography in the diagnosis of Cushing's syndrome. J Clin
Endocrinol Metab 1997;82:151-155 2. Findling JW, Raff H: Diagnosis and differential diagnosis of
Cushing's syndrome. Endocrinol Metab Clin North Am 2001;30(3):729-747 3. Buchman Al: Side
effects of corticosteroid therapy. J Clin Gastroenterol 2001;33(4):289-297 4. Dodds HM, Taylor PJ,
Cannell GR, Pond SM: A high-performance liquid chromatography-electrospray-tandem mass
spectrometry analysis of cortisol and metabolites in placental perfusate. Anal Biochem
1997;247:342-347
Useful For: Screening test for Cushing syndrome (hypercortisolism) Assisting in diagnosing acquired
or inherited abnormalities of 11-beta-hydroxy steroid dehydrogenase (cortisol to cortisone ratio)
Diagnosis of pseudo-hyperaldosteronism due to excessive licorice consumption This test has limited
usefulness in the evaluation of adrenal insufficiency.
Interpretation: Most patients with Cushing syndrome have increased 24-hour urinary excretion of
cortisol and/or cortisone. Further studies, including suppression or stimulation tests, measurement of
serum corticotropin (adrenocorticotropic hormone) concentrations, and imaging are usually necessary to
confirm the diagnosis and determine the etiology. Values in the normal range may occur in patients with
mild Cushing syndrome or with periodic hormonogenesis. In these cases, continuing follow-up and repeat
testing are necessary to confirm the diagnosis. Patients with Cushing syndrome due to intake of synthetic
glucocorticoids should have both suppressed cortisol and cortisone. In these circumstances a synthetic
glucocorticoid screen might be ordered (call 800-533-1710). Suppressed cortisol and cortisone values may
also be observed in primary adrenal insufficiency and hypopituitarism. However, random urine specimens
are not useful for evaluation of hypocorticalism. Further, many normal individuals also may exhibit a very
low 24-hour urinary cortisol excretion with considerable overlap with the values observed in pathological
hypocorticalism. Therefore, without other tests, 24-hour urinary cortisol measurements cannot be relied
upon for the diagnosis of hypocorticalism. Patients with 11-beta HSD deficiency may have cortisone to
cortisol ratios <1, whereas a ratio of 2:1 to 3:1 is seen in normal patients. Excessive licorice consumption
and use of carbenoxolone, a synthetic derivative of glycyrrhizinic acid used to treat gastroesophageal
reflux disease, also may suppress the ratio to <1.
Reference Values:
CORTISOL
0-2 years: not established
3-8 years: 1.4-20 mcg/24 hours
9-12 years: 2.6-37 mcg/24 hours
13-17 years: 4.0-56 mcg/24 hours
> or =18 years: 3.5-45 mcg/24 hours
CORTISONE
0-2 years: not established
3-8 years: 5.5-41 mcg/24 hours
9-12 years: 9.9-73 mcg/24 hours
13-17 years: 15-108 mcg/24 hours
> or =18 years: 17-129 mcg/24 hours
Use the factors below to convert each analyte from mcg/24 hours to nmol/24 hours:
Conversion factors
Cortisol: mcg/24 hours x 2.76=nmol/24 hours (molecular weight=362.5)
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Cortisone: mcg/24 hours x 2.78=nmol/24 hours (molecular weight=360)
Clinical References: 1. Findling JW, Raff H: Diagnosis and differential diagnosis of Cushing's
syndrome. Endocrinol Metab Clin North Am 2001;30:729-747 2. Boscaro M, Barzon L, Fallo F, Sonino
N: Cushing's syndrome. Lancet 2001;357:783-791 3. Taylor RL, Machacek D, Singh RJ: Validation of
a high-throughput liquid chromatography-tandem mass spectrometry method for urinary cortisol and
cortisone. Clin Chem 2002;48:1511-1519
Interpretation: Most patients with Cushing syndrome have increased urinary excretion of cortisol
and/or cortisone. Further studies, including suppression or stimulation tests, measurement of serum
corticotrophin concentrations, and imaging are usually necessary to confirm the diagnosis and
determine the etiology. Values in the normal range may occur in patients with mild Cushing syndrome
or with periodic hormonogenesis. In these cases, continuing follow-up and repeat testing are necessary
to confirm the diagnosis. Patients with Cushing syndrome due to intake of synthetic glucocorticoids
should have both suppressed cortisol and cortisone. In these circumstances a synthetic glucocorticoid
screen might be ordered (SGSU / Synthetic Glucocorticoid Screen, Urine). Suppressed cortisol and
cortisone values may also be observed in primary adrenal insufficiency and hypopituitarism. However,
random urine specimens are not useful for evaluation of hypocorticalism. Patients with 11-beta HSD
deficiency may have cortisone to cortisol ratios less than 1, whereas a ratio of 2 or 3:1 is seen in normal
patients. Excessive licorice consumption and use of carbenoxolone, a synthetic derivative of
glycyrrhizinic acid used to treat gastroesophageal reflux disease, also may suppress the ratio to less than
1.
Reference Values:
CORTISOL
Males
0-2 years: 3.0-120 mcg/g creatinine
3-8 years: 2.2-89 mcg/g creatinine
9-12 years: 1.4-56 mcg/g creatinine
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13-17 years: 1.0-42 mcg/g creatinine
> or =18 years: 1.0-119 mcg/g creatinine
Females
0-2 years: 3.0-120 mcg/g creatinine
3-8 years: 2.2-89 mcg/g creatinine
9-12 years: 1.4-56 mcg/g creatinine
13-17 years: 1.0-42 mcg/g creatinine
> or =18 years: 0.7-85 mcg/g creatinine
CORTISONE
0-2 years: 25-477 mcg/g creatinine
3-8 years: 11-211 mcg/g creatinine
9-12 years: 5.8-109 mcg/g creatinine
13-17 years: 5.4-102 mcg/g creatinine
18-29 years: 5.7-153 mcg/g creatinine
30-39 years: 6.6-176 mcg/g creatinine
40-49 years: 7.6-203 mcg/g creatinine
50-59 years: 8.8-234 mcg/g creatinine
60-69 years: 10-270 mcg/g creatinine
> or =70 years: 12-311 mcg/g creatinine
Use the conversion factors below to convert each analyte from mcg/g creatinine to nmol/mol
creatinine:
Conversion factors
Cortisol: mcg/g creatinine x 413=nmol/mol creatinine
Cortisone: mcg/g creatinine x 415=nmol/mol creatinine
Clinical References: 1. Findling JW, Raff H: Diagnosis and differential diagnosis of Cushing's
syndrome. Endocrinol Metab Clin North Am 2001;30:729-747 2. Boscaro M, Barzon L, Fallo F, Sonino
N: Cushing's syndrome. Lancet 2001;357:783-791 3. Taylor RL, Machacek D, Singh RJ: Validation of a
high-throughput liquid chromatography-tandem mass spectrometry method for urinary cortisol and
cortisone. Clin Chem 2002;48:1511-1519
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disease relates to production phage-encoded diphtheria toxin. Since isolates of Corynebacterium
diphtheriae may or may not harbor genes to produce the toxin, they should be further tested for diphtheria
toxin production. A negative result is evidence against a diagnosis of diphtheria but does not definitively
rule out this disease since culture may be negative because of prior antimicrobial therapy or organism
present below the limit of detection of the assay.
Reference Values:
No growth of Corynebacterium diphtheriae
Clinical References: Mandell GL, Bennett JE, Dolin R: In Principles and Practice of Infectious
Diseases. Sixth edition. Philadelphia, PA, Elsevier Inc, 2005, pp 2457-2465
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
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CSED Cottonseed, IgE
82804 Clinical Information: Clinical manifestations of immediate hypersensitivity (allergic) diseases are
caused by the release of proinflammatory mediators (histamine, leukotrienes, and prostaglandins) from
immunoglobulin E (IgE)-sensitized effector cells (mast cells and basophils) when cell-bound IgE
antibodies interact with allergen. In vitro serum testing for IgE antibodies provides an indication of the
immune response to allergen(s) that may be associated with allergic disease. The allergens chosen for
testing often depend upon the age of the patient, history of allergen exposure, season of the year, and
clinical manifestations. In individuals predisposed to develop allergic disease(s), the sequence of
sensitization and clinical manifestations proceed as follows: eczema and respiratory disease (rhinitis and
bronchospasm) in infants and children less than 5 years due to food sensitivity (milk, egg, soy, and wheat
proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
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Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
4 17.5-49.9 Strongly positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
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0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Clinical References: 1. van Hattem WA, Brosens LA, Marks SY, et al: Increased cyclooxygenase-2
expression in juvenile polyposis syndrome. Clin Gastroenterol Hepatol 2009 Jan;7(1):93-97 2. Milne AN,
Carvalho R, Morsink FM, et al: Early-onset gastric cancers have a different molecular expression profile
than conventional gastric cancers. Mod Pathol 2006 April;19(4):564-572 3. Sheehan KM, Steele C,
Sheahan K, et al: Association between cyclooxygenase-2-expressing macrophages, ulceration and
microvessel density in colorectal cancer. Histopathology 2005 March;46(3):287-295
Clinical References: 1. Marrie TJ, Raoult D: Coxiella burnetii (Q fever). In Mandell, Douglas,
and Bennett's Principles and Practice of Infectious Diseases. Edited by GL Mandell, JE Bennett, R
Dolin. Seventh edition. Philadelphia, PA. Churchill Livingstone/Elsevier, 2010, pp 2511-2519 2.
Maurin M, Raoult D: Q fever. Clin Microbiol Rev 1999;12:518-533 3. Fenollar F, Fournier PE, Raoult
D: Molecular detection of Coxiella burnetii in the sera of patients with Q fever endocarditis or vascular
infection. J Clin Microbiol 2004;42:4919-4924 4. Fournier PE, Raoult D: Comparison of PCR and
serology assays for early diagnosis of acute Q fever. J Clin Microbiol 2003;41:5094-5098 5. Tande A,
Cunningham S, Raoult D, et al: Coxiella burnetii prosthetic joint infection-case report and assay for
detection. J Clin Microbiol 2013;51:66-69 6. Frangoulidis D, Meyer H, Kahlhofer C, Splettstoesser
WD: 'Real-time' PCR-based detection of Coxiella burnetii using conventional techniques. FEMS
Immunol Med Microbiol 2012;64:134-136 7. CDC Releases First National Guidelines on Managing Q
Fever. JAMA 2013;309(18):1887 8. Anderson A, Bijlmer H, Fournier PE, et al: Diagnosis and
management of Q fever-United States, 2013: recommendations from CDC and the Q Fever Working
Group. MMWR Recomm Rep 2013;62(RR-03):1-30
Reference Values:
Not applicable
Clinical References: 1. Marrie TJ, Raoult D: Coxiella burnetii (Q fever). In Mandell, Douglas,
and Bennett's Principles and Practice of Infectious Diseases. Edited by GL Mandell, JE Bennett, R
Dolin. Seventh edition. Philadelphia, PA. Churchill Livingstone/Elsevier, 2010, pp 2511-2519 2.
Maurin M, Raoult D: Q fever. Clin Microbiol Rev 1999;12:518-533 3. Fenollar F, Fournier PE, Raoult
D: Molecular detection of Coxiella burnetii in the sera of patients with Q fever endocarditis or vascular
infection. J Clin Microbiol 2004;42:4919-4924 4. Fournier PE, Raoult D: Comparison of PCR and
serology assays for early diagnosis of acute Q fever. J Clin Microbiol 2003;41:5094-5098 5. Tande A,
Cunningham S, Raoult D, et al: Coxiella burnetii prosthetic joint infection-case report and assay for
detection. J Clin Microbiol 2013;51:66-69 6. Frangoulidis D, Meyer H, Kahlhofer C, Splettstoesser
WD: 'Real-time' PCR-based detection of Coxiella burnetii using conventional techniques. FEMS
Immunol Med Microbiol 2012;64:134-136 7. CDC Releases First National Guidelines on Managing Q
Fever. JAMA 2013;309(18):1887 8. Anderson A, Bijlmer H, Fournier PE, et al: Diagnosis and
management of Q fever-United States, 2013: recommendations from CDC and the Q Fever Working
Group. MMWR Recomm Rep 2013;62(RR-03):1-30
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CBSRP Coxiella burnetii (Q Fever), Molecular Detection, PCR, Serum
62194 Clinical Information: Coxiella burnetii, the causative agent of Q fever, is a small obligately
intracellular bacterium, which is associated with animals. It is acquired through aerosol exposure and
generally causes mild respiratory disease. A small number of acute cases advance to a chronic infection,
which typically manifests as endocarditis. Left untreated, Q fever endocarditis may be fatal. Serologic and
histopathologic studies may be nonspecific and subjective, respectively, limiting usefulness for patient
diagnosis. Evaluation of infected tissue, blood, or serum using PCR may be a useful tool for diagnosing
some cases of Coxiella burnetii infection. Mayo Medical Laboratories has developed a real-time PCR test
that rapidly detects Coxiella burnetii DNA in clinical specimens by targeting a sequence of the shikimate
dehydrogenase gene (aroE) unique to Coxiella burnetii.
Reference Values:
Not applicable
INTERPRETIVE CRITERIA:
< 1:1 Antibody Not Detected
> or = 1:1 Antibody Detected
Diagnosis of infections of the central nervous system is accomplished by demonstrating the presence of
intrathecally-produced specific antibody. Interpretation of results may be complicated by low antibody
levels found in CSF, passive transfer of antibody from blood, and contamination via bloody taps. The
interpretation of CSF results must consider CSF-serum antibody ratios to the infectious agent.
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INTERPRETIVE CRITERIA:
<1:8 Antibody Not Detected
> or = 1:8 Antibody Detected
Single titers of > or = 1:32 are indicative of recent infection. Titers of 1:8 or 1:16 may be indicative of
either past or recent infection, since CF antibody levels persist for only a few months. A four-fold or
greater increase in titer between acute and convalescent specimens confirms the diagnosis. There is
considerable crossreactivity among enteroviruses; however, the highest titer is usually associated with the
infecting serotype.
Interpretive Criteria:
< 1:1 Antibody Not Detected
> or = 1:1 Antibody Detected
Diagnosis of infections of the central nervous system is accomplished by demonstrating the presence
of intrathecally-produced specific antibody. Interpretation of results may be complicated by low
antibody levels found in CSF, passive transfer of antibody from blood, and contamination via bloody
taps. The interpretation of CSF results must consider CSF-serum antibody ratios to the infectious agent.
Single titers of > or = 1:32 are indicative of recent infection. Titers of 1:8 or 1:16 may be indicative
of either past or recent infection, since CF antibody levels persist for only a few months. A four-fold or
greater increase in titer between acute and convalescent specimens confirms the diagnosis. There is
considerable crossreactivity among enteroviruses; however, the highest titer is usually associated with
the infecting serotype.
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endogenous and exogenous triggers. These triggers include porphyrogenic drugs, hormonal
contraceptives, fasting, alcohol, tobacco, and cannabis. Fecal porphyrins analysis and quantitative
urinary porphyrins analysis are helpful in distinguishing HCP from other forms of acute porphyria.
Useful For: Confirmation of hereditary coproporphyria (HCP) for patients with clinical features This
test should be ordered only for individuals with symptoms suggestive of HCP. Asymptomatic patients
with a family history of HCP should not be tested until a mutation has been identified in an affected
family member.
Interpretation: All detected alterations are evaluated according to American College of Medical
Genetics recommendations.(1) Variants are classified based on known, predicted, or possible
pathogenicity and reported with interpretive comments detailing their potential or known significance.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for
standards of interpretation and reporting of sequence variations: revisions 2007. Genet Med
2008;10(4):294-300 2. Siegesmund M, van Tuyll van Serooskerken AM, Poblete-Gutierrez P, et al: The
acute hepatic porphyrias: current status and future challenges. Best Pract Res Clin Gastroenterol 2010
Oct;24(5):593-605 3. Anderson KE, Bloomer JR, Bonkovsky HL, et al: Recommendations for the
diagnosis and treatment of the acute porphyrias. Ann Intern Med 2005 Mar 15;142(6):439-450 4. Schmitt,
C, Gouya L, Malonova E, et al: Mutations in human CPO gene predict clinical expression of either
hereditary coproporphyria or erythropoietic harderoporphyria. Hum Mol Genet 2005;14(20):3089-3098
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical utility
of food-specific IgG tests has not been established. These tests can be used in special clinical situations to
select foods for evaluation by diet elimination and challenge in patients who have food-related
complaints. It should be recognized that the presence of food-specific IgG alone cannot be taken as
evidence of food allergy and only indicates immunologic sensitization by the food allergen in question.
This test should only be ordered by physicians who recognize the limitations of the test.
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
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allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 613
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
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CRDPU Creatine Disorders Panel, Urine
88697 Clinical Information: Disorders of creatine synthesis (deficiency of arginine:glycine
amidinotransferase [AGAT] and guanidinoacetate methyltransferase [GAMT]) and creatine transporter
(SLC6A8) deficiency are collectively described as creatine deficiency syndromes (CDS). AGAT and
GAMT deficiencies are inherited in an autosomal recessive manner, while the creatine transporter
defect is X-linked. All 3 disorders result in a depletion of cerebral creatine and typically present with
global developmental delays, intellectual disability, and severe speech delay. Commonly, patients with
CDS develop seizures. Patients with GAMT and the creatine transporter deficiency exhibit behavioral
problems and features of autism. Female carriers for the creatine transporter deficiency can have
intellectual disability and behavioral problems, and some develop seizures. Diagnosis is possible by
measuring guanidinoacetate (GAA), creatine (Cr), and creatinine (Crn) in plasma and urine. The
profiles are specific for each clinical entity. Patients with GAMT deficiency typically exhibit normal to
low Cr, very elevated GAA, and low Crn. Patients with AGAT deficiency typically exhibit normal to
low Cr, low GAA, and normal to low Crn. In comparison, elevated Cr, normal GAA, normal to low
Crn, and an elevated Cr:Crn ratio characterize patients with creatine transporter defect. Treatment with
oral supplementation of creatine monohydrate is available and effective for the AGAT and GAMT
deficiencies. Creatine supplementation has not been shown to improve outcomes in males with the
creatine transporter defect. Female carriers of creatine transporter deficiency who have symptoms,
however, have been reported to benefit from creatine supplementation.
Useful For: Evaluation of patients with a clinical suspicion of inborn errors of creatine metabolism
including arginine:glycine amidinotransferase deficiency, guanidinoacetate methyltransferase
deficiency, and creatine transporter (SLC6A8) defect
Reference Values:
Age Creatinine (nmol/mL) Guanidinoacetate (nmol/mL) Creatine (nmol/mL) Creatine/ Creatinine
Clinical References: 1. Clark JF, Cecil KM: Diagnostic methods and recommendations for the
cerebral creatine deficiency syndromes. Pediatr Res 2015 Mar;77(3):398-405 2. Mercimek-Mahmutoglu
S, Salomons GS: Creatine Deficiency Syndromes. In GeneReviews. Edited by RA Pagon, MP Adam,
HH Ardinger, et al: University of Washington, Seattle; 1993-2017. Updated 2009 Jan 15. Available at
https://www.ncbi.nlm.nih.gov/books/NBK3794/ 3. Stockler S, Schultz PW, Salomons GS: Cerebral
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 615
creatine deficiency syndromes: clinical aspects, treatment and pathophysiology. Subcell Biochem
2007;46:149-166 4. Longo N, Ardon O, Vanzo R, et al: Disorders of creatine transport and metabolism.
Am J Med Genet 2011;157:72-78 doi: 10.1002/ajmg.c.30292
Useful For: Serial quantitation of serum creatine kinase MB (CKMB) levels, often performed at
admission and 8-hours, 16-hours, and 24-hours after admission, has traditionally been used as an aid in
the diagnosis of myocardial injury May be useful if the initial troponin determination is abnormal or if a
hospitalized patient has a suspected reinfarction
Interpretation: Creatine kinase MB (CKMB) levels can be detected within 3 to 8 hours of the onset of
chest pain, peak within 12 to 24 hours, and usually return to baseline levels within 24 to 48 hours.
Reference Values:
Males: < or =7.7 ng/mL
Females: < or =4.3 ng/mL
Useful For: The determination of creatine kinase is utilized in the diagnosis and monitoring of
myocardial infarction and myopathies such as the progressive Duchenne muscular dystrophy.
Interpretation: Serum creatine kinase (CK) activity is greatly elevated, at some time during the course
of the disease, in all types of muscular dystrophy, and especially so in Duchenne type, in which levels up
to 50 times the upper limit of normal may be encountered. In progressive muscular dystrophy, enzyme
activity in serum is highest in infancy and childhood (7-10 years of age) and may be elevated long before
the disease is clinically apparent. Quite high values of CK are noted in viral myositis, polymyositis, and
similar muscle diseases. However, in neurogenic Parkinsonism, serum enzyme activity is normal. Very
high activity is also encountered in malignant hyperthermia. An early rise in CK is also seen after an acute
MI, with values peaking at 12 to 24 hours and falling back to normal in 3 to 4 days. Although total CK
activity has been used as a diagnostic test for MI, it has been replaced by the troponin T and I
immunoassays, and is no longer the laboratory test choice for diagnosing and monitoring acute
infarctions. Serum CK activity may increase in patients with acute cerebrovascular disease or
neurosurgical intervention and with cerebral ischemia. Serum CK activity also demonstrates an inverse
relationship with thyroid activity. About 60% of hypothyroid subjects show an average elevation of CK
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activity 5-fold over the upper reference limit; elevation of as high as 50-fold may also be found.
Reference Values:
Males
6-11 years: 150-499 U/L
12-17 years: 94-499 U/L
> or =18 years: 52-336 U/L
Females
6-7 years: 134-391 U/L
8-14 years: 91-391 U/L
15-17 years: 53-269 U/L
> or =18 years: 38-176 U/L
Reference values have not been established for patients that are less than 6 years of age.
Note: Strenuous exercise or intramuscular injections may cause transient elevation of CK.
Useful For: Detection of macro forms of creatine kinase Diagnosing skeletal muscle disease, in
conjunction with aldolase
Interpretation: Creatine kinase (CK)-MB appears in serum 4 to 6 hours after the onset of pain in a
myocardial infarction, peaks at 18 to 24 hours, and may persist for 72 hours. CK-MB may also be
elevated in cases of carbon monoxide poisoning, pulmonary embolism, hypothyroidism, crush injuries,
and muscular dystrophy. Extreme elevations of CK-MB can be associated with skeletal muscle cell
turnover as in polymyositis, and to a lesser degree in rhabdomyolysis, as seen in strenuous exercise,
particularly in the conditioned athlete. CK-BB can be elevated in patients with head injury, in neonates,
and in some cancers such as prostate cancer and small cell carcinoma of the lung. It can also be elevated
in other malignancies; however, the clinical usefulness of CK-BB as a tumor marker needs further
investigation. The presence of macro CK can explain an elevation of total CK. It does not rise and fall
as rapidly as CK-MM and CK-MB in muscle injury. Macro CK type II (mitochondrial CK) is rarely
observed. It is only seen in acutely ill patients with malignancies and other severe illnesses with a high
associated mortality, such as liver disease and hypoxic injury.
Reference Values:
CREATINE KINASE, TOTAL
Males
6-11 years: 150-499 U/L
12-17 years: 94-499 U/L
> or =18 years: 52-336 U/L
Females
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6-7 years: 134-391 U/L
8-14 years: 91-391 U/L
15-17 years: 53-269 U/L
> or =18 years: 38-176 U/L
Reference values have not been established for patients that are less than 6 years of age.
Note: Strenuous exercise or intramuscular injections may cause transient elevation of CK.
Clinical References: Apple FS, Quist HE, Doyle PJ, et al: Plasma 99th percentile reference limits
for cardiac troponin and creatine kinase MB mass for use with European Society of Cardiology/American
College of Cardiology consensus recommendations. Clin Chem 2003 Aug;49(8):1331-1336
Reference Values:
Creatinine Clearance:
Males:
0-18 years: Reference values have not been established
19-75 years: 77-160 mL/min/BSA
> or =76 years: Reference values have not been established
Females:
0-17 years: Reference values have not been established
18-29 years: 78-161 mL/min/BSA
30-39 years: 72-154 mL/min/BSA
40-49 years: 67-146 mL/min/BSA
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50-59 years: 62-139 mL/min/BSA
60-72 years: 56-131 mL/min/BSA
> or =73 years: Reference values have not been established
Creatinine, Urine: reported in units of mg/dL
Creatinine, Serum
Males
12-24 months: 0.1-0.4 mg/dL
3-4 years: 0.1-0.5 mg/dL
5-9 years: 0.2-0.6 mg/dL
10-11 years: 0.3-0.7 mg/dL
12-13 years: 0.4-0.8 mg/dL
14-15 years: 0.5-0.9 mg/dL
> or =16 years: 0.8-1.3 mg/dL
Reference values have not been established for patients that are less than 12 months of age.
Females
13-36 months: 0.1-0.4 mg/dL
4-5 years: 0.2-0.5 mg/dL
6-8 years: 0.3-0.6 mg/dL
9-15 years: 0.4-0.7 mg/dL
> or =16 years: 0.6-1.1 mg/dL
Reference values have not been established for patients that are less than 12 months of age.
Clinical References: 1. Post TW, Rose BD: Assessment of renal function: plasma creatinine;
BUN; and GFR. In UpTo Date 9.1. Edited by BD Rose. 2001 2. Kasiske BL, Keane WF: Laboratory
assessment of renal disease: clearance, urinalysis, and renal biopsy. In The Kidney. Sixth edition. Edited
by BM Brenner. Philadelphia, WB Saunders Company, 2000, pp 1129-1170
Useful For: Creatinine: -Diagnosing and monitoring treatment of acute and chronic renal diseases
-Adjusting dosage of renally excreted medications -Monitoring renal transplant recipients Estimated
Glomerular Filtration Rate (eGFR): Serum creatinine measurement is used in estimating GFR for people
with chronic kidney disease (CKD) and those with risk factors for CKD (diabetes, hypertension,
cardiovascular disease, and family history of kidney disease).
Interpretation: Creatinine: Because serum creatinine is inversely correlated with glomerular filtration
rate (GFR), when renal function is near normal, absolute changes in serum creatinine reflect larger
changes than do similar absolute changes when renal function is poor. For example, an increase in serum
creatinine from 1 to 2 mg/dL may indicate a decrease in GFR of 50 mL/min (from 100 to 50 mL/min),
whereas an increase in serum creatinine level from 4 to 5 mg/dL may indicate a decrease of only 5
mL/min (from 25 to 20 mL/min). Because of the imprecision of serum creatinine as an assessment of
GFR, there may be clinical situations where a more accurate GFR assessment must be performed,
iothalamate or inulin clearance are superior to serum creatinine. Several factors may influence serum
creatinine independent of changes in GFR. For instance, creatinine generation is dependent upon muscle
mass. Thus, young, muscular males may have significantly higher serum creatinine levels than elderly
females, despite having similar GFRs. Also, because some renal clearance of creatinine is due to tubular
secretion, drugs that inhibit this secretory component (eg, cimetidine and trimethoprim) may cause small
increases in serum creatinine without an actual decrease in GFR. Estimated GFR: Chronic kidney disease
(CKD) is defined as the presence of: persistent and usually progressive reduction in GFR (GFR <60
mL/min/1.73 m[2]) and/or albuminuria (>30 mg of urinary albumin per gram of urinary creatinine),
regardless of GFR. According to the National Kidney Foundation Kidney Disease Outcome Quality
Initiative (K/DOQI) classification, among patients with CKD, irrespective of diagnosis, the stage of
disease should be assigned based on the level of kidney function: Stage Description GFR mL/min/1.73
m(2) 1 Kidney damage with normal or increased GFR 90 2 Kidney damage with mild decrease in GFR 60
to 89 3 Moderate decrease in GFR 30 to 59 4 Severe decrease in GFR 15 to 29 5 Kidney failure <15 (or
dialysis)
Reference Values:
CREATININE
Males
1-2 years: 0.1-0.4 mg/dL
3-4 years: 0.1-0.5 mg/dL
5-9 years: 0.2-0.6 mg/dL
10-11 years: 0.3-0.7 mg/dL
12-13 years: 0.4-0.8 mg/dL
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14-15 years: 0.5-0.9 mg/dL
> or =16 years: 0.8-1.3 mg/dL
Reference values have not been established for patients that are <12 months of age.
Females
1-3 years: 0.1-0.4 mg/dL
4-5 years: 0.2-0.5 mg/dL
6-8 years: 0.3-0.6 mg/dL
9-15 years: 0.4-0.7 mg/dL
> or =16 years: 0.6-1.1 mg/dL
Reference values have not been established for patients that are <12 months of age.
ESTIMATED GFR
>60 mL/min/BSA
Note: eGFR results will not be calculated for patients <18 or >70 years old.
Clinical References: 1. Levey AS, Coresh J, Balk E, et al: National Kidney Foundation practice
guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med
2003;139:137-147 2. Manjunath G, Sarnak MJ, Levey AS: Prediction equations to estimate glomerular
filtration rate: an update. Curr Opin Nephrol Hypertens 2001;10:785-792 3. National Kidney Disease
Education Program: Suggestions for Laboratories. Revised February 2007. Available from
http://http://nkdep.nih.gov/resources/laboratory_reporting.htm 4. Poggio ED, Wang X, Greene T, et al:
Performance of the modification of diet in renal disease and Cockcroft-Gault equations in the estimation
of GFR in health and in chronic kidney disease. J Am Soc Nephrol 2005:16:459-466 5. Myers GL,
Miller WG, Coresh J, et al: Recommendations for improving serum creatinine measurement: a report
from the laboratory working group of the National Kidney Disease Education Program. Clin Chem
2006;52:5-18 6. Poggio ED, Nef PC, Wang X, et al: Performance of the Cockcroft-Gault and
modification of diet in renal disease equations in estimating GFR in ill hospitalized patients. Am J
Kidney Dis 2005;46:242-252 7. Saenger AK, Lockwood C, Snozek CL, et al: Catecholamine
interference in enzymatic creatinine assays. Clin Chem 2009;55(9):1732-1736
Useful For: Urinary creatinine, in conjunction with serum creatinine, is used to calculate the
creatinine clearance, a measure of renal function.
Interpretation: 24-Hour urinary creatinine determinations are principally used for the calculation of
creatinine clearance. Decreased creatinine clearance indicates decreased glomerular filtration rate. This
can be due to conditions such as progressive renal disease, or result from adverse effect on renal
hemodynamics that are often reversible including certain drugs or from decreases in effective renal
perfusion (eg, volume depletion or heart failure). Increased creatinine clearance is often referred to as
"hyperfiltration" and is most commonly seen during pregnancy or in patients with diabetes mellitus,
before diabetic nephropathy has occurred. It also may occur with large dietary protein intake.
Reference Values:
Normal values mg per 24 hours:
Males: 955-2936 mg/24 hours
Females: 601-1689 mg/24 hours
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 621
Reference ranges for male and female patients <18 and >83 years of age have not been established.
Reference ranges for male and female patients <18 and >83 years of age have not been established.
Note: To convert to mg/kg of body weight/24 hours, divide the mg/24 h result by body weight in kg.
Clinical References: 1. Newman DJ, Price CP: Renal function and nitrogen metabolites. In Tietz
Textbook of Clinical Chemistry. Thrid edition. Edited by CA Burtis, ER Ashwood. Philadelphia, WB
Saunders, 1999, pp 1204-1270 2. Kasiske BL, Keane WF: Laboratory assessment of renal disease:
clearance, urinalysis, and renal biopsy. In The Kidney. Sixth edition. Edited by BM Brenner.
Philadelphia, WB Saunders, 2000, pp 1129-1170
Useful For: Identifying the presence of urine as a cause for accumulation of fluid in a body
compartment
Interpretation: Body fluid to serum ratios >1.0 suggest the presence of urine in the sample.
Reference Values:
Not applicable
Clinical References: 1. Manahan KJ, Fanning J: Peritoneal fluid urea nitrogen and creatinine
reference values. Obstet Gynecol 1999;93:780-782 2. Wong MH, Lim SK, Ng KL, Ng KP: Pseudo-acute
kidney injury with recurrent ascites due to intraperitoneal urine leakage. Intern Med J 2012;42:848-849 3.
Nguyen-Khac E, Thevenot T, Capron D, et al: Are ascitic electrolytes usable in cirrhotic patients?
Correlation of sodium, potassium, chloride, urea, and creatinine concentrations in ascitic fluid and blood.
Eur J Intern Med 2008;19:613-618
Useful For: Urinary creatinine, in conjunction with serum creatinine, is used to calculate the creatinine
clearance, a measure of renal function. In a random specimen, urinary analytes can be normalized by the
creatinine concentration to account for the variation in urinary concentrations between subjects.
Interpretation: Decreased creatinine clearance indicates decreased glomerular filtration rate. This can
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 622
be due to conditions such as progressive renal disease, or result from adverse effect on renal
hemodynamics that are often reversible including certain drugs or from decreases in effective renal
perfusion (eg, volume depletion or heart failure). Increased creatinine clearance is often referred to as
"hyperfiltration" and is most commonly seen during pregnancy or in patients with diabetes mellitus,
before diabetic nephropathy has occurred. It also may occur with large dietary protein intake.
Reference Values:
No established reference values
Clinical References: 1. Newman DJ, Price CP: Renal function and nitrogen metabolites. In Tietz
Textbook of Clinical Chemistry. Third edition. Edited by CA Burtis, ER Ashwood. Philadelphia, WB
Saunders Company, 1999, pp 1204-1270 2. Kasiske BL, Keane WF: Laboratory assessment of renal
disease: clearance, urinalysis, and renal biopsy. In The Kidney. Sixth edition. Edited by BM Brenner.
Philadelphia, WB Saunders Company, 2000, pp 1129-1170
Interpretation: Any individual with a normal signal pattern (2 signals) in each metaphase is
considered negative for a deletion in the region tested by this probe (see Cautions). Any patient with a
FISH signal pattern indicating loss of the critical region will be reported as having a deletion of the
region tested by this probe.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Mainardi PC, Perfumo C, Cali A, et al: Clinical and molecular
characterization of 80 patients with 5p deletion: genotype-phenotype correlation. J Med Genet
2001;38:151-158 2. Mainardi PC: Cri du Chat syndrome. Orphanet J Rare Dis 2006;1:33
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 623
(polyclonal--in which no monoclonal protein is found) Type I cryoglobulinemia is associated with
monoclonal gammopathy of undetermined significance, macroglobulinemia, or multiple myeloma. Type
II cryoglobulinemia is associated with autoimmune disorders such as vasculitis, glomerulonephritis,
systemic lupus erythematosus, rheumatoid arthritis, and Sjogren's syndrome. It may be seen in
infections such as hepatitis, infectious mononucleosis, cytomegalovirus, and toxoplasmosis. Type II
cryoglobulinemia may also be essential, ie, occurring in the absence of underlying disease. Type III
cryoglobulinemia usually demonstrates trace levels of cryoprecipitate, may take up to 7 days to appear,
and is associated with the same disease spectrum as Type II cryoglobulinemia. A cryoprecipitate that is
seen in plasma but not in serum is caused by cryofibrinogen. Cryofibrinogens are extremely rare and
can be associated with vasculitis. Due to the rarity of clinically significant cryofibrinogenemia, testing
for cryoglobulins is usually sufficient for investigation of cryoproteins.
Useful For: Evaluating patients with vasculitis, glomerulonephritis, and lymphoproliferative diseases
Evaluating patients with macroglobulinemia or myeloma in whom symptoms occur with cold exposure
CRYOFIBRINOGEN
Negative
Quantitation and immunotyping will not be performed on positive cryofibrinogen.
Clinical References: Kyle RA, Lust JA: Immunoglobulins and laboratory recognition of monoclonal
proteins. Section III. Myeloma and related disorders. In Neoplastic Diseases of the Blood. Third edition.
Edited by PH Wiernik, GP Canellos, JP Dutcher, RA Kyle. New York, Churchill Livingstone, 1996, pp
453-475
Useful For: Evaluating patients with vasculitis, glomerulonephritis, and lymphoproliferative diseases
Evaluating patients with macroglobulinemia or myeloma in whom symptoms occur with cold exposure
Clinical References: Kyle RA, Lust JA: Immunoglobulins and laboratory recognition of monoclonal
proteins. Section III. Myeloma and related disorders. In Neoplastic Diseases of the Blood. Third edition.
Edited by PH Wiernik, GP Canellos, JP Dutcher, RA Kyle. New York, Churchill Livingstone, 1996, pp
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 624
453-475
Reference Values:
Negative
Clinical References: 1. Speed B, Dunt D: Clinical and host differences between infections with
the two varieties of Cryptococcus neoformans. Clin Infect Dis 1995;21(1):28-34 2. Chen S, Sorrell T,
Nimmo G, et al: Epidemiology and host- and variety-dependent characteristics of infection due to
Cryptococcus neoformans in Australia and New Zealand. Australasian Cyrptococcoal Study Group.
Clin Infect Dis 2000;31(2):499-505 3. Perfect JR, Dismukes WE, Dromer F, et al: Clinical practice
guidelines for the management of cryptococcal disease: 2010 update by the Infectious Diseases Society
of America. 2009;50:291-322 4. Warren NG, Hazen KC: Candida, Cryptococcus, and other yeasts of
medical importance. In Manual of Clinical Microbiology. Seventh edition. Edited by PR Murray.
Washington, DC, ASM Press, 1999, pp 1184-1199 5. Lu H, Zhou Y, Yin Y, et al: Cryptococcal antigen
test revisited: significance for cryptococcal meningitis therapy monitoring in a tertiary Chinese hospital.
J Clin Microbiol 2005 June;43(6):2989-2990
Reference Values:
Negative
Clinical References: 1. Speed B, Dunt D: Clinical and host differences between infections with the
two varieties of Cryptococcus neoformans. Clin Infect Dis 1995;21(1):28-34 2. Chen S, Sorrell T, Nimmo
G, et al: Epidemiology and host- and variety-dependent characteristics of infection due to Cryptococcus
neoformans in Australia and New Zealand. Australasian Cyrptococcoal Study Group. Clin Infect Dis
2000;31(2):499-505 3. Perfect JR, Dismukes WE, Dromer F, et al: Clinical practice guidelines for the
management of cryptococcal disease: 2010 update by the infectious diseases society of America. Clin
Infect Dis 2010;50:291-322 4. Warren NG, Hazen KC: Candida, Cryptococcus, and other yeasts of
medical importance. In Manual of Clinical Microbiology. Seventh edition. Edited by PR Murray.
Washington DC. ASM Press, 1999, pp 1184-1199 5. Lu H, Zhou Y, Yin Y, et al: Cryptococcal antigen
test revisited: significance for cryptococcal meningitis therapy monitoring in a tertiary Chinese hospital. J
Clin Microbiol 2005 June;43(6):2989-2990
Interpretation: The presence of cryptococcal antigen in any body fluid (serum or cerebrospinal
fluid: CSF) is indicative of cryptococcosis. Disseminated infection is usually accompanied by a positive
serum test. Declining titers may indicate regression of infection. However, monitoring titers to
cryptococcal antigen should not be used as a test of cure or to guide treatment decisions. Low-level
titers may persist for extended periods of time following appropriate therapy and resolution of
infection.(3,4)
Reference Values:
Negative
Clinical References: 1. Speed B, Dunt D: Clinical and host differences between infections with
the two varieties of Cryptococcus neoformans. Clin Infect Dis 1995;21(1):28-34 2. Chen S, Sorrell T,
Nimmo G, et al: Epidemiology and host- and variety-dependent characteristics of infection due to
Cryptococcus neoformans in Australia and New Zealand. Australasian Cyrptococcoal Study Group.
Clin Infect Dis 2000;31(2):499-505 3. Lu H, Zhou Y, Yin Y, et al: Cryptococcal antigen test revisited:
significance for cryptococcal meningitis therapy monitoring in a tertiary Chinese hospital. J Clin
Microbiol 2005 June;43(6):2989-2990 4. Perfect JR, Dismukes WE, Dromer F, et al: Clinical practice
guidelines for the management of cryptococcal disease: 2010 update by the Infectious Diseases Society
of America. Clin Infect Dis 2010;50:291-322 5. Binnicker MJ, Jespersen DJ, Bestrom JE, Rollins LO:
A comparison of four assays for detection of cryptococcal antigen. Clin Vaccine Immunol 2012
Dec;19(12):1988-1990 6. Warren NG, Hazen KC: Candida, Cryptococcus, and other yeasts of medical
importance. In Manual of Clinical Microbiology. Seventh edition. Edited by PR Murray. Washington
DC. ASM Press, 1999, pp 1184-1199
Useful For: Monitoring Cryptococcus antigen titers in cerebrospinal fluid Aiding in the diagnosis of
cryptococcosis
Interpretation: The presence of cryptococcal antigen in any body fluid (serum or cerebrospinal
fluid: CSF) is indicative of cryptococcosis. Disseminated infection is usually accompanied by a positive
serum test. Declining titers may indicate regression of infection. However, monitoring titers to
cryptococcal antigen should not be used as a test of cure or to guide treatment decisions. Low-level
titers may persist for extended periods of time following appropriate therapy and resolution of
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 627
infection.(3,4) CSF specimens submitted for initial diagnosis, which test positive by the lateral flow
assay, should also be submitted for routine fungal culture. Culture can aid to differentiate between the 2
common Cryptococcus species causing disease (Cryptococcus neoformans and Cryptococcus gattii) and
can be used for antifungal susceptibility testing, if necessary. CSF specimens submitted to monitor
antigen levels during treatment do not need to be cultured.
Reference Values:
Negative
Clinical References: 1. Speed B, Dunt D: Clinical and host differences between infections with the
two varieties of Cryptococcus neoformans. Clin Infect Dis 1995;21(1):28-34 2. Chen S, Sorrell T, Nimmo
G, et al: Epidemiology and host- and variety-dependent characteristics of infection due to Cryptococcus
neoformans in Australia and New Zealand. Australasian Cyrptococcoal Study Group. Clin Infect Dis
2000;31(2):499-505 3. Lu H, Zhou Y, Yin Y, et al: Cryptococcal antigen test revisited: significance for
cryptococcal meningitis therapy monitoring in a tertiary Chinese hospital. J Clin Microbiol 2005
June;43(6):2989-2990 4. Perfect JR, Dismukes WE, Dromer F, et al: Clinical practice guidelines for the
management of cryptococcal disease: 2010 update by the Infectious Diseases Society of America. Clin
Infect Dis 2010;50:291-322 5. Warren NG, Hazen KC: Candida, Cryptococcus, and other yeasts of
medical importance. In Manual of Clinical Microbiology. Seventh edition. Edited by PR Murray.
Washington DC. ASM Press, 1999, pp 1184-1199
FUNGAL CULTURE
Negative
If positive, fungus will be identified.
Reference Values:
Negative
Clinical References: Hazen KC, Howell,SA: Candida, Cryptococcus, and other Yeasts of Medical
Importance. In Manual of Clinical Microbiology. Ninth edition. Edited by PR Murray. Washington, DC,
ASM Press, 2007, pp 1762-1788.
Reference Values:
Negative
Clinical References: Hazen KC, Howell SA: Candida, Cryptococcus, and other Yeasts of Medical
Importance. In Manual of Clinical Microbiology. Ninth edition. Edited by PR Murray. Washington, DC,
ASM Press, 2007, pp 1762-1788
Reference Values:
Negative
Clinical References: Soave R, Johnson WD Jr: Cryptosporidium and Isospora belli. J Infect Dis
1988;157:225-229
Useful For: Evaluation and classification of chronic neutrophilia Aids in the diagnosis of chronic
neutrophilic leukemia (CNL) Mutation identification may suggest the class of kinase inhibitor to which
the neoplasm may be sensitive.
Interpretation: The results will be given as positive or negative for CSF3R mutation and, if positive,
the mutation will be described.
Reference Values:
An interpretive report will be provided
Clinical References: 1. Maxson JE, Gotlib J, Pollyea DA, et al: Oncogenic CSF3R mutations in
chronic neutrophilic leukemia and atypical CML. N Engl J Med 2013;368:1781-1790 2. Pardanani A,
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 630
Lasho TL, Laborde RR, et al: CSF3R T618I is a highly prevalent and specific mutation in chronic
neutrophilic leukemia. Leukemia 2013; 27,1870-1873 3. Tefferi A, Thiele J, Vannucchi AM, et al: An
overview on CALR and CSF3R mutations and a proposal for revision of WHO diagnostic criteria for
myeloproliferative neoplasms. Leukemia 2014;1:1-7 4. Vandenberghe P, Beel K: Severe congenital
neutropenia, a genetically heterogeneous disease group with an increased risk of AML/MDS. Pediatr Rep
2011;3(s2):e9
Interpretation: All detected alterations will be evaluated according to the American College of
Medical Genetics and Genomics (AMCG) recommendations.(1) Variants will be classified based on
known, predicted, or possible pathogenicity and reported with interpretive comments detailing their
potential or known significance.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for
standards for interpretation and reporting of sequence variations: Revisions 2007. Genet Med
2008;10(4):294-300 2. Teich N, Mossner J: Hereditary chronic pancreatitis. Best Pract Res Clin
Gastroenterol 2008;22(1):115-130 3. Solomon S, Whitcomb DC: Genetics of pancreatitis: an update for
clinicians and genetic counselors. Curr Gastroenterol Rep 2012;14(2):112-117 4. Ellis I: Genetic
counseling for hereditary pancreatitis-the role of molecular genetics testing for the cationic trypsinogen
gene, cystic fibrosis and serine protease inhibitor Kazal type 1. Gastroenterol Clin North Am
2004;33:839-854 5. LaRusch J, Solomon S, Whitcomb DC. Pancreatitis Overview. 2014 Mar 13. In:
Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews (Internet). Seattle (WA): University
of Washington, Seattle; 1993-2014. Available from: http://www.ncbi.nlm.nih.gov/books/NBK190101/
FCUIX CU Index
57549 Reference Values:
< 10.0
The CU Index test is the second generation Functional Anti-FceR test. Patient with a CU Index greater
than or equal to 10 have basophil reactive factors in their serum which supports an autoimmune basis
for disease.
The CU Index test is the second generation Functional Anti-FceR test. Patients with a CU Index
greater than or equal to 10 have basophil reactive factors in their serum which supports and autoimmune
basis for disease.
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical utility
of food-specific IgG tests has not been established. These tests can be used in special clinical situations to
select foods for evaluation by diet elimination and challenge in patients who have food-related
complaints. It should be recognized that the presence of food-specific IgG alone cannot be taken as
evidence of food allergy and only indicates immunologic sensitization by the food allergen in question.
This test should only be ordered by physicians who recognize the limitations of the test.
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
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5 50.0-99.9 Strongly positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 634
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Clinical References: Shea YR: General approaches for detection and identification of fungi. In
Manual of Clinical Microbiology. 10th edition. Edited by J Versalovic, KC Carroll, et al: Washington,
DC. ASM Press, 2011, pp 1776-1792
Useful For: Rapid identification to the species level for Mycobacterium species, Nocardia species, and
other aerobic actinomycete genera and species from pure culture isolates
Interpretation: Organisms growing in pure culture are identified to the species level whenever
possible.
Reference Values:
Not applicable
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
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0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 637
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Reference Values:
<0.35 kU/L
Useful For: Providing potentially prognostic information in patients with documented systemic
anaplastic lymphoma kinase-negative anaplastic large cell lymphoma
Interpretation: Systemic anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma
(ALCL) with rearrangements of DUSP22(IRF4) but without rearrangements of TP63 on 3q28 have been
associated with favorable clinical outcomes. Therefore, presence or absence of a TP63 rearrangement
needs to be determined to interpret this test accurately. The clinical significance of identifying this
rearrangement in cutaneous CD30-positive T-cell lymphoproliferative disorders, including primary
cutaneous ALCL and lymphomatoid papulosis, has not been established. Furthermore, other T- and
B-lineage neoplasms can demonstrate this finding. Clinical and pathologic correlation is recommended. A
neoplastic clone is detected when the percent of cells with an abnormality exceeds the normal cutoff for
the DUSP22(IRF4) probe set. A negative result suggests that an DUSP22(IRF4) gene rearrangement is
not present, but does not exclude the diagnosis of ALCL.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 638
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Feldman AL, Law M, Remstein ED, et al: Recurrent translocations
involving the IRF4 oncogene locus in peripheral T-cell lymphomas. Leukemia 2009;23:574-580 2.
Feldman AL, Dogan A, Smith DI, et al: Discovery of recurrent t(6;7)(p25.3;q32.3) translocations in
ALK-negative anaplastic large cell lymphomas by massively parallel genomic sequencing. Blood 2011
Jan 20;117(3):915-919 3. Parilla Castellar ER, Jaffe ES, Said JW, et al: ALK-negative anaplastic large
cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes. Blood
2014 Aug 28;124(9):1473-1480
Reference Values:
Report includes presence and titer of circulating antibodies. If serum contains BMZ antibodies on
split-skin substrate, patterns will be reported as: 1) epidermal pattern, consistent with pemphigoid or 2)
dermal pattern, consistent with epidermolysis bullosa acquisita.
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Useful For: Confirming a diagnosis of bullous pemphigoid, cicatricial pemphigoid, variants of
pemphigoid, all types of pemphigus, dermatitis herpetiformis, linear IgA bullous dermatosis, chronic
bullous disease of childhood, epidermolysis bullosa acquisita, porphyria cutanea tarda, bullous eruption of
lupus erythematosus, herpes gestationis, and atypical or mixed forms of bullous disease, systemic lupus
erythematosus, discoid lupus erythematosus, or other variants, vasculitis, lichen planus, and other
inflammatory diseases.
Interpretation: In pemphigus, direct immunofluorescence (IF) testing will show deposition of IgG, or
rarely IgA, and often complement C3 (C3) at the cell surface (intercelluar substances). In bullous
pemphigoid and cicatricial pemphigoid, direct IF study demonstrates deposition of IgG and C3 at the
basement membrane zone (BMZ) in a linear pattern. In cicatricial pemphigoid, a disease uncommonly
associated with circulating anti-BMZ antibodies, direct IF testing is particularly useful. Biopsy from
patients with dermatitis herpetiformis will show IgA concentrated in dermal papillae and/or in a granular
pattern at the BMZ. In lupus erythematosus (LE), there are granular deposits of immunoglobulin and
complement at the BMZ ("lupus band"). A lupus band is typically found in lesional skin from patients
with a variety of forms of LE; similar findings in biopsies of uninvolved "normal" skin are consistent with
systemic LE. Biopsy of early inflammatory purpuric lesions of vasculitis will show immunoglobulins
and/or complement in dermal vessels. The diagnostic value of direct IF testing is illustrated in the chart
Results of IF Testing under Cutaneous Immunofluorescence Testing in Special Instructions.
Reference Values:
Report includes description and interpretation of staining patterns. See Results of IF Testing in Cutaneous
Immunofluorescence Testing in Special Instructions.
Exposed:
Levels of less than 0.2 mg/L have been found to be non-toxic; however, levels of 0.5 to 1.0 mg/L have
been associated with tachycardia and flushing.
Toxic:
Levels of 1.0 to 2.5 mg/L have been associated with obtundation, coma and respiratory depression with
levels greater than 2.5 mg/L, and death with values greater than 3 mg/L.
Useful For: The differential diagnosis of hypercalcemia An adjunct to serum parathyroid hormone
measurements, especially in the diagnosis of parathyroid hormone resistance states, such as
pseudohypoparathyroidism
Interpretation: Urinary cyclic AMP is elevated in about 85% of patients with hyperparathyroidism
and in about 50% of patients with humoral hypercalcemia of malignancy.
Reference Values:
1.3-3.7 nmol/dL of glomerular filtrate
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Clinical References: Aurbach GD, Marx SJ, Spiegel AM: Parathyroid hormone, calcitonin, and
the calciferols. In Williams Textbook of Endocrinology. Eighth edition. Edited by JD Wilson, DW
Foster. Philadelphia, WB Saunders Company, 1992, pp 1413-1415
Useful For: Evaluating patients suspected of having rheumatoid arthritis (RA) Differentiating RA
from other connective tissue diseases that may present with arthritis
Interpretation: A positive result for cyclic citrullinated peptide (CCP) antibodies indicates a high
likelihood of rheumatoid arthritis (RA). A Mayo prospective clinical evaluation of the CCP antibody
test showed a diagnostic sensitivity for RA of 78% with fewer than 5% false positive results in healthy
controls (see Cautions). CCP antibodies have also been reported in approximately 40% of seronegative
RA patients, and, like rheumatoid factor (RF), a positive CCP antibody result indicates an increased
likelihood of erosive disease in patients with RA. High levels of CCP antibodies may be useful to
identify patients with aggressive disease, but further studies are needed to document this association.
The level of CCP antibodies may also correlate with disease activity in RA, but further studies are
needed to document this clinical application.
Reference Values:
<20.0 U (negative)
20.0-39.9 U (weak positive)
40.0-59.9 U (positive)
> or =60.0 U (strong positive)
Reference values apply to all ages.
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60859 Cyclin D1 (CCND1, CYCD1), Immunostain Without Interpretation
Clinical Information: Cyclin D1 is a protein that regulates entry of the cell into cell cycle. It drives
the transition between G0 and G1 phase. In normal tissues, basal epithelial cells, endothelial cells and
stromal cells are often cyclin D1 positive, as these cells are going through the cell cycle. As a result of a
translocation involving the cyclin D1 gene and IgH, t(11;14), the vast majority of mantle cell lymphomas
overexpress cyclin D1. This is a useful feature in the classification of low grade B-cell lymphomas.
Clinical References: 1. Cook JR, His ED, Worley S, et al: Immunohistochemical analysis identifies
two cyclin D1+ subsets of plasma cell myeloma, each associated with favorable survival. Am J Clin
Pathol 2006;125:615-624 2. Miranda RN, Briggs RC, Kinney MC, et al: Immunohistochemical detection
of cyclin D1 using optimized conditions is highly specific for mantle cell lymphoma and hairy cell
leukemia. Modern Pathology 2000;13(12):1308-1314 3. Vasef MA, Medeiros LJ, Koo C, et al: Cyclin D1
immunohistochemical staining is useful in distinguishing mantle cell lymphoma from other low-grade
B-cell neoplasms in bone marrow. Am J Clin Pathol 1997;108(3):302-307 4. Zukerberg LR, Yang WI,
Arnold A, Harris NL: Cyclin D1 expression in non-Hodgkins lymphomas. Detection by
Immunohistochemistry. Am J Clin Pathol 1995;103(6):756-760
Reference Values:
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 642
Negative
If positive, reported as Cyclospora cayetanensis detected.
Useful For: Monitoring whole blood cyclosporine concentration during therapy, particularly in
individuals coadministered CYP3A4 substrates, inhibitors, or inducers Adjusting dose to optimize
immunosuppression while minimizing toxicity Evaluating patient compliance
Interpretation: Most individuals display optimal response to cyclosporine with trough whole blood
levels 100 to 400 ng/mL. Preferred therapeutic ranges may vary by transplant type, protocol, and
comedications. Therapeutic ranges are based on specimens drawn at trough (ie, immediately before the
next scheduled dose). Blood drawn at other times will yield higher results. This test may also be used to
analyze cyclosporine levels 2 hours after dosing (C2 concentrations); trough therapeutic ranges do not
apply to C2 specimens. The assay is specific for cyclosporine; it does not cross-react with cyclosporine
metabolites, sirolimus, sirolimus metabolites, tacrolimus, or tacrolimus metabolites. Results by liquid
chromatography with detection by tandem mass spectrometry are approximately 30% less than by
immunoassay.
Reference Values:
100-400 ng/mL (Trough)
Target steady-state trough concentrations vary depending on the type of transplant, concomitant
immunosuppression, clinical/institutional protocols, and time post-transplant. Results should be
interpreted in conjunction with this clinical information and any physical signs/symptoms of
rejection/toxicity.
Clinical References: 1. Moyer TP, Post GR, Sterioff S, et al: Cyclosporine nephrotoxicity is
minimized by adjusting dosage on the basis of drug concentration in blood. Mayo Clin Proc 1988
March;63(3):241-247 2. Kahan BD, Keown P, Levy GA, et al: Therapeutic drug monitoring of
immunosuppressant drugs in clinical practice. Clin Ther 2002 March; 24(3):330-350 3. Dunn CJ,
Wagstaff AJ, Perry CM, et al: Cyclosporin: an updated review of the pharmacokinetic properties,
clinical efficacy, and tolerability of a microemulsion-based formulation (Neoral) 1 in organ
transplantation. Drugs 2001;61(13):1957-2016
Useful For: Monitoring whole blood cyclosporine concentration during therapy, particularly in
individuals coadministered CYP3A4 substrates, inhibitors, or inducers Adjusting dose to optimize
immunosuppression while minimizing toxicity Evaluating patient compliance
Interpretation: No definitive therapeutic or toxic ranges have been established for postdose peak
monitoring. Preferred therapeutic ranges may vary by transplant type, protocol, and comedications. The
2-hour postdose cyclosporine ranges listed for this test are only suggested guidelines. This assay is
specific for cyclosporine; it does not cross-react with cyclosporine metabolites, sirolimus, sirolimus
metabolites, tacrolimus, or tacrolimus metabolites. Results by liquid chromatography with detection by
tandem mass spectrometry are approximately 30% less than by immunoassay.
Reference Values:
No definitive therapeutic or toxic ranges have been established.
Optimal blood drug levels are influenced by type of transplant, patient response, time posttransplant,
coadministration of other drugs, and drug formulation.
The following 2-hour postdose cyclosporine ranges are only suggested guidelines:
Renal transplant: 800-1700 ng/mL
Liver transplant: 600-1000 ng/mL
Target steady-state peak concentrations vary depending on the type of transplant, concomitant
immunosuppression, clinical/institutional protocols, and time posttransplant. Results should be interpreted
in conjunction with this clinical information and any physical signs/symptoms of rejection/toxicity.
Clinical References: 1. Moyer TP, Post GR, Sterioff S, et al: Cyclosporine nephrotoxicity is
minimized by adjusting dosage on the basis of drug concentration in blood. Mayo Clin Proc 1988
March;63(3):241-247 2. Kahan BD, Keown P, Levy GA, et al: Therapeutic drug monitoring of
immunosuppressant drugs in clinical practice. Clin Ther 2002 March; 24(3):330-350 3. Dunn CJ,
Wagstaff AJ, Perry CM, et al: Cyclosporin: an updated review of the pharmacokinetic properties, clinical
efficacy, and tolerability of a microemulsion-based formulation (Neoral) 1 in organ transplantation. Drugs
2001;61(13):1957-2016
Useful For: An aid to optimizing treatment with tacrolimus and potentially other drugs metabolized
by CYP3A5
Interpretation: Absence of the *3 allele does not rule out the possibility that a patient harbors
another variant that can impact the function of this enzyme, drug response, or drug side effects.
CYP3A5 genotype is only one factor that should be taken into consideration for drug dosing.
CYP3A5*1/*1 Extensive (normal) metabolizer: The CYP3A5*3 allele was not detected. Therefore, this
patient is expected to be an extensive (normal) metabolizer. This phenotype is also known as CYP3A5
expresser. Rapid metabolism of drugs that are inactivated or activated by CYP3A5 is expected. Patients
with this phenotype should not be co-administered CYP3A5 inhibitors due to an increased risk of
toxicity or lack of efficacy, respectively. For patients taking tacrolimus with this genotype, the literature
indicates that higher doses may be required, presumably because original dosing guidelines were
determined on patients who were poor metabolizers. Therapeutic drug monitoring is recommended.
CYP3A5*1/*3 Intermediate metabolizer: One copy of the CYP3A5*3 allele was detected. Therefore,
this patient is expected to be an intermediate metabolizer. This phenotype is also known as CYP3A5
expresser. Reduced metabolism of drugs that are inactivated or activated by CYP3A5 is expected when
compared to patients who are *1/*1. Patients with this phenotype should not be coadministered
CYP3A5 inhibitors due to an increased risk of toxicity or lack of efficacy, respectively. For patients
taking tacrolimus with this genotype, the literature indicates that higher doses may be required,
presumably because original dosing guidelines were determined on patients who were poor
metabolizers. Therapeutic drug monitoring is recommended. CYP3A5*3/*3 Poor metabolizer: Two
copies of the CYP3A5*3 allele were detected. Therefore, this patient is expected to be a poor
metabolizer. This phenotype is also known as CYP3A5 nonexpresser. Drugs that are inactivated or
activated by CYP3A5 are metabolized at greatly reduced rate when compared to patients who are *1/*1.
Patients with this phenotype should not be coadministered CYP3A5 inhibitors due to an increased risk
of toxicity or lack of efficacy, respectively. For patients taking tacrolimus with this genotype, the
literature supports normal dosing, presumably because original dosing guidelines were determined on
patients who were poor metabolizers like this patient. Therapeutic drug monitoring is recommended.
For additional information regarding pharmacogenomic genes and their associated drugs, please see the
Pharmacogenomic Associations Tables in Special Instructions. This resource also includes information
regarding enzyme inhibitors and inducers, as well as potential alternate drug choices.
Reference Values:
An interpretive report will be provided.
Useful For: An aid to optimizing treatment with tacrolimus and potentially other drugs metabolized by
CYP3A5 Genotyping patients who prefer not to have venipuncture done
Interpretation: Absence of the *3 allele does not rule out the possibility that a patient harbors another
variant that can impact the function of this enzyme, drug response, or drug side effects. CYP3A5
genotype is only one factor that should be taken into consideration for drug dosing. CYP3A5*1/*1
Extensive (normal) metabolizer: The CYP3A5*3 allele was not detected. Therefore, this patient is
expected to be an extensive (normal) metabolizer. This phenotype is also known as CYP3A5 expresser.
Rapid metabolism of drugs that are inactivated or activated by CYP3A5 is expected. Patients with this
phenotype should not be coadministered CYP3A5 inhibitors due to an increased risk of toxicity or lack of
efficacy, respectively. For patients taking tacrolimus with this genotype, the literature indicates that higher
doses may be required, presumably because original dosing guidelines were determined on patients who
were poor metabolizers. Therapeutic drug monitoring is recommended. CYP3A5*1/*3 Intermediate
metabolizer: One copy of the CYP3A5*3 allele was detected. Therefore, this patient is expected to be an
intermediate metabolizer. This phenotype is also known as CYP3A5 expresser. Reduced metabolism of
drugs that are inactivated or activated by CYP3A5 is expected when compared to patients who are *1/*1.
Patients with this phenotype should not be coadministered CYP3A5 inhibitors due to an increased risk of
toxicity or lack of efficacy, respectively. For patients taking tacrolimus with this genotype, the literature
indicates that higher doses may be required, presumably because original dosing guidelines were
determined on patients who were poor metabolizers. Therapeutic drug monitoring is recommended.
CYP3A5*3/*3 Poor metabolizer: Two copies of the CYP3A5*3 allele were detected. Therefore, this
patient is expected to be a poor metabolizer. This phenotype is also known as CYP3A5 nonexpresser.
Drugs that are inactivated or activated by CYP3A5 are metabolized at greatly reduced rate when
compared to patients who are *1/*1. Patients with this phenotype should not be coadministered CYP3A5
inhibitors due to an increased risk of toxicity or lack of efficacy, respectively. For patients taking
tacrolimus with this genotype, the literature supports normal dosing, presumably because original dosing
guidelines were determined on patients who were poor metabolizers like this patient. Therapeutic drug
monitoring is recommended. For additional information regarding pharmacogenomic genes and their
associated drugs, please see the Pharmacogenomic Associations Tables in Special Instructions. This
resource also includes information regarding enzyme inhibitors and inducers, as well as potential alternate
drug choices.
Reference Values:
An interpretive report will be provided.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 646
Clinical References: 1. Birdwell K, Decker B, Barbrino J, et al: Clinical pharmacogenetics
implementation consortium (CPIC) guidelines for CYP3A5 genotype and tacrolimus dosing. Clin
Pharmaco Ther 2015:98(1):19-24 doi: 10.1002/cpt.113 2. Thervet E, Loriot MA, Barbier S, et al:
Optimization of initial tacrolimus dose using pharmacogenetic testing. Clin PharmacolTher
2010;87:721-726 3. Lamba J, Hebert J, Schuetz E, et al: PharmGKB summary: very important
pharmacogene information for CYP3A5. Pharmacogenet Genomics 2012 Jul; 22(7):555-558
Useful For: Cystatin C: An index of glomerular filtration rate, especially in patients where serum
creatinine may be misleading (eg, very obese, elderly, or malnourished patients) Assessing renal
function in patients suspected of having kidney disease Monitoring treatment response in patients with
kidney disease Estimated Glomerular Filtration Rate (eGFR): An index of GFR, especially in patients
where serum creatinine may be misleading (eg, very obese, elderly, or malnourished patients); for such
patients, use of CKD-EPI cystatin C equation is recommended to estimate GFR Assessing renal
function in patients suspected of having kidney disease Monitoring treatment response in patients with
kidney disease
Interpretation: Cystatin C: Cystatin C inversely correlates with the glomerular filtration rate (GFR),
that is elevated levels of cystatin C indicate decreased GFR. Cystatin C may provide more accurate
assessment of GFR for very obese, elderly, or malnourished patients than creatinine. Cystatin C
equation does not require patient ethnic data, and can be used for those patients with this information
unavailable. Due to immaturity of renal function, cystatin C levels are higher in neonates <3 months of
age.(2) Estimated Glomerular Filtration Rate (eGFR): Chronic kidney disease (CKD) is defined as the
presence of: persistent and usually progressive reduction in GFR (GFR <60 mL/min/1.73 m[2]) and/or
albuminuria (>30 mg of urinary albumin per gram of urinary creatinine), regardless of GFR. According
to the National Kidney Foundation Kidney Disease Outcome Quality Initiative (K/DOQI) classification,
among patients with CKD, irrespective of diagnosis, the stage of disease should be assigned based on
the level of kidney function: Stage Description GFR mL/min/BSA 1 Kidney damage with normal or
increased GFR 90 2 Kidney damage with mild decrease in GFR 60-89 3 Moderate decrease in GFR
30-59 4 Severe decrease in GFR 15-29 5 Kidney failure <15 (or dialysis)
Reference Values:
CYSTATIN C
Males:
0 days-22 years: no reference values established
23-29 years: 0.60-1.03 mg/L
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30-39 years: 0.64-1.12 mg/L
40-49 years: 0.68-1.22 mg/L
50-59 years: 0.72-1.32 mg/L
60-69 years: 0.77-1.42 mg/L
70-79 years: 0.82-1.52 mg/L
>79 years: no reference values established
Females:
0 days-22 years: no reference values established
23-29 years: 0.57-0.90 mg/L
30-39 years: 0.59-0.98 mg/L
40-49 years: 0.62-1.07 mg/L
50-59 years: 0.64-1.17 mg/L
60-69 years: 0.66-1.26 mg/L
70-80 years: 0.68-1.36 mg/L
81-86 years: 0.70-1.45 mg/L
>86 years: no reference values established
eGFR
>60 mL/min/BSA
eGFR will not be calculated for patients under 18 years.
Clinical References: 1. Inker LA, Schmid CH, Tighiouart H, et al: Estimating glomerular filtration
rate from serum creatinine and cystatin C. N Engl J Med 2012 Jul;367(1):20-29 2. Buehrig CK, Larson
TS, Bergert JH, et al: Cystatin C is superior to serum creatinine for the assessment of renal function. J Am
Soc Nephrol 2001;12:194A 3. Grubb AO: Cystatin C - properties and use as a diagnostic marker. Adv
Clin Chem 2000;35:63-99 4. Coll E, Botey A, Alvarez L, et al: Serum cystatin C as a new marker for
noninvasive estimation of glomerular filtration rate and as a marker for early renal impairment. Am J
Kidney Dis 2000 Jul;36(1):29-34 5. Flodin M, Jonsson AS, Hansson LO, et al: Evaluation of Gentian
cystatin C reagent on Abbott Ci8200 and calculation of glomerular filtration rate expressed in
mL/min/1.73 m(2) from the cystatin C values in mg/L. Scand J Clin Lab Invest 2007;67:560-567 6.
Larsson A, Hansson LO, Flodin M, et al: Calibration of the Siemens cystatin C immunoassay has changed
over time. Clin Chem 2011;57:777-778 7. Voskoboev NV, Larson TS, Rule AD, Lieske JC: Importance
of cystatin C assay standardization. Clin Chem 2011 Aug;57(8):1209-1211 8. Nitsch D, Sandling JK,
Byberg L et al: Fetal, developmental, and parental influences on cystatin C in childhood: the Uppsala
Family Study. Am J Kidney Dis 2011 Jun;57(6):863-872 9. Voskoboev NV, Larson TS, Rule AD, Lieske
JC: Analytic and clinical validation of a standardized cystatin C particle enhanced turbidimetric assay
(PETIA) to estimate glomerular filtration rate. Clin Chem Lab Med 2012 Mar;50(9):1591-1596 10.
Finney H, Newman DJ, Thakkar H, et al: Reference ranges for the plasma cystatin C and creatinine
measurements in premature infants, neonates, and older children. Arch Dis Child 2000 Jan;82(1):71-75
Useful For: Confirmation of a clinical diagnosis of cystic fibrosis Risk refinement via carrier
screening for individuals in the general population Prenatal diagnosis or familial mutation testing when
the familial mutations are included in the 106-mutation panel listed above (if familial mutations are not
included in the 106-mutation panel, order FMTT / Familial Mutation, Targeted Testing) Risk
refinement via carrier screening for individuals with a family history when familial mutations are not
available Identification of patients who may respond to CFTR potentiator therapy
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FCAI Cysticercosis Antibody, IgG by ELISA
75097 Interpretation: Seroconversion between acute and convalescent sera is considered strong evidence of
recent infection. The best evidence for infection is a significant change on two appropriately timed
specimens where both tests are done in the same laboratory at the same time. Patients with collagen
vascular diseases, hepatic cirrhosis, schistosomiasis, and other parasitic infections can produce
false-positive results. There is a strong cross-reaction between cysticercosis and echinococcosis positive
sera. Confirmation of positive ELISA results by the cysticercosis antibody, IgG by Western blot is
recommended.
Reference Values:
Reference Interval: <=0.34 O.D.
0.34 O.D. or less: Negative- No significant level of cysticercosis IgG antibody detected.
0.51 O.D. or greater: Positive- IgG antibody to cysticercosis detected, which may suggest current or past
infection.
Interpretive Criteria:
<0.75 Antibody Not Detected
> or = 0.75 Antibody Detected
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gene; type B, due to mutations in the SLC7A9 gene; and type AB, due to 1 mutation in each SLC3A1 and
SLC7A9.
Reference Values:
CYSTINE
3-15 years: 11-53 mcmol/24 hours
> or =16 years: 28-115 mcmol/24 hours
LYSINE
3-15 years: 19-140 mcmol/24 hours
> or =16 years: 32-290 mcmol/24 hours
ORNITHINE
3-15 years: 3-16 mcmol/24 hours
> or =16 years: 5-70 mcmol/24 hours
ARGININE
3-15 years: 10-25 mcmol/24 hours
> or =16 years: 13-64 mcmol/24 hours
Conversion Formulas:
Result in mcmol/24 hours x 0.24=result in mg/24 hours
Result in mg/24 hours x 4.17=result in mcmol/24 hours
Reference Values:
Urine Amino Acid Age Groups
Reference Values (nmol/mg
creatinine) < or =12 13-35 Months 3-6 Years 7-8 Years 9-17 Years > or =18 Years
Months
Ornithine Orn
Order MPCT / Muscle Pathology Consultation or MBCT / Muscle Biopsy Consultation, Outside Slides
and/or Paraffin Blocks. The consultant will determine the need for special stains.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 652
Enzyme Metabolism** *1 None (wild type) None (wild type) Extensive (normal) metabolizer *1K
-729C->T c.-10+113C->T Decreased activity and decreased inducibility *1F -163C->A c.-9-154C->A
Increased inducibility *4 2499A->T c.1156A->T Greatly reduced activity *5 3497G->A c.1217G->A
Decreased activity *6 5090C->T c.1291C->T No activity *7 3533G->A c.1253+1G->A No activity *8
5166G->A c.1367G->A No activity *11 558C->A c.558C->A No activity *15 125C->G c.125C->G No
activity *16 2473G->A c.1130G->A No activity **The frequency of these variants varies by ethnicity.
*Effect of a specific allele on the activity of the CYP1A2 enzyme can only be estimated since the
literature does not provide precise data. A complicating factor in correlating CYP1A2 genotype to
CYP1A2 phenotype is that some drugs or their metabolites are inhibitors of CYP1A2 catalytic activity.
These drugs may reduce CYP1A2 catalytic activity. Consequently, an individual may require a dose
decrease greater than predicted based upon genotype alone. Another complicating factor is that CYP1A2
is inducible by several drugs and environmental agents (eg, cigarette smoke) and the degree of
inducibility is under genetic control. It is important to interpret the results of testing in the context of other
coadministered drugs and environmental factors.
Useful For: Identifying individuals who are poor, intermediate, extensive, or ultrarapid metabolizers
of drugs metabolized by CYP1A2 to assist drug therapy decision making
Interpretation: An interpretive report will be provided that includes assay information, genotype,
and an interpretation indicating whether results are consistent with a poor, intermediate, extensive, or
ultrarapid metabolizer phenotype. The genotype, with associated star alleles, is assigned using standard
allelic nomenclature as published by the Human Cytochrome P450 (CYP) Allele Nomenclature
Database Committee.(1) CYP1A2 activity is also dependent upon hepatic function status, as well as
age. Renal function may be important for drugs that are also excreted in urine. Patients may develop
drug toxicity if hepatic or renal function is decreased. Drug metabolism is known to decrease with age.
It is important to interpret the results of testing and dose adjustments in the context of hepatic and renal
function and age. For additional information regarding pharmacogenomic genes and their associated
drugs, see Pharmacogenomic Associations Tables in Special Instructions. This resource also includes
information regarding enzyme inhibitors and inducers, as well as potential alternate drug choices.
Reference Values:
An interpretive report will be provided.
Useful For: Identifying individuals who are poor, intermediate, extensive, or ultrarapid metabolizers of
drugs metabolized by CYP1A2 to assist drug therapy decision making Genotyping patients who prefer not
to have venipuncture done
Interpretation: An interpretive report will be provided that includes assay information, genotype, and
an interpretation indicating whether results are consistent with a poor, intermediate, extensive, or
ultra-rapid metabolizer phenotype. The genotype, with associated star alleles, is assigned using standard
allelic nomenclature as published by the Human Cytochrome P450 (CYP) Allele Nomenclature Database
Committee.(1) CYP1A2 activity is also dependent upon hepatic function status, as well as age. Renal
function may be important for drugs that are also excreted in urine. Patients may develop drug toxicity if
hepatic or renal function is decreased. Drug metabolism is known to decrease with age. It is important to
interpret the results of testing and dose adjustments in the context of hepatic and renal function and age.
For additional information regarding pharmacogenomic genes and their associated drugs, see
Pharmacogenomic Associations Tables in Special Instructions. This resource also includes information
regarding enzyme inhibitors and inducers, as well as potential alternate drug choices.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Human Cytochrome P450 (CYP) Allele Nomenclature Database. Accessed
9/21/15. Available at: http://www.cypalleles.ki.se/cyp1a2.htm 2. Ito M, Katono Y, Oda A, et al:
Functional characterization of 20 allelic variants of CYP1A2. Drug Metab Pharmacokinet 2015
Jun;30(3):247-252 3. Zhou H, Josephy PD, Kim D, Guengerick FP: Functional characterization of four
allelic variants of human cytochrome P450 1A2. Arch Biochem Biophys 2004 Feb;422(1):23-30 4.
Murayama N, Soyama A, Saito Y, et al: Six novel nonsynonymous CYP1A2 gene polymorphisms:
catalytic activities of the naturally occurring variant enzymes. J Pharmacol Exp Ther 2004
Jan;308(1):300-306 5. Saito Y, Hanioka N, Maekawa K, et al: Functional analysis of three CYP1A2
variants found in a Japanese population. Drug Metab Dispos 2005 Dec;33(12):1905-1910
Useful For: Identifying patients who may be at risk for altered metabolism of drugs that are modified
by CYP2C19 Predicting anticoagulation response to clopidogrel
Interpretation: A report will be provided that includes CYP2C19 genotype, predicted CYP2C19
phenotype, and assay information. The genotype, with associated star alleles, is assigned using standard
allelic nomenclature as published by the Human Cytochrome P450 (CYP) Allele Nomenclature
Database Committee.(1) For additional information regarding pharmacogenomic genes and their
associated drugs, see the Pharmacogenomics Associations Tables in Special Instructions. This resource
also includes information regarding enzyme inhibitors and inducers, as well as potential alternate drug
choices. Drug-drug interactions and drug-metabolite inhibition must be considered when treating
intermediate metabolizers. It is important to interpret the results of testing and dose adjustments in the
context of hepatic and renal function and patient age.
Reference Values:
An interpretive report will be provided.
Useful For: Identifying patients who may be at risk for altered metabolism of drugs that are modified
by CYP2C19 Predicting anticoagulation response to clopidogrel Genotyping patients who prefer not to
have venipuncture done
Interpretation: A report will be provided that includes CYP2C19 genotype, predicted CYP2C19
phenotype, and assay information. The genotype, with associated star alleles, is assigned using standard
allelic nomenclature as published by the Human Cytochrome P450 (CYP) Allele Nomenclature Database
Committee.(1) For additional information regarding pharmacogenomic genes and their associated drugs,
see the Pharmacogenomics Associations Tables in Special Instructions. This resource also includes
information regarding enzyme inhibitors and inducers, as well as potential alternate drug choices.
Drug-drug interactions and drug-metabolite inhibition must be considered when treating intermediate
metabolizers. It is important to interpret the results of testing and dose adjustments in the context of
hepatic and renal function and patient age.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Human Cytochrome P450 (CYP) Allele Nomenclature Database. Accessed
Sept 21, 2015. Available from URL: http://www.cypalleles.ki.se/cyp1a2.htm 2. Blaisdell J, Mohrenweiser
H, Jackson J, et al: Identification and functional characterization of new potentially defective alleles of
human CYP2C19. Pharmacogenetics 2002 Dec;12(9):703-711 3. Hicks J, Bishop J, Sangkuhl K, et al:
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19
Genotypes and Dosing of Selective Serotonin Reuptake Inhibitors. Clin Pharmacol Ther
2015;98(2):127-34 4. Hicks J, Swen J, Thorn C, et al: Clinical Pharmacogenetics Implementation
Consortium guideline for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants. Clin
Pharmacol Ther 2013;93(5):402-408 5. Mega J, Close S, Wiviott D, et al: Cytochrome P-450
polymorphisms and response to clopidogrel. N Engl J Med 2009;360:354-362
Useful For: Identifying individuals who may be at risk for altered metabolism of drugs that are
modified by CYP2C9
Interpretation: A report will be provided that includes CYP2C9 genotype, predicted CYP2C9
phenotype, and assay information. The genotype, with associated star alleles, is assigned using standard
allelic nomenclature as published by the Human Cytochrome P450 (CYP) Allele Nomenclature
Database Committee.(1) Novel variants will be classified based on known, predicted, or possible effect
on gene function and reported with interpretive comments detailing their potential or known
significance. For additional information regarding pharmacogenomic genes and their associated drugs,
see the Pharmacogenomics Associations Tables in Special Instructions. This resource also includes
information regarding enzyme inhibitors and inducers, as well as potential alternate drug choices.
Drug-drug interactions and drug/metabolite inhibition must be considered in the case of intermediate
metabolism. It is important to interpret the results of testing and dose adjustments in the context of
hepatic and renal function and patient age.
Reference Values:
An interpretive report will be provided.
Useful For: Identifying individuals who may be at risk for altered metabolism of drugs that are
modified by CYP2C9 Genotyping patients who prefer not to have venipuncture done
Interpretation: A report will be provided that includes CYP2C9 genotype, predicted CYP2C9
phenotype, and assay information. The genotype, with associated star alleles, is assigned using standard
allelic nomenclature as published by the Human Cytochrome P450 (CYP) Allele Nomenclature Database
Committee.(1) Novel variants will be classified based on known, predicted, or possible effect on gene
function and reported with interpretive comments detailing their potential or known significance. For
additional information regarding pharmacogenomic genes and their associated drugs, see the
Pharmacogenomics Associations Tables in Special Instructions. This resource also includes information
regarding enzyme inhibitors and inducers, as well as potential alternate drug choices. Drug-drug
interactions and drug-metabolite inhibition must be considered in the case of intermediate metabolism. It
is important to interpret the results of testing and dose adjustments in the context of hepatic and renal
function and patient age.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Human Cytochrome P450 (CYP) Allele Nomenclature Database. Accessed
9/21/15. Available at: http://www.cypalleles.ki.se/cyp1a2.htm/ 2. Caudle KE, Rettie AE, Whirl-Carrillo
M, et al: Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and HLA-B
genotypes and phenytoin dosing. Clin Pharmacol Ther 2014;96(5):542-548 3. Niemi M, Cascorbi I, Timm
R, et al: Glyburide and glimepiride pharmacokinetics in subjects with different CYP2C9 genotypes. Clin
Pharmacol Ther 2002;72:326-332 4. Johnson JA, Gong L, Whirl-Carrillo M, et al: Clinical
Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and VKORC1 genotypes and
warfarin dosing. Clin Pharmacol Ther 2011;90(4):625-629 5. Blaisdell J, Jorge-Nebert LF, Coulter S, et
al: Discovery of new potentially defective alleles of human CYP2C9. Pharmacogenetics
2004;14(8):527-537
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 658
Negligible activity *36 No or null activity *3, *4, *4N, *5, *6, *7, *8, *11, *12, *13, *14A, *15, *68
CYP2D6 phenotype is predicted based upon the number of functional, partially functional, and
nonfunctional alleles present in a sample. (see Table 2) Table 2. Phenotype Assignment of CYP2D6
Predicted Drug Metabolizer Phenotype** Without Gene Duplication With Gene Duplication UM 2
increased activity alleles 3 normal and/or increased activity alleles EM to UM A combination of 1 normal
activity allele with 1 increased activity allele A combination of 2 normal alleles with one decreased
activity allele EM 2 normal activity alleles; a combination of one increased activity allele with one
decreased allele A combination of 2 normal alleles with 1 null allele; a combinantion of 1 normal allele
with 2 decreased activity alleles IM to EM A combination of 1 normal activity allele with 1 decreased
activity allele; a combination of 1 increased activity with 1 null allele 1 increased activity allele with 2
null alleles, 3 decreased activity alleles IM 1 normal activity allele with 1 null activity allele; 2 decreased
activity alleles 1 normal allele with 2 or more null alleles, 2 decreased activity alleles with 1 null allele.
PM to IM A combination of 1 decreased activity allele with 1 null allele 1 decreased activity allele with 2
null allele PM Only null alleles detected * Phenotyping was derived from the Human Cytochrome P450
(CYP) Allele Nomenclature Committee website and the PharmGKB website for the related Clinical
Pharmacogenetics Implementation Consortium guidelines. **Ultra-Rapid Metabolizer, UM; Extensive
Metabolizer, EM; Intermediate Metabolizer, IM; Poor Metabolizer, PM There are instances where a
phenotype prediction is not categorical and, in these instances, a range of possible phenotypes will be
given. It should be noted that other laboratories may use different phenotype prediction methods as there
is no consensus on this at this time. However, the method used here represents the findings of the majority
of literature available at this time. Individuals without a detectable gene alteration will have the predicted
phenotype of an extensive drug metabolizer and are designated as CYP2D6 *1/*1. Dosing drugs that are
metabolized through CYP2D6 may require adjustment based on the individual patient's genotype. Patients
who are poor metabolizers may require lower than usual doses to achieve optimal response in the case of
drugs that are inactivated by the CYP2D6 enzyme and higher than usual doses in the case of drugs that are
activated by CYP2D6 enzyme. Alternatively, patients who are ultrarapid metabolizers may benefit from
increased doses in the case of drugs that are inactivated by CYP2D6 enzyme and lower doses in the case
of drugs that are activated by CYP2D6. In the absence of clear guidance from FDA on dosing for various
metabolizer phenotypes, patients with either ultrarapid or poor metabolism may benefit by switching to
another comparable drugs that is not primarily metabolized by CYP2D6 or by therapeutic drug
monitoring where applicable. Overall, this test provides a comprehensive CYP2D6 genotype result for
patients, ensuring a more accurate phenotype prediction. This assay has clinical significance for patients
taking or considering medications activated (eg, codeine, tramadol, and tamoxifen) or inactivated (eg,
antidepressants and antipsychotics) by the CYP2D6 enzyme. The different tiers associated with the
CYP2D6 Cascade will be sequentially initiated until a complete genotype is determined.
Useful For: Providing information relevant to tamoxifen codeine, and tramadol, as well as other
medications metabolized by CYP2D6 Determining the exact genotype when other methods fail to
generate this information or if genotype-phenotype discord is encountered clinically Identifying exact
genotyping when required (eg, drug trials, research protocols) Identifying novel variants that may
interfere with drug metabolism
Interpretation: A comprehensive interpretive report will be provided that combines the results of all
tier testing utilized to obtain the final genotype. The genotype, with associated star alleles, is assigned
using standard allelic nomenclature as published by the Human Cytochrome P450 (CYP) Allele
Nomenclature Database Committee.(1) For the CYP2D6 Copy Number Variation assay, the reportable
copy number range is 0 to 4 copies for each of the CYP2D6 region assessed. Novel variants will be
classified based on known, predicted, or possible effect on gene function and reported with interpretive
comments detailing their potential or known significance. For additional information regarding
pharmacogenomic genes and their associated drugs, please see the Pharmacogenomics Associations
Tables in Special Instructions. This resource also includes information regarding enzyme inhibitors and
inducers, as well as potential alternate drug choices.
Reference Values:
A comprehensive interpretive report will be provided.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 660
may require lower than usual doses to achieve optimal response in the case of drugs that are inactivated
by the CYP2D6 enzyme, and higher than usual doses in the case of drugs that are activated by CYP2D6
enzyme. Alternatively, patients who are ultrarapid metabolizers may benefit from increased doses in the
case of drugs that are inactivated by CYP2D6 enzyme, and lower doses in the case of drugs that are
activated by CYP2D6. In the absence of clear guidance from FDA on dosing for various metabolizer
phenotypes, patients with either ultrarapid or poor metabolism may benefit from therapeutic drug
monitoring or switching to another comparable drug that is not primarily metabolized by CYP2D6.
Useful For: Determining the CYP2D6 genotype of patients considered for treatment with tamoxifen,
codeine, and tramadol, as well as other medications metabolized by CYP2D6 Genotyping patients who
prefer not to have venipuncture done
Interpretation: An interpretive report will be provided. All alterations detected will be reported with
standard allelic nomenclature as published by the Human Cytochrome P450 (CYP) Allele
Nomenclature Database Committee (http://www.cypalleles.ki.se/CYP2D6.htm). Novel variants will be
classified based on known, predicted, or possible effect on gene function and reported with interpretive
comments detailing their potential or known significance. For additional information regarding
pharmacogenomic genes and their associated drugs, please see the Pharmacogenomics Associations
Tables in Special Instructions. This resource also includes information regarding enzyme inhibitors and
inducers, as well as potential alternate drug choices.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for
standards for interpretation and reporting of sequence variations: Revisions 2007. Genet Med
2008:10(4):294-300 2. Human Cytochrome P450 (CYP) Allele Nomenclature Database. Accessed
September 21, 2015. Available at URL: http://www.cypalleles.ki.se/cyp2d6.htm 3. Black JL 3rd,
Walker DL, O'Kane DJ, Harmandayan M: Frequency of undetected CYP2D6 hybrid genes in clinical
samples: impact on phenotype prediction. Drug Metab Dispos 2012;40(1):111-119 4. Goetz MP, Rae
JM, Suman VJ, et al: Pharmacogenetics of tamoxifen biotransformation is associated with clinical
outcomes of efficacy and hot flashes. J Clin Oncol 2005;23:9312-9318 5. Kirchheiner J, Nickchen K,
Bauer M, et al: Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic
variations to the phenotype of drug response. Mol Psychiatry 2004;9:442-473 6. Crews KR, Gaedigk A,
Dunnenberger HM, et al: Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for
codeine therapy in the context of cytochrome P450 2D6 (CYP2D6) genotype. Clin Pharmacol Ther
2012 Feb;91(2):321-326 7. Hicks JK, Swen JJ, Thorn CF, et al: Clinical Pharmacogenetics
Implementation Consortium guideline for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic
antidepressants. Clin Pharmacol Ther 2013 May:93(5):402-408
Useful For: Aids in determining therapeutic strategies for drugs that are metabolized by CYP3A4,
including atorvastatin, simvastatin, and lovastatin
Interpretation: Extensive metabolizer: The CYP3A4*22 allele was not detected. Therefore, this
patient is expected to be an extensive metabolizer. Rapid metabolism of drugs that are inactivated or
activated by CYP3A4 is expected. Coadministration of CYP3A4 inhibitors may increase the risk of
toxicity for drugs inactivated by CYP3A4, or may cause lack of efficacy for drugs activated by CYP3A4.
Intermediate to extensive metabolizer: One copy of the CYP3A4*22 allele was detected. Therefore, this
patient is expected to be an intermediate to extensive metabolizer. Reduced metabolism of drugs that are
inactivated or activated by CYP3A4 is expected when compared to patients who are *1/*1.
Coadministration of CYP3A4 inhibitors may increase the risk of toxicity for drugs inactivated by
CYP3A4, or may cause lack of efficacy for drugs activated by CYP3A4. Intermediate metabolizer: Two
copies of the CYP3A4*22 allele were detected. Therefore, this patient is expected to be an intermediate
metabolizer. Drugs that are inactivated or activated by CYP3A4 are metabolized at reduced rate when
compared to patients who are *1/*1. Coadministration of CYP3A4 inhibitors may increase the risk of
toxicity for drugs inactivated by CYP3A4, or may cause lack of efficacy for drugs activated by CYP3A4.
Absence of the *22 allele does not rule out the possibility that a patient harbors another variant that can
impact the function of this enzyme, drug response, or drug side effects. The CYP3A4 genotype is only
one factor that should be taken into consideration for drug dosing. For additional information regarding
pharmacogenomic genes and their associated drugs, please see the Pharmacogenomics Associations
Tables in Special Instructions. This resource also includes information regarding enzyme inhibitors and
inducers, as well as potential alternate drug choices.
Reference Values:
An interpretive report will be provided.
Useful For: Aids in determining therapeutic strategies for drugs that are metabolized by CYP3A4,
including atorvastatin, simvastatin and lovastatin Genotyping patients who prefer not to have
venipuncture done
Interpretation: Extensive metabolizer: The CYP3A4*22 allele was not detected. Therefore, this
patient is expected to be an extensive metabolizer. Rapid metabolism of drugs that are inactivated or
activated by CYP3A4 is expected. Coadministration of CYP3A4 inhibitors may increase the risk of
toxicity for drugs inactivated by CYP3A4, or may cause lack of efficacy for drugs activated by
CYP3A4. Intermediate to extensive metabolizer: One copy of the CYP3A4*22 allele was detected.
Therefore, this patient is expected to be an intermediate to extensive metabolizer. Reduced metabolism
of drugs that are inactivated or activated by CYP3A4 is expected when compared to patients who are
*1/*1. Coadministration of CYP3A4 inhibitors may increase the risk of toxicity for drugs inactivated by
CYP3A4, or may cause lack of efficacy for drugs activated by CYP3A4. Intermediate metabolizer: Two
copies of the CYP3A4*22 allele were detected. Therefore, this patient is expected to be an intermediate
metabolizer. Drugs that are inactivated or activated by CYP3A4 are metabolized at reduced rate when
compared to patients who are *1/*1. Coadministration of CYP3A4 inhibitors may increase the risk of
toxicity for drugs inactivated by CYP3A4, or may cause lack of efficacy for drugs activated by
CYP3A4. Absence of the *22 allele does not rule out the possibility that a patient harbors another
variant that can impact the function of this enzyme, drug response, or drug side effects. The CYP3A4
genotype is only one factor that should be taken into consideration for drug dosing. For additional
information regarding pharmacogenomic genes and their associated drugs, please see the
Pharmacogenomics Associations Tables in Special Instructions. This resource also includes information
regarding enzyme inhibitors and inducers, as well as potential alternate drug choices.
Reference Values:
An interpretive report will be provided.
Reference Values:
Tumor Necrosis Factor alpha
Interleukin 2
Interleukin 12
Interferon gamma
Interleukin 4
Interleukin 5
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Interleukin 10
Interleukin 13
Interleukin 17
Interleukin 1 beta
Interleukin 6
Interleukin 8
Useful For: Determining whether a patient (especially transplant recipients, organ and blood donors)
has had a recent infection or previous exposure to cytomegalovirus
Interpretation: Positive cytomegalovirus (CMV) IgG results indicate past or recent CMV infection.
These individuals may transmit CMV to susceptible individuals through blood and tissue products.
Equivocal CMV IgG results may occur during acute infection or may be due to nonspecific binding
reactions. Submit an additional sample for testing if clinically indicated. Individuals with negative CMV
IgG results are presumed to not have had prior exposure or infection with CMV, and are therefore
considered susceptible to primary infection.
Reference Values:
Negative (reported as positive, negative, or equivocal)
Useful For: Diagnosis of primary, acute phase infection with cytomegalovirus (CMV), especially in
patients with infectious mononucleosis and pregnant women who, based on clinical signs or exposure,
may have primary CMV infection Determining whether a patient (especially transplant recipients, organ
and blood donors) has had a recent infection or previous exposure to CMV
Interpretation: IgM: A negative cytomegalovirus (CMV) IgM results suggest that the patient is not
experiencing a recent infection. However, a negative result does not rule out primary CMV infection. It
has been reported that CMV-specific IgM antibodies were not detectable in 10% to 30% of cord blood
sera from infants demonstrating infection in the first week of life. In addition, up to 23% (3/13) of
pregnant women with primary CMV infection did not demonstrate detectable CMV IgM responses
within 8 weeks post-infection. In cases of primary infection where the time of seroconversion is not
well defined as high as 28% (10/36) of pregnant women did not demonstrate CMV IgM antibody.
Positive CMV IgM results indicate a recent infection (primary, reactivation, or reinfection). IgM
antibody responses in secondary (reactivation) CMV infections have been demonstrated in some CMV
mononucleosis patients, in a few pregnant women, and in renal and cardiac transplant patients. Levels
of antibody may be lower in transplant patients with secondary rather than primary infections. IgG:
Positive CMV IgG results indicate past or recent CMV infection. These individuals may transmit CMV
to susceptible individuals through blood and tissue products. Individuals with negative CMV IgG results
are presumed to not have had prior exposure or infection with CMV, and are therefore considered
susceptible to primary infection. Equivocal CMV IgM or IgG results may occur during acute infection
or may be due to non-specific binding reactions. Submit an additional sample for testing if clinically
indicated.
Reference Values:
CMV IgM:
Negative (reported as positive, negative, or equivocal)
CMV IgG:
Negative (reported as positive, negative, or equivocal)
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Useful For: Diagnosis of primary, acute phase infection with cytomegalovirus (CMV), especially in
patients with infectious mononucleosis and pregnant women who, based on clinical signs or exposure,
may have primary CMV infection
Interpretation: A negative cytomegalovirus (CMV) IgM results suggest that the patient is not
experiencing a recent infection. However, a negative result does not rule-out primary CMV infection. It
has been reported that CMV-specific IgM antibodies were not detectable in 10% to 30% of cord blood
sera from infants demonstrating infection in the first week of life. In addition, up to 23% (3/13) of
pregnant women with primary CMV infection did not demonstrate detectable CMV IgM responses within
8 weeks postinfection. In cases of primary infection where the time of seroconversion is not well defined
as high as 28% (10/36) of pregnant women did not demonstrate CMV-IgM antibody. Positive CMV IgM
results indicate a recent infection (primary, reactivation, or reinfection). IgM antibody responses in
secondary (reactivation) CMV infections have been demonstrated in some CMV mononucleosis patients,
in a few pregnant women, and in renal and cardiac transplant patients. Levels of antibody may be lower in
transplant patients with secondary, rather than primary, infections. Equivocal CMV IgM results may
occur during acute infection or may be due to nonspecific binding reactions. Submit an additional sample
for testing if clinically indicated.
Reference Values:
Negative (Reported as positive, negative, or equivocal)
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(IFN-gamma), tumor necrosis factor alpha (TNF-alpha), macrophage inflammatory protein 1 alpha
(MIP-1 alpha), macrophage inflammatory protein 1 beta (MIP-1 beta), and interleukin-2 (IL-2). Several
studies have shown the importance of cytotoxic T-cell responses to CMV in conferring protection from
subsequent CMV disease. Antiviral drugs have helped reduce the incidence of early CMV infection, and
acyclovir and ganciclovir have been the mainstay of antiviral treatment for a number of years, although
these drugs have poor bioavailability.(4) The development of the new antiviral drugs valacyclovir and
valganciclovir (by the addition of a valine ester) has increased the bioavailability of these drugs by
10-fold.(4) There is some data to suggest valganciclovir prophylaxis may be considered for HSCT
patients who are at high risk for infection and disease, though there is a need for further study in this
area.(5) Two main strategies have been used for the prevention of early CMV infection and disease in
CMV-seropositive patients and in seronegative recipients who receive a seropositive graft-preemptive
therapy: -Patient monitoring for CMV infection and treatment only when CMV viremia is present.
-Prophylactic management-where all patients receive treatment after transplantation with the goal of
preventing CMV disease.(5) The disadvantage of prophylactic therapy is that it requires monitoring for
myelosuppression and infections-side effects of antiviral drug therapy. Despite this disadvantage, there
are several reasons to consider prophylaxis, including the fact that the incidence of recurrent infections
after treatment is 30% to 40%,(5) patients receiving preemptive therapy have a 5% CMV disease
break-through, and prophylaxis reduces the risk of viral reactivation. Late CMV infection occurs 3
months after transplantation and is now recognized as a significant cause of morbidity after allogeneic
HSCT. These complications usually occur in the setting of continued immunosuppression for chronic
graft-versus-host disease (GVHD). The clinical manifestations of late CMV disease differ slightly from
those seen early after transplantation. Within the first 100 days after HSCT, almost all patients with CMV
disease have CMV pneumonia or gastrointestinal disease. In late CMV disease, the more unusual
manifestations of CMV infection (eg, CMV retinitis, CMV-associated bone marrow failure, or CMV
encephalitis) tend to occur.(6) These late manifestations occur in a setting of continued CMV-specific
T-cell immunodeficiency. Therefore, it is necessary to monitor CMV-specific CD8 T-cell responses, in
addition to viral load, to effectively identify patients at higher risk of CMV disease. It has been shown that
ganciclovir may delay the recovery of the protective CMV-specific T-cell response, which may contribute
to the occurrence of late CMV disease.(7) The use of ganciclovir as early treatment after detection of
CMV in blood or other body fluid and as a prophylaxis for CMV infection in bone marrow transplant
(BMT) and heart transplant recipients has dramatically reduced the incidence of CMV in these
immunocompromised hosts. Yet, early treatment and prophylaxis have not been uniformly successful,
with up to 15% of BMT recipients developing CMV disease after discontinuation of antiviral therapy.
Similarly, patients undergoing lung transplantation have been shown to be only transiently protected with
antiviral agents. These data suggest that the CMV-specific responses necessary for protection may not
recover during the time the host is receiving antiviral therapy. Ganciclovir exerts its antiviral effects at the
stage of viral DNA replication and, therefore, in the presence of the drug, infected cells may express some
of the immediate early and early gene products, but not the full complement of CMV genes required for
replication and virion formation. In latently infected CMV-seropositive individuals, the HLA class
I-restricted cytotoxic T lymphocyte response to CMV is predominantly specific for epitopes derived from
structural virion proteins. Therefore, in patients receiving ganciclovir, the viral antigens may be
inadequate to activate host T-cell responses, resulting in the failure to reconstitute CMV-specific
immunity. In fact, a prospective, randomized placebo-controlled study of ganciclovir prophylaxis revealed
that when ganciclovir therapy is discontinued, a larger fraction of patients (who received the drug) are
deficient in CMV-specific T-cell immunity at day 100 than in the placebo group.(7) That study also
showed that bone marrow donor serology has an important influence on the early detection of
virus-specific T-cell responses.(7) Not all medical centers use ganciclovir for prophylaxis; some use
acyclovir and the same findings may apply in this case as well. In a more recent study, it was shown that
impaired CD8 function was associated with the use of high-dose steroids, bone marrow as a source of
stem cells, and CD8 T-cell lymphopenia.(3) In the absence of high-dose steroids, low-level subclinical
CMV antigenemia was found to stimulate both CD4 and CD8 functional recovery in recipients of
ganciclovir prophylaxis, suggesting that subclinical CMV reactivation while on antiviral therapy can be a
potent stimulator of T-cell function.(3) Regardless of antiviral therapy, immunologic reconstitution
remains the key element in protection from late-onset CMV disease. This test assesses the number of
CMV-specific CD8 T cells and their function (activation via production of the cytokine IFN-gamma and
cytotoxic potential via CD107a and CD107b as markers of degranulation) using a panel of 5 major
histocompatibility complex (MHC) class I alleles (HLA A1, A2, B7, B8, and B35) along with their
respective immunodominant CMV epitopes. This 3-part assay allows a comprehensive assessment of
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CMV-specific CD8 T cell immunity and, when combined with evaluation of viremia using molecular
analyses, provides a more accurate picture of the nature of CMV reactivation and the corresponding
immune response than evaluating viremia alone. Assessment of Global CD8 T-Cell Function: CD8 T cell
activation occurs either through the TCR-peptide-MHC or by use of a mitogen (eg, phorbol myristate
acetate and the calcium ionophore ionomycin). Mitogen-mediated activation is antigen nonspecific.
Impairment of global CD8 T cell activation (due to inherent cellular immunodeficiency or as a
consequence over immunosuppression by therapeutic agents) results in reduced production of IFN-gamma
and other cytokines, reduced cytotoxic function, and increased risk for developing infectious
complications. Agents associated with over-immunosuppression include the calcineurin inhibitors (eg,
cyclosporine A, FK506 [Prograf/tacrolimus], and rapamycin [sirolimus]), antimetabolites (eg,
mycophenolate mofetil), and thymoglobulin. The incorporation of global CD8 T cell function in this assay
is helpful in determining if the lack of CMV-specific (antigen-specific) response is due to a global
impairment in CD8 T cell function, due to immunosuppression or other causes, or whether the lack of
CMV CD8 T cell immunity is unrelated to overall CD8 T cell function. The absolute counts of
lymphocyte subsets are known to be influenced by a variety of biological factors, including hormones, the
environment, and temperature. The studies on diurnal (circadian) variation in lymphocyte counts have
demonstrated progressive increase in CD4 T-cell count throughout the day, while CD8 T cells and CD19+
B cells increase between 8:30 a.m. and noon, with no change between noon and afternoon. Natural killer
cell counts, on the other hand, are constant throughout the day.(8) Circadian variations in circulating
T-cell counts have been shown to be negatively correlated with plasma cortisol concentration.(9-11) In
fact, cortisol and catecholamine concentrations control distribution and, therefore, numbers of naive
versus effector CD4 and CD8 T cells.(9) It is generally accepted that lower CD4 T-cell counts are seen in
the morning compared with the evening (12), and during summer compared to winter.(13) These data,
therefore, indicate that timing and consistency in timing of blood collection is critical when serially
monitoring patients for lymphocyte subsets.
Interpretation: For allogeneic hematopoietic stem cell transplantation (HSCT) and solid organ
transplant patients who are cytomegalovirus (CMV)-seropositive and at risk for CMV reactivation,
posttransplant results should be compared to pretransplant (preconditioning/baseline) results. The report
includes absolute CD3 and CD8 T-cell counts as well as a derived CMV-specific CD8 T-cell count
(derived from CD3 and CD8 T-cell counts). The absolute count of CMV-CD8 T cells that are activated
and have cytotoxic function in response to specific CMV peptide is also provided. The data from the 3
components of this assay should be interpreted together and not individually. In the setting of CMV
viremia, frequent monitoring of CMV-immune competence helps define the evolution of the
CMV-immune response. In this clinical context, CMV-immune competence should be measured as
frequently as viral load to determine correlation between the 2 parameters. CMV-specific CD8 T-cell
counts may show a decline in numbers over time in the absence of active infection or antigenemia. The
absence of CMV-specific CD8 T cells may be a risk factor in the immune-compromised or
immune-incompetent transplant patient, who is at risk for CMV reactivation. The presence of
CMV-specific CD8 T cells may not be protective in itself. If the CMV-specific CD8 T cells do not show
appropriate cytotoxic function (due to the fact that they recognize CMV epitopes that do not effectively
induce a cytotoxic response), these patients may be at higher risk of an inadequate immune response to
CMV infection. While the reference values provide a guideline of CMV-specific CD8 T-cell numbers and
function in a cohort of healthy individuals, baseline (pretransplant/preconditioning) assessments should be
taken into consideration when determining CMV-specific immune competence posttransplant. Correlation
between data from multiple post-transplant specimens (if available) and the presence or absence of
viremia (or active CMV disease) also are useful in the interpretation of results. CD8 T cell counts are
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elevated when the immune system is initially reconstituted post-HSCT, and the CD4 to CD8 ratio can be
inverted for about 12 months post-HSCT. Interferon-gamma (IFN-gamma) and CD107a/b expression
below the defined reference range are consistent with a global impairment in CD8 T cell function, most
likely due to over-immunosuppression. IFN-gamma and CD107a/b levels greater than the defined
reference range are unlikely to have any clinical significance.
Reference Values:
Total CD3 T cells: 884-5,830 x 10(3)/mL
Total CD8 T cells: 168-1,847 x 10(3)/mL
Total CMV CD8 T cells: 0-115 x 10(3)/mL
The adult reference values were determined for healthy adult controls ages 20 to 80 years (n=94), for
HLA A1, A2, B7, B8, and B35 alleles.
Reference values for CMV-specific T cells that are functional (interferon-gamma+, IFN-g+) and have
cytotoxic activity (CD107a and CD107b expression, CD107 a/b+):
Total CMV CD8 T-cells IFN-g: 0.028-52.200 x 10(3)/mL
Total CMV CD8 T-cells CD107a/b: 0.252-50.760 x 10(3)/mL
The 95% confidence interval reference values were determined from 102 healthy adult donors:
Interferon-gamma (IFN-gamma) expression (as % CD8 T cells): 10.3-56.0%
CD107a/b expression (as % CD8 T cells): 8.5-49.1%
The reference values were developed for each of the following 4 major histocompatibility complex
class I alleles: A1, A2, B7, and B8 (n=45). We were unable to develop ranges for the B35 allele due to a
lack of matching donors. The data is expressed as the absolute number of CMV-specific CD8 T cells
that are IFN-gamma+ or CD107a/b+.
Clinical References: 1. Melnick JL, Adam E, Debakey ME: Cytomegalovirus and atherosclerosis.
Eur Heart J 1993;14:30-38 2. von Willebrand E, Petterson E, Ahnonen J, et al: CMV infection, class II
antigen expression, and human kidney allograft rejection. Transplantation 1986;42:364-367 3. Hakki M,
Riddell SR, Storek J, et al: Immune reconstitution to CMV after allogeneic hematopoietic stem cell
transplantation: impact of host factors, drug therapy, and subclinical reactivation. Blood
2003;102:3060-3067 4. Baden LR: Pharmacokinetics of valganciclovir in HSCT patients with
gastrointestinal GVHD. Biol Blood Marrow Transplant 2005;15(2):5-7 5. Bachier CR: Prevention of
early CMV infection in HSCT. Biol Blood Marrow Transplant 2005;15(2):8-9 6. Boeckh M: Prevention
of late CMV infection in HSCT. Biol Blood Marrow Transplant 2005;15(2):9-11 7. Li CR, Greenberg
PD, Gilbert MJ, et al: Recovery of HLA-restricted CMV-specific T cell responses after allogeneic bone
marrow transplant: correlation with CMV disease and effect of ganciclovir prophylaxis. Blood
1994;83(7):1971-1979 8. Carmichael KF, Abayomi A: Analysis of diurnal variation of lymphocyte
subsets in healthy subjects and its implication in HIV monitoring and treatment.15th Intl Conference on
AIDS, Bangkok, Thailand, 2004, Abstract B11052 9. Dimitrov S, Benedict C, Heutling D, et al:
Cortisol and epinephrine control opposing circadian rhythms in T-cell subsets. Blood
2009;113:5134-5143 10. Dimitrov S, Lange T, Nohroudi K, Born J: Number and function of circulating
antigen presenting cells regulated by sleep. Sleep 2007;30:401-411 11. Kronfol Z, Nair M, Zhang Q, et
al: Circadian immune measures in healthy volunteers: relationship to hypothalamic-pituitary-adrenal
axis hormones and sympathetic neurotransmitters. Pyschosomatic Medicine 1997;59:42-50 12. Malone
JL, Simms TE, Gray GC, et al: Sources of variability in repeated T-helper lymphocyte counts from HIV
1-infected patients: total lymphocyte count fluctuations and diurnal cycle are important. J AIDS
1990;3:144-151 13. Paglieroni TG, Holland PV: Circannual variation in lymphocyte subsets, revisited.
Transfusion 1994;34:512-516
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FCMIG Cytomegalovirus (CMV) IgG Avidity (AviDx), ELISA
75226 Clinical Information: Discrimination between recent (primary) and past cytomegalovirus (CMV)
infection can be an important tool in the clinical management of transplant recipients and pregnant
women. Although nearly all individuals with recent CMV infection are positive for CMV IgM,
individuals with past CMV may also express CMV IgM following viral reactivation; thus, detection of
CMV IgM is not a reliable indicator of recent CMV infection. Measurement of CMV IgG avidity can
assist in discriminating recent from past CMV infection. Although a low avidity index is a reliable
indicator of CMV infection within the previous 6 months, a high avidity index is more meaningful from a
clinical standpoint; a high avidity index essentially excludes the possibility that infection occurred within
the previous 4 months. Avidity index values should be considered within the context of other laboratory
findings and clinical signs.
Interpretation: < or = 0.50 Low Avidity Index 0.51 0.59 Intermediate Avidity Index > or = 0.60
High Avidity Index
Reference Values:
> or = 0.60
Reference Values:
Negative
Clinical References: 1. Espy M, Binnicker MJ: Comparison of six real-time PCR assays for the
qualitative detection of cytomegalovirus in clinical specimens. J Clin Microbiol 2013:51(11):3749-3752
2. Petito CK, Cho ES, Lemann W, et al: Neuropathy of acquired immunodeficiency syndrome (AIDS): an
autopsy review. J Neuropathol Exp Neurol 1986 November;45(6):635-646 3. Cinque P, Vago L, Dahl H,
et al: Polymerase chain reaction on cerebrospinal fluid for diagnosis of virus-associated opportunistic
diseases of the central nervous system in HIV-infected patients. AIDS 1996 August;10(9):951-958 4.
Broccolo F, Iulioano R, Careddu AM, et al: Detection of lymphotropic herpesvirus DNA by polymerase
chain reaction in cerebrospinal fluid of AIDS patients with neurological disease. Acta Virol 2000
June-August;44(3):137-143 5. Prosch S, Schielke E, Reip A, et al: Human cytomegalovirus (HCMV)
encephalitis in an immunocompetent young person and diagnostic reliability of HCMV DNA PCR using
cerebrospinal fluid of nonimmunosuppressed patients. J Clin Microbiol 1998
December;36(12):3636-3640 6. Sia IG, Patel R: New strategies for prevention and therapy of
cytomegalovirus infection and disease in solid-organ transplant recipients. Clin Microbiol Rev
2000;13:83-121
Useful For: Detection and quantification of cytomegalovirus (CMV) viremia Monitoring CMV
disease progression and response to antiviral therapy
Interpretation: The quantification range of this assay is 137 to 9,100,000 IU/mL (2.14 log to 6.96
log IU/mL), with a > or =95% limit of detection at 91 IU/mL (1.96 log IU/mL). A result of
"Undetected" indicates the absence of cytomegalovirus (CMV) DNA in the plasma (see Cautions
below). A result of "Detected, but <137 IU/mL (<2.14 log IU/mL)" indicates that CMV DNA is
detected in the plasma, but the assay cannot accurately quantify the CMV DNA present below this level.
A quantitative value (reported in IU/mL and log IU/mL) indicates the level of CMV DNA (ie, viral
load) present in the plasma. A result of "Detected, but >9,100,000 IU/mL (>6.96 log IU/mL)" indicates
that CMV DNA level present in plasma is above 9,100,000 IU/mL (6.96 log IU/mL), and the assay
cannot accurately quantify CMV DNA present above this level
Reference Values:
Undetected
Useful For: Antineutrophil cytoplasmic antibodies (cANCA and pANCA): -Evaluating patients
suspected of having autoimmune vasculitis (both Wegener granulomatosis [WG] and microscopic
polyangiitis) cANCA titer: -May be useful for monitoring treatment response in patients with WG
(systemic or organ-limited disease); increasing titer suggests relapse of disease, while a decreasing titer
suggests successful treatment When used for diagnosis it is recommended that specific tests for proteinase
3 (PR3) ANCA and myeloperoxidase (MPO) ANCA be performed in addition to testing for cANCA and
pANCA.(2) This panel of tests is available by ordering the VASC / Antineutrophil Cytoplasmic
Antibodies Vasculitis Panel, Serum.
Interpretation: Positive results for antineutrophil cytoplasmic antibodies (cANCA or pANCA) are
consistent with the diagnosis of Wegener granulomatosis (WG), either systemic WG with respiratory and
renal involvement or limited WG with more restricted end-organ involvement. Positive results for
pANCA are consistent with the diagnosis of autoimmune vasculitis including microscopic polyangiitis
(MPA) or pauci-immune necrotizing glomerulonephritis. Sequential measurements of titers of cANCA
may be useful to indicate the clinical course of patients with WG. Changes in titer of > or =2 serial
dilutions are considered significant.(3) In patients with very low levels of cANCA, the immunofluorescent
staining pattern may mimic the pANCA pattern. In patients with MPA, monitoring of disease activity may
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 672
be performed by measuring MPO ANCA (MPO / Myeloperoxidase Antibodies, IgG, Serum).
Reference Values:
Negative
If positive for cANCA, results are titered.
Clinical References: 1. Russell KA, Wiegert E, Schroeder DR, et al: Detection of anti-neutrophil
cytoplasmic antibodies under actual clinical testing conditions. Clin Immunol 2002:103;196-203 2.
Savige J, Gillis D, Benson E, et al: International consensus statement on testing and reporting of
antineutrophil cytoplasmic antibodies (ANCA). Am J Clin Pathol 1999:111;507-513 3. Specks U,
Homburger HA, DeRemee RA: Implications of cANCA testing for the classification of Wegeners
Granulomatosis: performance of different detection systems. Adv Exp Med Biol 1993:336;65-70
Useful For: Excluding the diagnosis of acute pulmonary embolism or deep vein thrombosis,
particularly when results of a sensitive D-dimer assay are combined with clinical information, including
pretest disease probability.(1-4) Diagnosis of intravascular coagulation and fibrinolysis, also known as
disseminated intravascular coagulation, especially when combined with clinical information and other
laboratory test data (eg, platelet count, assays of clottable fibrinogen and soluble fibrin monomer
complex, and clotting time assays-prothrombin time and activated partial thromboplastin time).(5)
Interpretation: A normal D-dimer result less than or equal to 500 ng/mL fibrinogen equivalent units
(FEU) on the IL D-Dimer HS500 kit has a negative predictive value of approximately 100% (range
97%-100%) and is FDA approved for the exclusion of acute pulmonary embolism (PE) and deep vein
thrombosis (DVT) when there is low or moderate pretest probability for PE or DVT. D-dimer
concentrations increase with age and, thus, the specificity for DVT and PE exclusion decreases with
age. For DVT or PE exclusion, in addition to clinical pretest probability, age-adjusted D-dimer cutoffs
are suggested for patients more than 50 years of age. Recent evidence suggests using clinical pretest
probability and age-adjusted cutoffs to improve the performance of D-dimer testing in patients greater
than 50 years of age. In recent studies, when compared to a fixed D-dimer cutoff, age adjusted D-dimer
cutoff values (calculated as follows: age [years] x 10 ng/mL) resulted in equivalent outcomes and no
additional false negative findings.(7-8) Increased D-dimer values are abnormal but do not indicate a
specific disease state. D-dimer values may be increased as a result of: -Clinical or subclinical
disseminated intravascular coagulation/intravascular coagulation and fibrinolysis -Other conditions
associated with increased activation of the procoagulant and fibrinolytic mechanisms such as recent
surgery, active or recent bleeding, hematomas, trauma, or thromboembolism -Association with
pregnancy, liver disease, inflammation, malignancy, or hypercoagulable (procoagulant) states The
degree of D-dimer increase does not definitely correlate with the clinical severity of associated disease
states.
Reference Values:
< or =500 ng/mL Fibrinogen Equivalent Units (FEU)
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D-dimer values < or =500 ng/mL FEU may be used in conjunction with clinical pretest probability to
exclude deep vein thrombosis (DVT) and pulmonary embolism (PE).
Clinical References: 1. Brill-Edward P, Lee A: D-dimer testing in the diagnosis of acute venous
thromboembolism. Thromb Haemost 1999 August;82(2):688-694 2. Heit JA, Minor TA, Andrews JC, et
al: Determinants of plasma fibrin D-dimer sensitivity for acute pulmonary embolism as defined by
pulmonary angiography. Arch Pathol Lab Med 1999 March;123(3):235-240 3. Heit JA, Meyers BJ,
Plumhoff EA, et al: Operating characteristics of automated latex immunoassay tests in the diagnosis of
angiographically-defined acute pulmonary embolism. Thromb Haemost 2000 June;83(6):970 4. Bates
SM, Grand'Maison A, Johnston M, et al: A latex D-dimer reliably excludes venous thromboembolism.
Arch Intern Med 2001 February;161(3):447-453 5. Levi M, ten Cate H: Disseminated intravascular
coagulation. N Engl J Med 1999 August;341(8):586-592 6. Feinstein DI, Marder VJ, Colman RW:
Consumptive thrombohemorrhagic disorders. In Hemostasis and Thrombosis: Basic Principles and
Clinical Practice. Third edition. Edited by RW Colman, J Hirsh, VJ Marder, et al. Philadelphia, PA, JB
Lippincott Co., 2001, pp 1197-1234 7. Righini M, Van Es J, Den Exter PL, et al: Age-Adjusted D-Dimer
Cutoff Levels to Rule Out Pulmonary Embolism: The ADJUST-PE Study. JAMA
2014;311(11):1117-1124. doi:10.1001/jama.2014.2135 8. Schouten HJ, Geersing GJ, Koek HL, et al:
Diagnostic accuracy of conventional or age adjusted D-dimer cut-off values in older patients with
suspected venous thromboembolism: systematic review and meta-analysis. BMJ 2013;346:f2492
Useful For: An adjunct to urine D-lactate (preferred), in the diagnosis of D-lactate acidosis
Interpretation: Increased levels are consistent with D-lactic acidosis. However, because D-lactate is
readily excreted, urine determinations are preferred.
Reference Values:
0.0-0.25 mmol/L
Clinical References: 1. Brandt RB, Siegel SA, Waters MG, Bloch MH: Spectrophotometric assay
for D-(-)-lactate in plasma. Anal Biochem1980;102(1):39-46 2. Petersen C: D-lactic acidosis. Nutr Clin
Pract 2005;20(6):634-645
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D-Lactate, Plasma). However, as D-lactate is readily excreted in urine, this is the preferred specimen for
D-lactate determinations.
Useful For: Preferred test for diagnosing D-lactate acidosis, especially in patients with jejunoileal
bypass and short-bowel syndrome
Clinical References: 1. Brandt RB, Siegel SA, Waters MG, Bloch MH: Spectrophotometric assay
for D-(-)-lactate in plasma. Anal Biochem 1980;102(1):39-46 2. Petersen C: D-lactic acidosis. Nutr Clin
Pract 2005 Dec;20(6):634-645
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens responsible for anaphylaxis, to confirm sensitization to particular allergens prior to
beginning immunotherapy, and to investigate the specificity of allergic reactions to insect venom
allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
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DAND Dandelion, IgE
82694 Clinical Information: Clinical manifestations of immediate hypersensitivity (allergic) diseases are
caused by the release of proinflammatory mediators (histamine, leukotrienes, and prostaglandins) from
immunoglobulin E (IgE)-sensitized effector cells (mast cells and basophils) when cell-bound IgE
antibodies interact with allergen. In vitro serum testing for IgE antibodies provides an indication of the
immune response to allergen(s) that may be associated with allergic disease. The allergens chosen for
testing often depend upon the age of the patient, history of allergen exposure, season of the year, and
clinical manifestations. In individuals predisposed to develop allergic disease(s), the sequence of
sensitization and clinical manifestations proceed as follows: eczema and respiratory disease (rhinitis and
bronchospasm) in infants and children less than 5 years due to food sensitivity (milk, egg, soy, and wheat
proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Synonym(s): Dantrium
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DATE Date, Fruit, IgE
82358 Clinical Information: Clinical manifestations of immediate hypersensitivity (allergic) diseases are
caused by the release of proinflammatory mediators (histamine, leukotrienes, and prostaglandins) from
immunoglobulin E (IgE)-sensitized effector cells (mast cells and basophils) when cell-bound IgE
antibodies interact with allergen. In vitro serum testing for IgE antibodies provides an indication of the
immune response to allergen(s) that may be associated with allergic disease. The allergens chosen for
testing often depend upon the age of the patient, history of allergen exposure, season of the year, and
clinical manifestations. In individuals predisposed to develop allergic disease(s), the sequence of
sensitization and clinical manifestations proceed as follows: eczema and respiratory disease (rhinitis and
bronchospasm) in infants and children less than 5 years due to food sensitivity (milk, egg, soy, and
wheat proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
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Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
4 17.5-49.9 Strongly positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
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0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: Diagnosing and differential diagnosis of hyperandrogenism (in conjunction with
measurements of other sex steroids) An initial screen in adults might include dehydroepiandrosterone
(DHEA)/dehydroepiandrosterone sulfate (DHEAS) and bioavailable testosterone measurement.
Depending on results, this may be supplemented with measurements of sex hormone-binding globulin
and occasionally other androgenic steroids (eg, 17-hydroxyprogesterone). An adjunct in the diagnosis of
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congenital adrenal hyperplasia (CAH); DHEA/DHEAS measurements play a secondary role to the
measurements of cortisol/cortisone, 17 alpha-hydroxyprogesterone, and androstenedione. Diagnosing
and differential diagnosis of premature adrenarche
Reference Values:
Premature: <40 ng/mL*
0-1 day: <11 ng/mL*
2-6 days: <8.7 ng/mL*
7 days-1 month: <5.8 ng/mL*
>1-23 months: <2.9 ng/mL*
2-5 years: <2.3 ng/mL
6-10 years: <3.4 ng/mL
11-14 years: <5.0 ng/mL
15-18 years: <6.6 ng/mL
19-30 years: <13 ng/mL
31-40 years: <10 ng/mL
41-50 years: <8.0 ng/mL
51-60 years: <6.0 ng/mL
> or =61 years: <5.0 ng/mL
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dominant pregnancy estrogen, estriol. Within weeks after birth, DHEA-S levels fall by 80% or more and
remain low until the onset of adrenarche. Adrenarche is a poorly understood phenomenon peculiar to
higher primates, which is characterized by a gradual rise in adrenal androgen production. It precedes
puberty but is not causally linked to it. Early adrenarche is not associated with early puberty or with any
reduction in final height or overt androgenization and is generally regarded as a benign condition, not
needing intervention. However, girls with early adrenarche may be at increased risk of polycystic ovarian
syndrome as adults, and some boys may develop early penile enlargement. Following adrenarche,
DHEA-S levels increase until the age of 20 to a maximum level roughly comparable to that observed at
birth. Levels then decline over the next 40 to 60 years to around 20% of peak levels. The clinical
significance of this age-related drop is unknown and trials of DHEA-S replacement in the elderly have not
produced convincing benefits. However, in young and old patients with primary adrenal failure, the
addition of DHEA-S to corticosteroid replacement has been shown in some studies to improve mood,
energy, and sex drive. Elevated DHEA-S levels can cause symptoms or signs of hyperandrogenism in
women. Men are usually asymptomatic, but through peripheral conversion of androgens to estrogens can
occasionally experience mild estrogen excess. Most mild to moderate elevations in DHEA-S levels are
idiopathic. However, pronounced elevations of DHEA-S may be indicative of androgen-producing
adrenal tumors. In small children, congenital adrenal hyperplasia (CAH) due to 3 beta-hydroxysteroid
deficiency is associated with excessive DHEA-S production. Lesser elevations may be observed in
21-hydroxylase deficiency (the most common form of CAH) and 11 beta-hydroxylase deficiency. By
contrast, steroidogenic acute regulatory protein or 17 alpha-hydroxylase deficiencies are characterized by
low DHEA-S levels. An initial workup in adults might also include total and bioavailable testosterone
(TTBS / Testosterone, Total and Bioavailable, Serum) measurements. Depending on results, this may be
supplemented with measurements of sex hormone-binding globulin (SHBG / Sex Hormone-Binding
Globulin [SHBG], Serum) and, occasionally other androgenic steroids (eg, 17-hydroxyprogesterone).
Useful For: Diagnosis and differential diagnosis of hyperandrogenism (in conjunction with
measurements of other sex steroids) An adjunct in the diagnosis of congenital adrenal hyperplasia
Diagnosis and differential diagnosis of premature adrenarche
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reference ranges is unknown. In most cases, the drug-induced changes are not large enough to cause
diagnostic confusion, but when interpreting mild abnormalities in DHEA-S levels, drug and hormone
interactions should be taken into account. Examples of drugs and hormones that can reduce DHEA-S
levels include: insulin, oral contraceptive drugs, corticosteroids, central nervous system agents that
induce hepatic enzymes (eg, carbamazepine, clomipramine, imipramine, phenytoin), many antilipemic
drugs (eg, statins, cholestyramine), domapinergic drugs (eg, levodopa/dopamine, bromocryptine), fish
oil, and vitamin E. Drugs that may increase DHEA-S levels include: metformin, troglitazone, prolactin,
(and by indirect implication many neuroleptic drugs), danazol, calcium channel blockers (eg, diltiazem,
amlodipine), and nicotine.
Reference Values:
Mean Age Reference Range (mcg/dL)
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DHEA treatment: myth or reality? Trends Endocrinol Metab 2002;13:288-294 6. Salek FS, Bigos KL,
Kroboth PD: The influence of hormones and pharmaceutical agents on DHEA and DHEA-S
concentrations: a review of clinical studies. J Clin Pharmacol 2002;42:247-266 7. Elmlinger MW, Kuhnel
W, Ranke MB: Reference ranges for serum concentrations of lutropin (LH), follitropin (FSH), estradiol
(E2), prolactin, progesterone, sex hormone binding globulin (SHBG), dehydroepiandrosterone sulfate
(DHEA-S), cortisol and ferritin in neonates, children, and young adults. Clin Chem Lab Med
2002;40(11):1151-1160
Useful For: Investigating new onset dementia and cognitive impairment plus 1 or more of the
following in serum specimens: -Rapid onset and progression -Fluctuating course -Psychiatric
accompaniments (psychosis, hallucinations) -Movement disorder (myoclonus, tremor, dyskinesias)
-Headache -Autoimmune stigmata (personal history or family history or signs of diabetes mellitus,
thyroid disorder, vitiligo, poliosis [premature graying], myasthenia gravis, rheumatoid arthritis,
systemic lupus erythematosus) -Smoking history (20+ pack years) or other cancer risk factors -History
of cancer -Inflammatory cerebral spinal fluid -Neuroimaging findings atypical for degenerative etiology
Interpretation: Antibodies specific for neuronal, glial, or muscle proteins are valuable serological
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markers of autoimmune dementia and of a patient's immune response to cancer. These autoantibodies
are not found in healthy subjects, and are usually accompanied by subacute neurological symptoms and
signs. It is not uncommon for more than 1 of the following autoantibodies to be detected in patients with
autoimmune dementia: -Plasma membrane antibodies (N-methyl-D-aspartate: NMDA receptor;
2-amino-3-[5-methyl-3-oxo-1,2- oxazol-4-yl] propanoic acid: AMPA receptor; gamma-amino butyric
acid: GABA-B receptor). These autoantibodies are all potential effectors of dysfunction. -Neuronal
nuclear autoantibody, type 1 (ANNA-1) or type 3 (ANNA-3). -Neuronal or muscle cytoplasmic
antibodies (amphiphysin, Purkinje cell antibody-type 2: PCA-2, collapsin response-mediator protein-5
neuronal: CRMP-5-IgG, or glutamic acid decarboxylase: GAD65 antibody).
Reference Values:
NEURONAL NUCLEAR ANTIBODIES
Antineuronal Nuclear Ab, Type 1 (ANNA-1)
<1:240
Antineuronal Nuclear Ab, Type 2 (ANNA-2)
<1:240
Antineuronal Nuclear Ab, Type 3 (ANNA-3)
<1:240
Anti-Glial/Neuronal Nuclear Ab, Type 1 (AGNA-1)
<1:240
WESTERN BLOT
Paraneoplastic Western Blot
Negative
CRMP-5-IgG Western Blot
Negative
Amphiphysin Western Blot
Negative
Useful For: Investigating new onset dementia and cognitive impairment plus 1 or more of the
following accompaniments in cerebrospinal specimens: -Rapid onset and progression -Fluctuating course
-Psychiatric accompaniments (psychosis, hallucinations) -Movement disorder (myoclonus, tremor,
dyskinesias) -Headache -Autoimmune stigmata (personal history or family history or signs of diabetes
mellitus, thyroid disorder, vitiligo, poliosis [premature graying], myasthenia gravis, rheumatoid arthritis,
systemic lupus erythematosus) -Smoking history (20+ pack years) or other cancer risk factors -History of
cancer -Inflammatory cerebral spinal fluid -Neuroimaging findings atypical for degenerative etiology
Interpretation: Antibodies specific for neuronal, glial, or muscle proteins are valuable serological
markers of autoimmune epilepsy and of a patient's immune response to cancer. These autoantibodies are
not found in healthy subjects, and are usually accompanied by subacute neurological symptoms and signs.
It is not uncommon for more than 1 of the following autoantibodies to be detected in patients with
autoimmune dementia. 1. Plasma membrane antibodies (N-methyl-D-aspartate (NMDA) receptor;
2-amino-3-(5-methyl-3-oxo-1,2- oxazol-4-yl) propanoic acid (AMPA) receptor; gamma-amino butyric
acid (GABA-B) receptor). These autoantibodies are all potential effectors of dysfunction. 2. Neuronal
nuclear autoantibody type 1 (ANNA-1) or type 3 (ANNA-3). 3. Neuronal or muscle cytoplasmic
antibodies (amphiphysin, Purkinje cell antibody-type 2 [PCA-2], collapsin response-mediator protein-5
neuronal [CRMP-5-IgG], or glutamic acid decarboxylase [GAD65] antibody).
Reference Values:
NEURONAL NUCLEAR ANTIBODIES
Antineuronal Nuclear Antibody-Type 1 (ANNA-1)
<1:2
Antineuronal Nuclear Antibody-Type 2 (ANNA-2)
<1:2
Antineuronal Nuclear Antibody-Type 3 (ANNA-3)
<1:2
Anti-Glial/Neuronal Nuclear Antibody-Type 1 (AGNA-1)
<1:2
WESTERN BLOT
Paraneoplastic Autoantibody, Western Blot Confirmation
Negative
Collapsin Response-Mediator Protein-5-IGG (CRMP-5-IGG) Western Blot
Negative
Amphiphysin Antibody Western Blot
Negative
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disease resolution. The absence of IgM-class antibodies to DV is consistent with lack of infection.
However, specimens drawn too soon following exposure may be negative for IgM antibodies to DV. If
DV remains suspected, a second specimen, drawn approximately 10 to 12 days following exposure
should be tested.
Reference Values:
IgG: Negative
IgM: Negative
Reference values apply to all ages.
Clinical References: 1. Bhatt S, Gething PW, Brady OJ, et al: The global distribution and burden of
dengue. Nature 2013;496:504-507 2. Dengue--an infectious disease of staggering proportions. Lancet
2013Jun 22;381(9884):2136 3. Rigau-Perez JG, Clark GG, Gubler DJ, et al: Dengue and dengue
haemorrhagic fever. Lancet 1998;352:971-977 4. Tang KF, Ooi EE: Diagnosis of dengue: an update.
Expert Rev Anti Infect Ther 2012;10:895-907 5. Guzman MG, Kouri G: Dengue diagnosis, advances and
challenges. Int J Infect Dis 2004;8:69-80
Reference Values:
IgG: Negative
IgM: Negative
NS1: Negative
Reference values apply to all ages.
Clinical References: 1. Bhatt S, Gething PW, Brady OJ, et al: The global distribution and burden
of dengue. Nature 2013;496:504-507 2. Dengue--an infectious disease of staggering proportions. Lancet
2013;381:2136 3. Rigau-Perez JG, Clark GG, Gubler DJ, et al: Dengue and dengue haemorrhagic fever.
Lancet 1998;352:971-977 4. Tang KF, Ooi EE: Diagnosis of dengue: an update. Expert Rev Anti Infect
Ther 2012;10:895-907 5. Guzman MG, Kouri G: Dengue diagnosis, advances and challenges. Int J
Infect Dis 2004;8:69-80
Reference Values:
Negative
Reference values apply to all ages.
Clinical References: 1. Bhatt S, Gething PW, Brady OJ, et al:The global distribution and burden
of dengue. Nature 2013;496:504-507 2. Dengue--an infectious disease of staggering proportions. Lancet
2013 Jun 22;381(9884):2136 3. Rigau-Perez JG, Clark GG, Gubler DJ, et al: Dengue and dengue
haemorrhagic fever. Lancet 1998;352:971-977 4. Tang KF, Ooi EE: Diagnosis of dengue: an update.
Expert Rev Anti Infect Ther 2012;10:895-907 5. Guzman MG, Kouri G: Dengue diagnosis, advances
and challenges. Int J Infect Dis 2004;8:69-80
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 689
DRPL Dentatorubral-Pallidoluysian Atrophy (DRPLA) Gene Analysis
35402 Clinical Information: Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal dominant
neurodegenerative disorder characterized by ataxia, choreoathetosis, dementia, and psychiatric
disturbance in adults and ataxia, myoclonus, seizures, and progressive intellectual deterioration in
children. Characteristic neuropathologic observations include degeneration of the dentatorubral and
pallidoluysian systems of the central nervous system. The prevalence of DRPLA depends on the
geographic and ethnic origin of the population being studied. DRPLA was first described in a European
individual without a family history; however, it is predominantly found as an inherited condition and is
most prevalent in Japan (0.2-0.7 per 100,000). Although rare, DRPLA has been identified in other
populations including Europe and North America. DRPLA is caused by an expansion of the CAG
trinucleotide repeat in the ATN1 (DRPLA) gene. This trinucleotide repeat is polymorphic in the general
population, with the number of repeats ranging from 7 to 35. In affected individuals the CAG expansion
ranges from 48 to 93 repeats. As with other trinucleotide repeat disorders, anticipation is frequently
observed, and larger CAG expansions are associated with earlier onset and a more severe and rapid
clinical course. In DRPLA, the observed anticipation appears to be significantly greater in paternal
transmissions.
The target value for treated post-menopausal adult females is the same as the Premenopausal reference
interval.
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infants and children 5 years due to food sensitivity (milk, egg, soy, and wheat proteins) followed by
respiratory disease (rhinitis and asthma) in older children and adults due to sensitivity to inhalant
allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Reference Values:
Diagnosis and description of microscopic findings
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acid residues in the N-terminal portion of the molecule. In normal liver, prothrombin undergoes
post-translational carboxylation before release into the peripheral blood. The carboxylation converts
specific amino-terminal glutamic acid residues to gamma-carboxyglutamic acid. The vitamin K
dependent carboxylase responsible for the carboxylation is absent in many hepatocellular carcinoma
(HCC) cells, and an abnormal prothrombin with all or some of unconverted glutamic acid is secreted.
Therefore, this noncarboxylated form (DCP) has been used as an HCC biomarker. DCP is considered a
complementary biomarker to alpha fetoprotein (AFP) and third electrophoretic form of lentil
lectin-reactive AFP% (AFP-L3%) for assessing the risk of developing HCC. The elevation of both
AFP-L3 and DCP indicate progression of HCC, albeit they reflect different features of the progression.
In a prospective study of patients in the United States with an established diagnosis of HCC, the
sensitivities for AFP, AFP-L3%, and DCP were 68%, 62%, and 73%, respectively. When the 3 markers
were combined, the sensitivity was 86%. In another study, DCP levels were shown to correlate with
tumor size and metastatic HCC. In this study, compared to AFP and AFP-L3%, DCP had the highest
sensitivity (87%) and the highest positive predictive value (87%) in patients with HCC due to chronic
hepatitis B and C infections. A number of studies have shown that elevated serum DCP is significantly
related to portal vein invasion and/or intrahepatic metastasis, which significantly affect prognosis for
patients with HCC. DCP can be elevated in other conditions besides HCC. Conditions such as
obstructive jaundice, intrahepatic cholestasis causing chronic decrease in vitamin K, and ingestion of
drugs such as warfarin or wide-spectrum antibiotics can result in high concentrations of DCP. In
addition, 25% to 50% of patients with HCC will have a DCP value within the reference range. Because
of this, a normal DCP value does not rule out HCC.
Useful For: Risk assessment of patients with chronic liver disease for development of hepatocellular
carcinoma (HCC) An aid in the monitoring of HCC patients post therapy if des-gamma-carboxy
prothrombin (DCP) level was elevated prior to therapy. An elevated DCP level is associated with
increased risk of recurring HCC.
Interpretation: In patients with an elevated des-gamma-carboxy prothrombin (DCP) result (> or =7.5
ng/mL), the risk of developing hepatocellular carcinoma (HCC) is 36.5% (95% CI 23.5%-49.6%). The
risk of developing HCC with a negative DCP result (<7.5 ng/mL) is 7.6% (95% CI 4.4%-10.8%).
Reference Values:
<7.5 ng/mL
Clinical References: 1. Carr B, Kanke F, Wise M, Satomura S: Clinical evaluation of Lens culinaris
agglutinin-reactive alpha-fetoprotein and des-gamma-carboxy prothrombin in histologically proven
hepatocellular carcinoma in the United States. Dig Dis Sci 2007;52:776-782 2. Durazo FA, Blatt LM,
Corey WG, et al: Des-gamma-carboxyprothrombin, alpha-fetoprotein and AFP-L3 in patients with
chronic hepatitis, cirrhosis and hepatocellular carcinoma. J Gastroenterol Hepatol 2008;23:1541-1548 3.
Marrero JA, Feng Z, Wang Y, et al: Alpha-fetoprotein, des-gamma carboxyprothrombin, and lectin-bound
alpha-fetoprotein in early hepatocellular carcinoma. Gastroenterology 2009;137:110-118 4. Bertino G,
Ardiri AM, Calvagno GS, et al: Prognostic and diagnostic value of des-gamma-carboxy prothrombin in
liver cancer. Drug News Perspect 2010 Oct;23(8):498-508
Useful For: Monitoring serum concentration during therapy Evaluating potential toxicity The test may
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also be useful to evaluate patient compliance
Interpretation: Most individuals display optimal response to desipramine with serum levels of 100
to 300 ng/mL. Some individuals may respond well outside of this range, or may display toxicity within
the therapeutic range; thus, interpretation should include clinical evaluation. Risk of toxicity is
increased with levels above 400 ng/mL.
Reference Values:
Therapeutic concentration: 100-300 ng/mL
Note: Therapeutic ranges are for specimens drawn at trough (ie, immediately before next scheduled
dose). Levels may be elevated in non-trough specimens.
Clinical References: 1. Wille SM, Cooreman SG, Neels HM, Lambert WE: Relevant issues in the
monitoring and toxicology of antidepressants. Crit Rev Clin Lab Sci 2008;45(1):25-89 2. Thanacoody
HK, Thomas SH: Antidepressant poisoning. Clin Med 2003;3(2):114-118 3. Hiemke C, Baumann P,
Bergemann N, et al: AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Psychiatry:
Update 2011. Pharmacopsychiatry 2011;44(6):195-235 4. Tietz Textbook of Clinical Chemistry and
Molecular Diagnostics. Edited by CA Burtis, ER Ashwood, DE Bruns. 2012 Fifth edition. Elsevier
Useful For: An aid in the identification of striated and smooth muscle cells and tumors derived from
this cell type
Interpretation: This test includes only technical performance of the stain (no pathologist
interpretation is performed). If diagnostic consultation by a pathologist is required order 70012 /
Pathology Consultation. The positive and negative controls are verified as showing appropriate
immunoreactivity. If a control tissue is not included on the slide, a scanned image of the relevant quality
control tissue is available upon request. Please contact 1-855-516-8404. Interpretation of this test should
be performed in the context of the patient's clinical history and other diagnostic tests by a qualified
pathologist.
Clinical References: 1. Attanoos RL, Griffin A, Gibbs AR: The use of immunohistochemistry in
distinguishing reactive from neoplastic mesothelium. A Novel use for Desmin and Comparative
Evaluation with Epithelial Membrane Antigen, p53, Platelet-Derived Growth Factor Receptor,
P-Glycoprotein and Bcl-2. Histopathology 2003;43(3):231-238 2. Pollock L. Rampling D, Greenwal
SE, Malone M: Desmin expression in rhabdomyosarcoma: Influence of the Desmin Clone and
Immunohistochemical Method. J Clin Pathol 1995;48(6):535-538 3. Rangdaeng S, Truong LD:
Comparative immunohistochemical staining for desmin and muscle-specific actin. A Study of 576
Cases. Am J Clin Pathol 1991;96(1):32-45
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notably desmoglein 1 (DSG1) in pemphigus foliaceus and desmoglein 3 (DSG3) and/or DSG1 in
pemphigus vulgaris. Desmogleins are protein substances located in and on the surface of keratinocytes.
These proteins have been shown to be a critical factor in cell-to-cell adhesion. Antibodies to
desmogleins can result in loss of cell adhesion, the primary cause of blister formation in pemphigus.
The diagnosis of pemphigus depends on biopsy and serum studies that characterize lesions and detect
the autoantibodies that cause them. Originally, the serum studies were performed by IIF using monkey
esophagus and other tissue substrates. The identification of the reactive antigens as DSG1 and DSG3
has made it possible to develop highly specific and sensitive enzyme-linked immunosorbent assay
methods.
Useful For: Preferred screening test for patients suspected to have an autoimmune blistering disorder
of the skin or mucous membranes (pemphigus) As an aid in the diagnosis of pemphigus Monitoring
treatment response in patients with a confirmed diagnosis of pemphigus
Interpretation: Antibodies to desmoglein 1 (DSG1) and desmoglein 3 (DSG3) have been shown to be
present in patients with pemphigus. Many patients with pemphigus foliaceus, a superficial form of
pemphigus have antibodies to DSG1. Patients with pemphigus vulgaris, a deeper form of pemphigus,
have antibodies to DSG3 and sometimes DSG1 as well. Antibody titer correlates in a semiquantitative
manner with disease activity in many patients. Patients with severe disease can usually be expected to
have high titers of antibodies to DSG. Titers are expected to decrease with clinical improvement. Our
experience demonstrates a very good correlation between DSG1 and DSG3 results and the presence of
pemphigus. Adequate sensitivities and specificity for disease are documented. However, in those patients
strongly suspected to have pemphigus either by clinical findings or by routine biopsy, and in whom the
DSG assay is negative, the IIF test (CIFS / Cutaneous Immunofluorescence Antibodies [IgG], Serum) is
recommended. For further information, see Cutaneous Immunofluorecence Testing in Special
Instructions.
Reference Values:
DESMOGLEIN 1
<14.0 U (negative)
14.0-20.0 U (indeterminate)
>20.0 U (positive)
DESMOGLEIN 3
<9.0 U (negative)
9.0-20.0 U (indeterminate)
>20.0 U (positive)
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Consultation. The positive and negative controls are verified as showing appropriate immunoreactivity. If
a control tissue is not included on the slide, a scanned image of the relevant quality control tissue is
available upon request. Please contact 1-855-516-8404. Interpretation of this test should be performed in
the context of the patient's clinical history and other diagnostic tests by a qualified pathologist.
Clinical References: Wahl JK 3rd: Generation of monoclonal antibodies specific for desmoglein
family members. Hybrid Hybridomics 2002;21:37-44
Reference Values:
An interpretative report will be provided.
Clinical References: 1. Barr FG, Chatten J, D'Cruz CM, et al: Molecular assays for chromosomal
translocations in the diagnosis of pediatric soft tissue sarcomas. JAMA 1995;273:553-557 2. Gerald
WL, Miller HK, Battifora H, et al: Intra-abdominal desmoplastic small round-cell tumor: Report of 19
cases of a distinctive type of high-grade polyphenotypic malignancy affecting young individuals. Am J
Surg Pathol 1991;15:499-513 3. Gerald WL, Rosai J, Ladanyi M: Characterization of the genomic
breakpoint and chimeric transcripts in the EWS-WT1 gene fusion of demoplastic, small round-cell
tumor. Proc Natl Acad Sci USA 1995;92:1028-1032 4. Jin L, Majerus J, Oliveira A, et al: Detection of
fusion gene transcripts in fresh-frozen and formalin-fixed paraffin-embedded tissue sections of soft
tissue sarcomas after laser capture microdissection and RT-PCR. Diagn Mol Pathol 2003;12:224-230
FDXM Dexamethasone
91956 Reference Values:
Units = ng/dL
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Adults baseline: <30
8:00 AM following 1 mg dexamethasone
previous evening: 140 - 295
8:00 AM following 8 mg dexamethasone
(4 x 2 mg doses) previous day: 1600 - 2850
Useful For: Distinguishing type 1 from type 2 diabetes mellitus Identifying individuals at risk of type 1
diabetes (including high-risk relatives of patients with diabetes) Predicting future insulin requirement
treatment in patients with adult-onset diabetes
Interpretation: Seropositivity for 1 or more islet cell autoantibodies is supportive of: -A diagnosis of
type 1 diabetes. Only 2% to 4% of patients with type 1 diabetes are antibody negative; 90% have more
than 1 antibody marker, and 70% have 3 markers.(1) Patients with gestational diabetes who are antibody
seropositive are at high risk for diabetes postpartum. Rarely, diabetic children test seronegative, which
may indicate a diagnosis of maturity-onset diabetes of the young in clinically suspicious cases. -A high
risk for future development of diabetes. Among 44 first-degree relatives of patients with type 1 diabetes,
those with 3 antibodies had a 70% risk of developing type 1 diabetes within 5 years.(3) -A current or
future need for insulin therapy in patients with diabetes. In the UK Prospective Diabetes Study, 84% of
those classified clinically as having type 2 diabetes and seropositive for glutamic acid decarboxylase 65
required insulin within 6 years, compared to 14% that were antibody negative.(4)
Reference Values:
GLUTAMIC ACID DECARBOXYLASE (GAD65) ANTIBODY
< or =0.02 nmol/L
Reference values apply to all ages.
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INSULIN ANTIBODIES
< or =0.02 nmol/L
Reference values apply to all ages.
Clinical References: 1. Bingley PJ: Clinical applications of diabetes antibody testing. J Clin
Endocrinol Metab 2010;95:25-33 2. Verge CF, Stenger D, Bonifacio E, et al: Combined use of
autoantibodies (IA-2 autoantibody, GAD autoantibody, insulin autoantibody, cytoplasmic islet cell
antibodies) in type 1 diabetes: Combinatorial Islet Autoantibody Workshop. Diabetes
1998;47:1857-1866 3. Bingley PJ, Gale EA: Progression to type 1 diabetes in islet cell
antibody-positive relatives in the European Nicotinamide Diabetes Intervention Trial: the role of
additional immune, genetic and metabolic markers of risk. Diabetologia 2006;49:881-890 4. Turner R,
Stratton I, Horton V, et al: UKPDS 25: autoantibodies to islet-cell cytoplasm and glutamic acid
decarboxylase for prediction of insulin requirement in type 2 diabetes. UK Prospective Diabetes Study
Group. Lancet 1997;350:1288-1293
Useful For: Assessing compliance Monitoring for appropriate therapeutic level Assessing toxicity
Interpretation: For seizures: Serum concentrations are not usually monitored during early therapy
because response to the drug can be monitored clinically as seizure control. If seizures resume despite
adequate therapy, another anticonvulsant must be considered. Toxicity is commonly seen when
diazepam plus nordiazepam concentrations exceed 3,000 ng/mL. Adverse effects of benzodiazepines in
therapeutic doses usually reflect the drug's pharmacology and include sedation, slurred speech, and
ataxia. Respiratory depression/arrest may occur with large overdoses or following rapid IV injection
with short-acting benzodiazepines.
Reference Values:
Therapeutic concentrations
Diazepam and Nordiazepam: 200-2,500 ng/mL
Clinical References: 1. Langman LJ, Bechtel L, Holstege CP: Chapter 35: Clinical Toxicology, In
Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Edited by CA Burtis, ER Ashwood,
DE Bruns. WB Saunders Company, Philadelphia, PA, 2011, pp 1109-1188 2. Tietz Textbook of
Clinical Chemistry and Molecular Diagnostics, Edited by CA Burtis, ER Ashwood, DE Bruns, WB
Saunders Company, Philadelphia, PA, 2011, Table 60.2, pp 1109-1188
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Digitoxin
Therapeutic Range: 10 - 30 ng/mL
Useful For: Evaluating recrudescent (breakthrough) digoxin toxicity in renal-failure patients Assessing
the need for more antidigoxin Fab to be administered Deciding when to reintroduce digoxin therapy
Monitoring patients with possible digoxin-like immunoreactive factors (DLIFs)
Interpretation: The target therapeutic is 0.4 to 1.5 ng/mL. Toxicity may be seen when free digoxin
concentrations are > or =3.0 ng/mL. Pediatric patients may tolerate higher concentrations. Therapeutic
concentrations for free digoxin are 25% lower than therapeutic values for total digoxin due to the
separation of protein-bound digoxin in the assay.
Reference Values:
Therapeutic concentration: 0.4-1.5 ng/mL
Toxic concentration: > or =3.0 ng/mL
Pediatric toxic concentrations may be higher.
Clinical References: 1. Jortani SA, Pinar A, Johnson NA, Valdes R Jr: Validity of unbound digoxin
measurements by immunoassays in presence of antidote (Digibind). Clin Chim Acta 1999;283:159-169 2.
Package insert: DIGIBIND Digoxin Immune FAB (Ovine). GlaxoSmithKline, Research Triangle Park
NC, 2003 3. Applied Therapeutic Drug Monitoring. Vol 2. Edited by TP Moyer, RL Boeckx. Washington
DC, American Association for Clinical Chemistry, 1984 4. Jortani SA, Voldes R Jr: Digoxin and its
related endogenous factors. Crit Rev Clin Lab Sci 1997;34:225-274 5. Datta P, Hinz V, Klee G:
Comparison four digoxin immunoassays with respect to interference from digoxin-like immunoreactive
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factors. Clin Biochem 1996;29(6):541-547 6. Soldin SJ: Free drug measurements. When and why? An
overview. Arch Pathol Lab Med 1999;123:822-823
Reference Values:
Therapeutic concentration: 0.5-2.0 ng/mL
Toxic concentration: > or =4.0 ng/mL
Pediatric toxic concentrations may be higher.
Reference values have not been established for patients that are <16 years of age.
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with Rac2 deficiency have been shown to have normal neutrophil oxidative burst when stimulated with
phorbol myristate acetate (PMA), indicating normal NADPH oxidase activity, but abnormal neutrophil
responses to N-formyl-methionyl-leucyl-phenylalanine (fMLP), which is a physiological activator of
neutrophils. The defective oxidative burst to fMLP, but not to PMA, indicates a signaling defect in Rac2
deficiency.(2)
Reference Values:
Result Name Unit Cutoff for defining normal
Clinical References: 1. Ambruso DR, Knall C, Abell AN, et al: Human neutrophil
immunodeficiency syndrome is associated with an inhibitory Rac2 mutation. Proc Natl Acad Sci U S A
2000;97:4654-4659 2. Accetta D, Syverson G, Bonacci B, et al: Human phagocyte defect caused by a
RAC2 mutation detected by means of neonatal screening for T cell lymphopenia. J Allergy Clin Immunol
2011;127:535-538
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measured by flow cytometry. Flow cytometry can distinguish between the different genetic forms of
CGD.(5, 6) Complete myeloperoxidase (MPO) deficiency can cause a false-positive result for CGD in the
DHR flow cytometric assay (7); however, there is a difference between the percent DHR+ neutrophils and
the mean fluorescence intensity (MFI) after PMA stimulation that allows discrimination between true
X-linked CGD and complete MPO deficiency. Further, the addition of recombinant human MPO
enhances the DHR signal in MPO-deficient neutrophils but not in CGD neutrophils.(7) It is important to
have quantitative measures in the DHR flow cytometry assay to effectively use the test for diagnosis of
the different forms of CGD as well as for monitoring chimerism and NADPH oxidase activity post-HCT.
These quantitative measures include assessment of the relative proportion (%) of neutrophils that are
positive for DHR fluorescence after PMA stimulation and the relative fluorescence intensity of DHR
(MFI) on neutrophils after activation. Female carriers of X-linked CGD can become symptomatic for
CGD due to skewed lyonization (X chromosome inactivation).(8) Age-related acquired skewing of
lyonization can also cause increased susceptibility to infections in carriers of X-linked CGD.(9) While
germline mutations are more common in CGD, there have been reports of de novo, sporadic mutations in
the CYBB gene, causing X-linked CGD in male patients whose mothers are not carriers for the affected
allele. Additionally, somatic mosaicism has been reported in patients with X-linked CGD who have small
populations of normal cells.(10) There are also reports of triple somatic mosaicism in female carriers
(11,12) as well as late-onset disease in an adult female who was a somatic mosaic for a novel mutation in
the CYBB gene.(13) Therefore, the clinical, genetic, and age spectrum of CGD is varied and laboratory
assessment of NADPH oxidase activity after neutrophil stimulation, coupled with appropriate
interpretation, is critical to achieving an accurate diagnosis or for monitoring patients posttransplant.
Useful For: Diagnosis of chronic granulomatous disease (CGD), X-linked and autosomal recessive
forms, complete myeloperoxidase (MPO) deficiency; monitoring chimerism and nicotinamide adenine
dinucleotide phosphate (NADPH) oxidase function posthematopoietic cell transplantation Assessing
residual NADPH oxidase activity pretransplant Identification of carrier females for X-linked CGD;
assessment of changes in lyonization with age in carrier females
Reference Values:
Result Name Unit Cutoff for defining normal
Control MFI PMA ox-DHR+ MFI > or =60 The appropriate age-related
reference values for Absolute Neutrophil
Count will be provided on the report.
Clinical References: 1. Kang EM, Marciano BE, DeRavin SS, et al: Chronic granulomatous
disease: overview and hematopoietic stem cell transplantation. J Allergy Clin Immunol
2011;127:1319-1326 2. Segal BH, DeCarlo ES, Kwon-Chung KJ, et al: Aspergillus nidulans infection
in chronic granulomatous disease. Medicine 1998;77:345-354 3. Matute JD, Arias AA, Wright NA, et
al: A new genetic subgroup of CGD with autosomal recessive mutations in p40phox and selective
defects in neutrophil NADPH oxidase activity. Blood 2009;114:3309-3315 4. Kuhns DB, Alvord WG,
Heller T, et al: Residual NADPH oxidase and survival in chronic granulomatous disease. N Engl J Med
2010;363:2600-2610 5. Vowells SJ, Fleisher TA, Sekhsaria S, et al: Genotype-dependent variability in
flow cytometric evaluation of reduced NADPH oxidase function in patients with CGD. J Pediatr
1996;128:104-107 6. Vowells SJ, Sekhsaria S, Malech H, et al: Flow cytometric analysis of the
granulocyte respiratory burst: a comparison study of fluorescent probes. J Immunol Methods
1995;178:89-97 7. Mauch L, Lun A, OGorman MRG, et al: CGD and complete MPO deficiency
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 701
both yield strongly reduced DHR 123 test signals but can be easily discerned in routine testing for CGD.
Clin Chem 2007;53:890-896 8. Roesler J: Carriers of X-linked CGD at risk. Clin Immunol
2009;130:233 9. Rosen-Wolff A, Soldan W, Heyne K, et al: Increased susceptibility of a carrier of
X-linked CGD to Aspergillus fumigatus infection associated with age-related skewing of lyonization.
Ann Hematol 2001;80:113-115 10. Yamada M, Okura Y, Suzuki Y, et al: Somatic mosaicism in two
unrelated patients with X-linked CGD characterized by the presence of a small population of normal
cells. Gene 2012;497:110-115 11. de Boer M, Bakker E, Van Lierde S, et al: Somatic triple mosaicism
in a carrier of X-linked CGD. Blood 1998;91:252-257 12. Noack D, Heyworth PG, Kyono W, et al: A
second case of somatic triple mosaicism in the CYBB gene causing CGD. Hum Genet
2001;109:234-238 13. Wolach B, Scharf Y, Gavrieli R, et al: Unusual late presentation of X-linked
CGD in an adult female with a somatic mosaic for a novel mutation in CYBB. Blood 2005;105:61-66
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 702
symptomatic for CGD due to skewed lyonization (X chromosome inactivation).(10) Age-related acquired
skewing of lyonization can also cause increased susceptibility to infections in carriers of X-linked
CGD.(11) While germline mutations are more common in CGD, there have been reports of de novo,
sporadic mutations in the CYBB gene, causing X-linked CGD in male patients whose mothers are not
carriers for the affected allele. Additionally, somatic mosaicism has been reported in patients with
X-linked CGD who have small populations of normal cells.(12) There are also reports of triple somatic
mosaicism in female carriers (13,14) as well as late-onset disease in an adult female who was a somatic
mosaic for a novel mutation in the CYBB gene.(15) Therefore, the clinical, genetic, and age spectrum of
CGD is varied and laboratory assessment of NADPH oxidase activity after neutrophil stimulation,
coupled with appropriate interpretation, is critical to achieving an accurate diagnosis or for monitoring
patients posttransplant.
Useful For: Diagnosis of chronic granulomatous disease (CGD), X-linked and autosomal recessive
forms, Rac2 deficiency, complete myeloperoxidase (MPO) deficiency; monitoring chimerism and
nicotinamide adenine dinucleotide phosphate (NADPH) oxidase function posthematopoietic cell
transplantation Assessing residual NADPH oxidase activity pretransplant Identification of carrier
females for X-linked CGD; assessment of changes in lyonization with age in carrier females
Reference Values:
Result Name Unit Cutoff for Defining Normal
Clinical References: 1. Kang EM, Marciano BE, DeRavin SS, et al: Chronic Granulomatous
Disease: Overview and hematopoietic stem cell transplantation. J Allergy Clin Immunol
2011;127:1319-1326 2. Segal BH, DeCarlo ES, Kwon-Chung KJ, et al: Aspergillus nidulans infection
in chronic granulomatous disease. Medicine 1998;77:345-354 3. Matute JD, Arias AA, Wright NA, et
al: A new genetic subgroup of CGD with autosomal recessive mutations in p40phox and selective
defects in neutrophil NADPH oxidase activity. Blood 2009;114:3309-3315 4. Kuhns DB, Alvord WG,
Heller T, et al: Residual NADPH oxidase and survival in Chronic Granulomatous Disease. N Engl J
Med 2010;363:2600-2610 5. Vowells SJ, Fleisher TA, Sekhsaria S, et al: Genotype-dependent
variability in flow cytometric evaluation of reduced NADPH oxidase function in patients with CGD. J
Pediatr 1996;128:104-107 6. Vowells SJ, Sekhsaria S, Malech H, et al: Flow cytometric analysis of the
granulocyte respiratory burst: a comparison study of fluorescent probes. J Immunol Methods
1995;178:89-97 7. Mauch L, Lun A, OGorman MRG, et al: CGD and complete MPO deficiency
both yield strongly reduced DHR 123 test signals but can be easily discerned in routine testing for CGD.
Clin Chem 2007;53:890-896 8. Ambruso DR, Knall C, Abell AN, et al: Human neutrophil
immunodeficiency syndrome is associated with an inhibitory Rac2 mutation. Proc Natl Acad Sci U S A
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 703
2000;97:4654-4659 9. Accetta D, Syverson G, Bonacci B, et al: Human phagocyte defect caused by a
RAC2 mutation detected by means of neonatal screening for T cell lymphopenia. J Allergy Clin
Immunol 2011;127:535-538 10. Roesler J: Carriers of X-linked CGD at risk. Clin Immunol
2009;130:233 11. Rosen-Wolff A, Soldan W, Heyne K, et al: Increased susceptibility of a carrier of
X-linked CGD to Aspergillus fumigatus infection associated with age-related skewing of lyonization.
Ann Hematol 2001:80:113-115 12. Yamada M, Okura Y, Suzuki Y, et al: Somatic mosaicism in two
unrelated patients with X-linked CGD characterized by the presence of a small population of normal
cells. Gene 2012:497:110-115 13. de Boer M, Bakker E, Van Lierde S, et al: Somatic triple mosaicism
in a carrier of X-linked CGD. Blood 1998;91:252-257 14. Noack D, Heyworth PG, Kyono W, et al: A
second case of somatic triple mosaicism in the CYBB gene causing CGD. Hum Genet
2001;109:234-238 15. Wolach B, Scharf Y, Gavrieli R, et al: Unusual late presentation of X-linked
CGD in an adult female with a somatic mosaic for a novel mutation in CYBB. Blood 2005;105:61-66
Reference Values:
Mean Age Reference Range (pg/mL)
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Stage V 18 years 240-650 >19 years: 112-955 pg/mL Females
Cord blood: < or =50 pg/mL < or =6 months:
< or =1,200 pg/mL Tanner Stages
Stage V 14.5 years < or =300 20-55 years: < or =300 pg/mL >55
years: < or =128 pg/mL 1. Pang S, Levine
LS, Chow D, et al: Dihydrotestosterone and its
relationship to testosterone in infancy and
childhood. J Clin Endocrinol Metab
1979;48:821-826 2. Stanczyk FZ: Diagnosis of
hyperandrogenism: biochemical criteria. Best
Pract Res Clin Endocrinol Metab
2006;20(2):177-191
Clinical References: 1. Bartsch G, Rittmaster RS, Klocker H: Dihydrotestosterone and the concept
of 5 alpha-reductase inhibition in human benign prostatic hyperplasia. World J Urol 2002;19(6):413-425
2. Trueb RM: Molecular mechanisms of androgenetic alopecia. Exp Gerontol 2002;37(8-9):981-990 3.
Singh SM, Gauthier S, Labrie F: Androgen receptor antagonists (antiandrogens): structure-activity
relationships. Curr Med Chem 2000;7(2):211-247 4. Rhodes L, Harper J, Uno H, et al: The effects of
finasteride (Proscar) on hair growth, hair cycle stage, and serum testosterone and dihydrotestosterone in
adult male and female stumptail macaques (Macaca arctoides). J Clin Endocrinol Metab 1994;79:991-996
5. Gustafsson O, Norming U, Gustafsson S, et al: Dihydrotestosterone and testosterone levels in men
screened for prostate cancer: a study of a randomized population. Br J Urol 1996;77:433-440
Useful For: Providing a comprehensive genetic evaluation for patients with a personal or family
history suggestive of hereditary dilated cardiomyopathy (DCM) Establishing a diagnosis of a hereditary
DCM, and in some cases, allowing for appropriate management and surveillance for disease features
based on the gene involved Identification of a pathogenic variant within a gene known to be associated
with disease features that allows for predictive testing of at-risk family members
Interpretation: Evaluation and categorization of variants is performed using the most recent published
American College of Medical Genetics and Genomics (ACMG) recommendations as a guideline. Variants
are classified based on known, predicted, or possible pathogenicity and reported with interpretive
comments detailing their potential or known significance. Multiple in silico evaluation tools may be used
to assist in the interpretation of these results. The accuracy of predictions made by in silico evaluation
tools is highly dependent upon the data available for a given gene, and predictions made by these tools
may change over time. Results from in silico evaluation tools should be interpreted with caution and
professional clinical judgment.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Hershberger RE, Kushner JD, Parks SB: Dilated Cardiomyopathy Overview.
In GeneReviews. 2007. Available at www.genetests.org 2. Hunt SA, Abraham WT, Chin MH, et al:
ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult.
Circulation 2005;112:e154-e235 3. Callis TE, Jensen BC, Weck KE, Willis MS: Evolving molecular
diagnostics for familial cardiomyopathies: at the heart of it all. Expert Rev Mol Diagn 2010
April;10:3:329-351 4. Herman DS, Lam L, Taylor MR, et al: Truncations of titin causing dilated
cardiomyopathy. N Engl J Med 2012;366(7):619-628 5. Dhandapany PS, Razzaque MA, Muthusami U, et
al: RAF1 mutations in childhood-onset dilated cardiomyopathy. Nat Genet 2014;46(6):635-639 6.
Hershberger RE, Morales A: Dilated Cardiomyopathy Overview. In GeneReviews. Edited by RA Pagon,
MP Adam, HH Ardinger, et al. University of Washington, Seattle. 1993-2014. Updated 2013 May 9.
Available at http://www.ncbi.nlm.nih.gov/books/NBK1309/ 7. Ackerman M, Priori SG, Willems S, et al:
HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and
cardiomyopathies. Heart Rhythm 2011;8:1308-1339
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DILL Dill, IgE
82602 Clinical Information: Clinical manifestations of immediate hypersensitivity (allergic) diseases are
caused by the release of proinflammatory mediators (histamine, leukotrienes, and prostaglandins) from
immunoglobulin E (IgE)-sensitized effector cells (mast cells and basophils) when cell-bound IgE
antibodies interact with allergen. In vitro serum testing for IgE antibodies provides an indication of the
immune response to allergen(s) that may be associated with allergic disease. The allergens chosen for
testing often depend upon the age of the patient, history of allergen exposure, season of the year, and
clinical manifestations. In individuals predisposed to develop allergic disease(s), the sequence of
sensitization and clinical manifestations proceed as follows: eczema and respiratory disease (rhinitis and
bronchospasm) in infants and children less than 5 years due to food sensitivity (milk, egg, soy, and
wheat proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
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<1.2
Normal ranges for children: Not clearly established, but similar to normal ranges for adults, except
for newborn infants whose results may not reach adult values until 3 to 6 months of age.
<1.2
Normal ranges for children: Not clearly established, but similar to normal ranges for adults, except for
newborn infants whose results may not reach adult values until 3 to 6 months of age.
DRVTI Dilute Russell Viper Venom Time (DRVVT), with Reflex, Plasma
63678 Clinical Information: Lupus anticoagulants (LA) are immunoglobulins (IgG, IgM, IgA, or a
combination of these) of autoimmune type that are specifically directed against antigenic complexes of
negatively charged phospholipids (such as phosphatidylserine or phosphatidylethanolamine) and
coagulation-related proteins such as beta-2-glycoprotein I (beta-2-GPI) or clotting factors including
prothrombin (factor II) or factor X, and cause prolongation of phospholipid-dependent clotting time tests
due to inhibition. LA are functionally and clinically distinct members of a broader group of
antiphospholipid autoantibodies (APA) that includes immunologically detectable anticardiolipin
antibodies or antibodies against other phospholipid-protein complexes. LA interfere with specific
coagulation factor-phospholipid interactions, typically causing prolongation of 1 or more
phospholipid-dependent clotting time tests (eg, activated partial thromboplastin time: APTT, dilute
Russell viper venom time: DRVVT) due to inhibition. This characteristic in vitro inhibition can be
overcome by addition of excess phospholipid. Because of the heterogeneous nature of LA antibodies, no
single coagulation test can identify or exclude all LA. Currently, the International Society on Thrombosis
and Haemostasis and the Clinical and Laboratory Standards Institute (CLSI) recommend testing for LA
with at least 2 phospholipid-dependent clotting time assays based on different coagulation pathways and
principles (eg, lupus sensitive APTT and DRVVT) In addition, given the potential for false-positive
results in patients on anticoagulants, a profile or panel of coagulation testing is recommended, including
the prothrombin time (PT), APTT, thrombin time (TT), and the DRVVT. If the PT, APTT, or DRVVT are
prolonged, additional testing may include mixing tests with normal plasma (to evaluate for inhibition) and
the use of excess phospholipid in appropriate assay systems to evaluate for phospholipid-dependent
inhibition. Additional reflexive testing helps determine the presence or absence of anticoagulants or
inhibitors to other factors. The diagnosis of LA requires performance and interpretation of complex
coagulation testing, as well as correlation with available clinical information, including evidence of
persistence of LA over time (> or =12 weeks). The venom obtained from the Russell viper (Vipera
russelli) contains enzymes that directly activate coagulation factors V and X, bypassing the activation of
factors VII, VIII, IX, XI, and XII, and, therefore, the effect of deficiencies or inhibitors of these factors.
Diluting the phospholipid necessary for the clotting factor interactions increases the sensitivity to LA and
the likelihood of identifying a phospholipid-dependent inhibitor that may not be detected by other
coagulation tests that have a higher phospholipid content (eg, LA-insensitive APTT reagents). The
DRVVT screen ratio test is one of several available in vitro tests that may be used to screen and confirm
the presence of LA or to help exclude LA. The DRVVT may be abnormally prolonged (DRVVT screen
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ratio > or =1.2) by LA as well as coagulation factor deficiencies, anticoagulant effects, or other types of
coagulation factor inhibitors. Specimens with abnormal results (DRVVT screen ratio > or =1.2) are
subjected to reflexive testing (DRVVT mix and confirmation ratios) as described in the Testing Algorithm
(also see Interpretation). It is advisable to use the DRVVT screen, mix and confirm ratio results in
conjunction with other appropriate coagulation tests (reflexive testing panels) to diagnose or exclude LA.
Although LA cause prolonged clotting times in vitro, there is a strong association with thrombosis risk.
However, not all patients with persisting LA develop thrombosis.
Useful For: Detecting and confirming or helping to exclude the presence of lupus anticoagulants
(LA) Identifying LA that do not prolong the activated partial thromboplastin time (APTT) Evaluating
unexplained prolongation of the APTT or prothrombin time clotting tests
Interpretation: Dilute Russell viper venom time (DRVVT) screen ratio (<1.2): A normal DRVVT
screen ratio (<1.2) indicates that lupus anticoagulants (LA) is not present, or not detectable, by this
method (but might be detected with other methods). Abnormal DRVVT screen ratio (DRVVT screen
ratio > or =1.2) may suggest the presence of LA; however, other possibilities include: -Deficiencies or
dysfunction of factors I (fibrinogen), II, V, or X, congenital or acquired. -Inhibitors of factor V, or
occasionally by inhibitors of factor VIII, or other specific or nonspecific inhibitors -Anticoagulation
therapy effects (see Cautions) Further evaluation consists of performing mixing studies with an equal
volume of normal pooled plasma (DRVVT 1:1 mix) to investigate the possibility of coagulation factor
deficiency (suggested by DRVVT mix ratio <1.2) and to evaluate inhibition (suggested by DRVVT mix
ratio > or =1.2) and mixing patient plasma with DRVVT reagent enriched in phospholipid (DRVVT
confirmatory reagent) (DRVVT mix and DRVVT confirm ratios). Possible combinations of results
include the following: -DRVVT screen ratio > or =1.2 and DRVVT mix ratio <1.2 DRVVT confirm
ratio <1.2: No evidence of LA. This data may reflect anticoagulation therapy effects or other (congenital
or acquired) coagulopathy. -DRVVT screen ratio > or =1.2 and DRVVT mix ratio > or =1.2 DRVVT
confirm ratio <1.2: The prolonged and inhibited DRVVT (DRVVT screen and mix ratios) may reflect
presence of a specific factor inhibitor (eg, factor V inhibitor), anticoagulation therapy effects, or other
nonspecific inhibitors as can be seen with monoclonal protein disorders, lymphoproliferative disease,
etc. Although LA cannot be conclusively excluded, the DRVVT confirm ratio of <1.2 makes this less
likely. -DRVVT screen ratio > or =1.2 and DRVVT mix ratio <1.2 DRVVT confirm ratio > or =1.2:
Although mixing study of the prolonged DRVVT (DRVVT screen and mix ratios) provides no evidence
of inhibition, additional phospholipid shortens the clotting time (DRVVT confirm ratio), suggesting
presence of LA. -DRVVT screen ratio > or =1.2 and DRVVT mix ratio > or =1.2 DRVVT confirm ratio
> or =1.2: The data are consistent with presence of LA, provided anticoagulant effect can be excluded
(see Cautions). Because no single coagulation test can identify or exclude all LAs, and because of the
complexity of testing LA, a combination or panel of coagulation tests is recommended: LUPPR / Lupus
Anticoagulant Profile THRMP / Thrombophilia Profile PROCT / Prolonged Clot Time Profile DRVVT
assays ordered as a single, stand-alone test should be interpreted within patient clinical context and
close attention to medication use by patient (see Cautions).
Reference Values:
Dilute Russell viper venom time screen ratio <1.2
Normal ranges for children: Not clearly established, but similar to normal ranges for adults, except for
newborn infants whose results may not reach adult values until 3 to 6 months of age.
Clinical References: 1. Proven A, Bartlett RP, Moder KG, et al: Clinical importance of positive
test results for lupus anticoagulant and anticardiolipin antibodies. Mayo Clin Proc 2004
April;79(4):467-475 2. Gastineau DA, Kazmier FJ, Nichols WL, Bowie EJ: Lupus anticoagulant: an
analysis of the clinical and laboratory features of 219 cases. Am J Hematol 1985 Jul;19(3):265-275 3.
Brandt JT, Triplett DA, Alving B, Sharrer I: Criteria for the diagnosis of lupus anticoagulants: an
update. On behalf of the Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the
Scientific and Standardisation Committee of the ISTH. Thromb Haemost 1995 Oct;74(4);1185-1190 4.
Arnout J, Vermylen J: Current status and implications of autoimmune antiphospholipid antibodies in
relation to thrombotic disease. J Thromb Haemost 2003 May;1(5):931-942 5. Pengo V, Tripodi A,
Reber G, et al: Update of the guidelines for lupus anticoagulant detection. Subcommittee on Lupus
Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the
International Society on Thrombosis and Haemostasis. J Thromb Haemost 2009;7:1737-1740 6. CLSI
Laboratory Testing for Lupus Anticoagulant; Approved Guideline. CLSI document H60-A. Wayne, PA:
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 709
Clinical and Laboratory Standards Institute; 2014
Interpretation: Results > or =0.01 IU/mL suggest a vaccine response. A diphtheria toxoid booster
should be considered for patients with anti-diphtheria toxoid IgG values between 0.01 and <0.1 IU/mL.
Reference Values:
Vaccinated: Positive (> or =0.01 IU/mL)
Unvaccinated: Negative (<0.01 IU/mL)
Clinical References: 1. Booy R, Aitken SJ, Taylor S, et al: Immunogenicity of combined diphtheria,
tetanus, and pertussis vaccine given at 2, 3, and 4 months versus 3, 5, and 9 months of age. Lancet
1992;339(8792):507-510 2. Maple PA, Efstratiou A, George RC, et al: Diphtheria immunity in UK blood
donors. Lancet 1995;345(8955):963-965 3. WHO meeting report: The Control of Diphtheria in Europe.
WHO ref:EUR/ICP/EPI/024 1990
Useful For: Assessment of an antibody response to tetanus and diphtheria toxoid vaccines An aid to
diagnose immunodeficiency
Interpretation: Diphtheria: Results > or =0.01 IU/mL suggest a vaccine response. A diphtheria
toxoid booster should be considered for patients with anti-diphtheria toxoid IgG values between 0.01
and <0.1 IU/mL Tetanus: Results > or =0.01 IU/mL suggest a vaccine response. A tetanus toxoid
booster should strongly be considered for patients with anti-tetanus toxoid IgG values between 0.01 and
0.5 IU/mL. Some cases of tetanus, usually mild, have occasionally been observed in patients who have a
measurable serum level of 0.01 to 1.0 IU/mL.
Reference Values:
DIPHTHERIA TOXOID IgG ANTIBODY
Vaccinated: Positive (> or =0.01 IU/mL)
Unvaccinated: Negative (<0.01 IU/mL)
Synonym(s): Persantine
Steady-state trough plasma concentrations following a three times daily regimen of:
50 mg: 0.1 - 1.5 mcg/mL
75 mg: 0.1 - 2.6 mcg/mL
Useful For: Demonstrating in vivo coating of RBCs with IgG or the complement component C3d in
the following settings: -Autoimmune hemolytic anemia -Hemolytic transfusion reactions -Drug-induced
hemolytic anemia
Interpretation: Negative: no IgG antibody or complement (C3d) detected on the surface of the red
cell. Positive: IgG or complement (C3d) is present on the surface of the red cell.
Reference Values:
Negative
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If positive, reaction is graded (micro positive to 4+).
Glucoamylase 24.6 27.4 48.7 18.2 66 * data from normal patients Units=uM/min/gram protein Interpretation
added.
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FDM1 DMPK DNA Test (DM1)
91592 Reference Values:
A final report will be attached in MayoAccess.
Useful For: Evaluating patients with signs and symptoms consistent with systemic lupus
erythematosus (SLE)
Interpretation: A positive test result for double-stranded DNA (dsDNA) antibodies is consistent
with the diagnosis of systemic lupus erythematosus. A reference range study conducted at the Mayo
Clinic demonstrated that, within a cohort of healthy adults (n=120), no individuals between the ages of
18 and 60 (n=78) had detectable anti-dsDNA antibodies. Above the age of 60 (n=42), 11.9% of
individuals (n=5) had a borderline result for dsDNA antibodies and 4.8% of individuals (n=2) had a
positive result.
Reference Values:
<30.0 IU/mL (negative)
30.0-75.0 IU/mL (borderline)
>75.0 IU/mL (positive)
Negative is considered normal.
Reference values apply to all ages.
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ADNA DNA Double-Stranded (dsDNA) Antibodies, IgG, Serum
8178 Clinical Information: Double-stranded (ds, native) DNA (dsDNA) antibodies of the IgG class are an
accepted criterion (American College of Rheumatology) for the diagnosis of systemic lupus
erythematosus (SLE).(1-3) dsDNA antibodies are detectable in approximately 85% of patients with
untreated SLE, and are rarely detectable in other connective tissue diseases. Weakly-positive results
caused by low-avidity antibodies to dsDNA are not specific for SLE and can occur in a variety of
diseases. Testing for IgG antibodies to dsDNA is indicated in patients who have a positive test for
antinuclear antibodies (ANA) along with signs and symptoms that are compatible with the diagnosis of
SLE. If the ANA test is negative, there is no reason to test for antibodies to dsDNA.(2) The levels of IgG
antibodies to dsDNA in serum are known to fluctuate with disease activity in lupus erythematosus, often
increasing prior to an increase in inflammation and decreasing in response to therapy.(1,2)
Useful For: Evaluating patients with signs and symptoms consistent with systemic lupus
erythematosus (SLE) Monitoring patients with documented SLE for flares in disease activity
Interpretation: A positive test result for double-stranded DNA (dsDNA) antibodies is consistent with
the diagnosis of systemic lupus erythematosus. A reference range study conducted at the Mayo Clinic
demonstrated that, within a cohort of healthy adults (n=120), no individuals between the ages of 18 and
60 (n=78) had detectable anti-dsDNA antibodies. Above the age of 60 (n=42), 11.9% of individuals (n=5)
had a borderline result for dsDNA antibodies and 4.8% of individuals (n=2) had a positive result.
Reference Values:
<30.0 IU/mL (negative)
30.0-75.0 IU/mL (borderline)
>75.0 IU/mL (positive)
Negative is considered normal.
Reference values apply to all ages.
Reference Values:
<0.35 kU/L
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proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Clinical References: 1. Lopes LF, West RB, Bacchi LM, et al: DOG1 for the diagnosis of
gastrointestinal stromal tumor (GIST): Comparison between 2 different antibodies. Appl
Immunohistochem Mol Morphol 2010 Jul;18(4):333-337 2. Miettinen M, Wang Z-F, Lasota J: DOG1
antibody in the differential diagnosis of gastrointestinal stromal tumors. Am J Surg Pathol 2009
Sep;33(9):1401-1408 3. Liegl B, Hornick JL, Corless CL, et al: Monoclonal antibody DOG1.1 shows
higher sensitivity than KIT in the diagnosis of gastrointestinal stromal tumors, including unusual
subtypes. Am J Surg Pathol 2009 Mar;33(3):437-446 4. Kitamura Y: Gastrointestinal stromal tumors:
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 715
past, present, and future. J Gastroenteral 2008;43:499-508 5. Espinosa I, Lee CH, Kim MK, et al: A
novel monoclonal antibody against DOG1 is a sensitive and specific marker for gastrointestinal stromal
tumors. Am J Surg Pathol 2008 Feb;32(2):210-218
Useful For: Influencing choice of antipsychotics prior to treatment, especially to ascertain if atypical
antipsychotics may be used with low risk of tardive dyskinesia Identifying those patients receiving
antipsychotics who are at increased risk of developing tardive dyskinesias. Individuals with the 25G allele
should be monitored closely for signs of tardive dyskinesia if a decision is made to treat with
antipsychotics. Testing may also be considered for individuals who will receive antipsychotic
medications, if they are first-degree relatives of patients who have developed tardive dyskinesia.
Assessing potential for effective treatment response with clozapine, olanzapine, and risperidone
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 716
Clinical References: 1. Lerer B, Segman RH, Fangerau H, et al: Pharmacogenetics of tardive
dyskinesia: combined analysis of 780 patients supports association with dopamine D3 receptor gene
Ser9Gly polymorphism. Neuropsychopharmacology 2002;27:105-119 2. de Leon J, Susce MT, Pan
RM, et al: Polymorphic variations in GSTM1, GSTT1, PgP, CYP2D6, CYP3A5, and dopamine D2 and
D3 receptors and their association with tardive dyskinesia in severe mental illness. J Clin
Psychopharmacol 2005;25:448-456 3. Scharfetter J, Chaudry HR, Hornik K, et al: Dopamine D3
receptor gene polymorphism and response to clozapine in schizophrenic Pakistani patients. Eur
Neuropsychopharmacol 1999;10(1):17-20 4. Lane HY, Hsu SK, Liu YC, et al: Dopamine D3 receptor
Ser9Gly polymorphism and risperidone response. J Clin Psychopharmacol 2005;25(1):6-11 5. Reynolds
GP, Yao Z, Zhang X, et al: Pharmacogenetics of treatment in first-episode schizophrenia: D3 and
5-HT2C receptor polymorphisms separately associate with positive and negative symptom response.
Eur Neuropsychopharmacol 2005;15:143-151
Useful For: Influencing choice of antipsychotics prior to treatment, especially to ascertain if atypical
antipsychotics may be used with low risk of tardive dyskinesia Identifying those patients receiving
antipsychotics who are at increased risk of developing tardive dyskinesias. Individuals with the 25G
allele should be monitored closely for signs of tardive dyskinesia if a decision is made to treat with
antipsychotics Testing may also be considered for individuals who will receive antipsychotic
medications, if they are first-degree relatives of patients who have developed tardive dyskinesia.
Assessing potential for effective treatment response with clozapine, olanzapine, and risperidone
Genotyping patients who prefer not to have venipuncture done
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Interpretation: An interpretive report will be provided.
Reference Values:
An interpretive report will be provided.
Useful For: Influencing the target dose of methylphenidate treatment for patients with attention
deficit/hyperactivity disorder Determining possible cause for poor response to methylphenidate in treated
patients with attention deficit/hyperactivity disorder
Clinical References: 1. Ding Y, Chi H-C, Grady D, et al: Evidence of positive selection acting at the
human dopamine receptor D4 gene locus. Proc Natl Acad Sci U S A 2002;99(1):309-314 2. Online
Inheritance in Man. Viewed on 4/01/2008 at URL:
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=126452 3. Kustanovich V, Ishii J, Crawford L, et
al: Transmission disequilibrium testing of dopamine-related candidate gene polymorphisms in ADHD:
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 718
confirmation of association of ADHD with DRD4 and DRD5. Mol Psychiatry 2004;9(7):711-717 4.
Hamarman S, Fossella J, Ulger C, et al: Dopamine receptor 4 (DRD4) 7-repeat allele predicts
methylphenidate dose response in children with attention deficit hyperactivity disorder: a
pharmacogenetic study. J Child Adolesc Psychopharmacol 2004;14(4):564-574
Useful For: Influencing the target dose of methylphenidate treatment for patients with attention
deficit/hyperactivity disorder Determining possible cause for poor response to methylphenidate in
treated patients with attention deficit/hyperactivity disorder Genotyping patients who prefer not to have
venipuncture done
Clinical References: 1. Ding Y, Chi HC, Grady D, et al: Evidence of positive selection acting at
the human dopamine receptor D4 gene locus. Proc Natl Acad Sci U S A 2002;99(1):309-314 2. Online
Inheritance in Man. National Center for Biotechnology Information, U.S. National Library of Medicine.
Viewed on 4/01/2008; no longer available on web site. 3. Kustanovich V, Ishii J, Crawford L, et al:
Transmission disequilibrium testing of dopamine-related candidate gene polymorphisms in ADHD:
confirmation of association of ADHD with DRD4 and DRD5. Mol Psychiatry 2004;9(7):711-717 4.
Hamarman S, Fossella J, Ulger C, et al: Dopamine receptor 4 (DRD4) 7-repeat allele predicts
methylphenidate dose response in children with attention deficit hyperactivity disorder: a
pharmacogenetic study. J Child Adolesc Psychopharmacol 2004;14(4):564-574
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: Monitoring therapy Evaluating potential toxicity Evaluating patient compliance
Interpretation: Most individuals display optimal response to doxepin when combined serum levels of
doxepin and nordoxepin are between 50 and 150 ng/mL. Some individuals may respond well outside of
this range, or may display toxicity within the therapeutic range; thus, interpretation should include clinical
evaluation. Risk of toxicity is increased with combined levels are above 500 ng/mL. Therapeutic ranges
are based on specimens drawn at trough (ie, immediately before the next dose).
Reference Values:
Therapeutic concentration (doxepin + nordoxepin): 50-150 ng/mL
Note: Therapeutic ranges are for specimens drawn at trough (ie, immediately before next scheduled
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 720
dose). Levels may be elevated in non-trough specimens.
Clinical References: 1. Wille SM, Cooreman SG, Neels HM, Lambert WE: Relevant issues in the
monitoring and the toxicology of antidepressants. Crit Rev Clin Lab Sci 2008;45(1):25-89 2.
Thanacoody HK, Thomas SH: Antidepressant poisoning. Clin Med 2003;3(2):114-118 3. Hiemke C,
Baumann P, Bergemann N, et al: AGNP Consensus Guidelines for Therapeutic Drug Monitoring in
Psychiatry: Update 2011. Pharmacopsychiatry 2011;44(6):195-235 4. Tietz Textbook of Clinical
Chemistry and Molecular Diagnostics. Edited by CA Burtis, ER Ashwood, DE Bruns. 2012. Fifth
edition. Elsevier
Useful For: Detecting drug abuse involving amphetamines, barbiturates, benzodiazepines, cocaine,
ethanol, marijuana, opiates, and phencyclidine This test is intended to be used in a setting where the test
results can be used definitively to make a diagnosis. Chain of custody is required whenever the results
of testing could be used in a court of law. Its purpose is to protect the rights of the individual
contributing the specimen by demonstrating that it was under the control of personnel involved with
testing the specimen at all times; this control implies that the opportunity for specimen tampering would
be limited.
Interpretation: A positive result indicates that the patient has used the drugs detected in the recent
past. See individual tests (eg, AMPHX / Amphetamines Confirmation, Chain of Custody, Urine) for
more information. For information about drug testing, including estimated detection times, see Drugs of
Abuse Testing at http://www.mayomedicallaboratories.com/test-info/drug-book/index.html
Reference Values:
Negative
Screening cutoff concentrations
Amphetamines: 500 ng/mL
Barbiturates: 200 ng/mL
Benzodiazepines: 100 ng/mL
Cocaine (benzoylecgonine-cocaine metabolite): 150 ng/mL
Ethanol: 10 mg/dL
Opiates: 300 ng/mL
Phencyclidine: 25 ng/mL
Tetrahydrocannabinol carboxylic acid: 50 ng/mL
This report is intended for use in clinical monitoring or management of patients. It is not intended for
use in employment-related testing.
Clinical References: 1. Physicians Desk Reference (PDR). 60th edition. Montvale, NJ, Medical
Economics Company, 2006 2. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 11th
edition. Edited by LL Bruntman. New York, McGraw-Hill Book Company, 2006 3. Langman LJ,
Bechtel L, Holstege CP: Chapter 35. In Tietz Textbook of Clinical Chemistry and Molecular
Diagnostics. Edited by CA Burtis, ER Ashwood, DE Bruns. WB Saunders Company, 2011, pp
1109-1188
Useful For: Detecting drug abuse involving amphetamines, cocaine, marijuana, opiates, and
phencyclidine This chain-of-custody test is intended to be used in a setting where the test results can be
used definitively to make a diagnosis.
Reference Values:
Negative
Screening cutoff concentrations
Amphetamines: 500 ng/mL
Cocaine (benzoylecgonine-cocaine metabolite): 150 ng/mL
Opiates: 300 ng/mL
Phencyclidine: 25 ng/mL
Tetrahydrocannabinol carboxylic acid: 50 ng/mL
This report is intended for use in clinical monitoring or management of patients. It is not intended for use
in employment-related testing.
Clinical References: 1. Physicians Desk Reference (PDR). 60th edition. Montvale, NJ, Medical
Economics Company, 2006 2. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 11th
edition. Edited by LL Bruntman. New York, McGraw-Hill Book Company, 2006 3. Langman LJ, Bechtel
L, Holstege CP: Chapter 35. In Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Edited
by CA Burtis, ER Ashwood, DE Bruns. WB Saunders Company, 2011, pp 1109-1188
Useful For: Detecting drug abuse involving amphetamines, cocaine, marijuana, opiates, and
phencyclidine This test is intended to be used in a setting where the test results can be used definitively to
make a diagnosis. Some drug treatment programs do not require confirmatory testing of screen-positive
specimens. In those settings, UDOA / Drug Abuse Survey, Urine is a less costly option.
Interpretation: A positive result indicates that the patient has used the drugs detected in the recent
past. See individual tests (eg, AMPHU / Amphetamines Confirmation, Urine) for more information. For
information about drug testing, including estimated detection times, see Drugs of Abuse Testing at
http://www.mayomedicallaboratories.com/test-info/drug-book/index.html
Reference Values:
Negative
Screening cutoff concentrations
Amphetamines: 500 ng/mL
Cocaine (benzoylecgonine-cocaine metabolite): 150 ng/mL
Opiates: 300 ng/mL
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 722
Phencyclidine: 25 ng/mL
Tetrahydrocannabinol carboxylic acid: 50 ng/mL
This report is intended for use in clinical monitoring or management of patients. It is not intended for use
in employment-related testing.
Clinical References: 1. Physician's Desk Reference (PDR). 60th edition. Montvale, NJ, Medical
Economics Company, 2006 2. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 11th
edition. Edited by LL Bruntman. New York, McGraw-Hill Book Company, 2006 3. Langman LJ,
Bechtel L, Holstege CP: Chapter 35: Tietz Textbook of Clinical Chemistry and Molecular Diagnostics.
Edited by CA Burtis, ER Ashwood, DE Bruns. WB Saunders Company, 2011, pp 1109-1188
Useful For: Detecting drug abuse involving alcohol, amphetamines, barbiturates, benzodiazepines,
cocaine, methadone, opiates, phencyclidine, and tetrahydrocannabinol This chain-of-custody test is
intended to be used in a setting where the test results can be used definitively to make a diagnosis.
Interpretation: A positive result indicates that the patient has used the drugs detected in the recent
past. See individual tests (eg, AMPHX / Amphetamines Confirmation, Chain of Custody, Urine) for
more information. For information about drug testing, including estimated detection times, see Drugs of
Abuse Testing at http://www.mayomedicallaboratories.com/test-info/drug-book/index.html
Reference Values:
Negative
Screening cutoff concentrations
Amphetamines: 500 ng/mL
Barbiturates: 200 ng/mL
Benzodiazepines: 100 ng/mL
Cocaine (benzoylecgonine-cocaine metabolite): 150 ng/mL
Ethanol: 10 mg/dL
Methadone metabolite: 300 ng/mL
Opiates: 300 ng/mL
Phencyclidine: 25 ng/mL
Tetrahydrocannabinol carboxylic acid: 50 ng/mL
This report is intended for use in clinical monitoring or management of patients. It is not intended for
use in employment-related testing.
Clinical References: 1. Physicians Desk Reference (PDR). 60th edition. Montvale, NJ, Medical
Economics Company, 2006 2. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 11th
edition. Edited by LL Bruntman. New York, McGraw-Hill Book Company, 2006 3. Langman LJ,
Bechtel L, Holstege CP: Chapter 35. In Tietz Textbook of Clinical Chemistry and Molecular
Diagnostics. Edited by CA Burtis, ER Ashwood, DE Bruns. WB Saunders Co, 2011, pp 1109-1188
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 723
CDAU7 Drug Abuse Survey with Confirmation, Panel 9, Urine
81410 Clinical Information: This assay was designed to test for and confirm by gas chromatography-mass
spectrometry (GC-MS) or liquid chromatography-tandem mass spectrometry (LC-MS/MS) the most
common classes of drugs of abuse. This test uses the simple screening technique which involves
immunologic testing for drugs by class. All positive screening results are confirmed by GC-MS (positive
alcohol by GC) or LC-MS/MS, and quantitated, before a positive result is reported. This test represents
the coupling of UDOA / Drug Abuse Survey, Urine with an automatic confirmation of all positive results
by the definitive assay available and described elsewhere (eg, AMPHU / Amphetamines Confirmation,
Urine).
Useful For: Detecting drug abuse involving alcohol, amphetamines, barbiturates, benzodiazepines,
cocaine, methadone, opiates, phencyclidine, and tetrahydrocannabinol This test is intended to be used in a
setting where the test results can be used definitively to make a diagnosis
Reference Values:
Negative
Screening cutoff concentrations
Amphetamines: 500 ng/mL
Barbiturates: 200 ng/mL
Benzodiazepines: 100 ng/mL
Cocaine (benzoylecgonine-cocaine metabolite): 150 ng/mL
Ethanol: 10 mg/dL
Methadone metabolite: 300 ng/mL
Opiates: 300 ng/mL
Phencyclidine: 25 ng/mL
Tetrahydrocannabinol carboxylic acid: 50 ng/mL
This report is intended for use in clinical monitoring or management of patients. It is not intended for use
in employment-related testing.
Clinical References: 1. Physician's Desk Reference (PDR). 60th edition. Montvale, NJ, Medical
Economics Company, 2006 2. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 11th
edition. Edited by LL Bruntman. New York, McGraw-Hill Book Company, 2006 3. Langman LJ, Bechtel
L, Holstege CP. In Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Edited by CA
Burtis, ER Ashwood, DE Bruns. Chapter 35. WB Saunders Co, 2011, pp 1109-1188
Useful For: Detecting drug abuse involving amphetamines, barbiturates, benzodiazepines, cocaine,
ethanol, marijuana, opiates, and phencyclidine This test is intended to be used in a setting where the test
results can be used definitively to make a diagnosis.
Interpretation: A positive result indicates that the patient has used the drugs detected in the recent
past. See individual tests (eg, AMPHU / Amphetamines, Urine) for more information. For information
about drug testing, including estimated detection times, see Drugs of Abuse Testing at
http://www.mayomedicallaboratories.com/test-info/drug-book/index.html
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 724
Reference Values:
Negative
Screening cutoff concentrations
Amphetamines: 500 ng/mL
Barbiturates: 200 ng/mL
Benzodiazepines: 100 ng/mL
Cocaine (benzoylecgonine-cocaine metabolite): 150 ng/mL
Ethanol: 10 mg/dL
Opiates: 300 ng/mL
Phencyclidine: 25 ng/mL
Tetrahydrocannabinol carboxylic acid: 50 ng/mL
This report is intended for use in clinical monitoring or management of patients. It is not intended for
use in employment-related testing.
Clinical References: 1. Physician's Desk Reference (PDR). 60th edition. Montvale, NJ, Medical
Economics Company, 2006 2. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 11th
edition. Edited by LL Bruntman. New York, McGraw-Hill Book Company, 2006 3. Langman LJ,
Bechtel L, Holstege CP: Chapter 35. In Tietz Textbook of Clinical Chemistry and Molecular
Diagnostics. Edited by CA Burtis, ER Ashwood, DE Bruns. WB Saunders Company, 2011, pp
1109-1188
Useful For: Detection and identification of prescription or over the counter drugs frequently found in
drug overdose or used with a suicidal intent This test is designed to qualitatively identify drugs present
in the specimen; quantification of identified drugs, when available, may be performed upon client
request. Chain of custody is required whenever the results of testing could be used in a court of law. Its
purpose is to protect the rights of the individual contributing the specimen by demonstrating that it was
under the control of personnel involved with testing the specimen at all times; this control implies that
the opportunity for specimen tampering would be limited.
Interpretation: The drugs that are detected by this test are listed in Prescription and
Over-the-Counter (OTC) Drug Screens Table 1 in Special Instructions. The pharmacology of each drug
determines how the test should be interpreted. A detailed discussion of each drug is beyond the scope of
this text. If you wish to have a report interpreted, call Mayo Medical Laboratories and ask for a
toxicology consultant. Each report will indicate the drugs detected.
Reference Values:
Drugs detected are presumptive. Additional testing may be required to confirm the presence of any
drugs detected.
Clinical References: 1. Langman LJ, Bechtel L, Holstege CP: Clinical toxicology. In Tietz
Textbook of Clinical Chemistry and Molecular Diagnostics. Edited by CA Burtis, ER Ashwood, DE
Bruns. Fifth edition. St. Louis, MO, Elsevier Saunders, 2012 pp 1109-1188 2. Disposition of Toxic
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 725
Drugs and Chemicals in Man. 10th edition. Edited by RC Baselty. South Beach CA, Biomedical
Publications, 2014
Useful For: The qualitative detection and identification of prescription or over-the-counter drugs
frequently found in drug overdose or used with a suicidal intent This test is designed to provide, when
possible, the identification of all drugs present. Chain of custody is required whenever the results of
testing could be used in a court of law. Its purpose is to protect the rights of the individual contributing the
specimen by demonstrating that it was under the control of personnel involved with testing the specimen
at all times; this control implies that the opportunity for specimen tampering would be limited.
Interpretation: The drugs that can be detected by this test are listed in Prescription and
Over-the-Counter (OTC) Drug Screens in Special Instructions. Drugs of toxic significance that are not
detected by this test include digoxin, lithium, many drugs of abuse or illicit drugs, some benzodiazepines,
and some opiates. For these drugs, see Mayo Medical Laboratories' drug abuse surveys or drug screens or
individual tests. A detailed discussion of each drug detected is beyond the scope of this text. Each report
will indicate the drugs identified. If a clinical interpretation is required, request a Drug/Toxicology Lab
consult (Mayo Clinic patients) or contact Mayo Laboratory Inquiry (Mayo Medical Laboratories clients).
Reference Values:
Drugs detected are presumptive. Additional testing may be required to confirm the presence of any drugs
detected.
Clinical References: 1. Langman LJ, Bechtel L, Holstege CP: Clinical toxicology. In Tietz
Textbook of Clinical Chemistry and Molecular Diagnostics. Fifth edition. Edited by CA Burtis, ER
Ashwood, DE Bruns. St. Louis, MO. Elsevier Saunders, 2012 pp 1109-1188 2. Disposition of Toxic
Drugs and Chemicals in Man. 10th edition. Edited by RC Baselty. South Beach, CA, Biomedical
Publications, 2014
Useful For: Detection and identification of prescription or over the counter drugs frequently found in
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 726
drug overdose or used with a suicidal intent This test is designed to qualitatively identify drugs present in
the specimen; quantification of identified drugs, when available, may be performed upon client request
Interpretation: The drugs that are detected by this test are listed in Prescription and
Over-the-Counter (OTC) Drug Screens in Special Instructions. The pharmacology of each drug
determines how the test should be interpreted. A detailed discussion of each drug is beyond the scope of
this text. If you wish to have a report interpreted, call Mayo Medical Laboratories and ask for a
toxicology consultant. Each report will indicate the drugs detected.
Reference Values:
Drugs detected are presumptive. Additional testing may be required to confirm the presence of any
drugs detected.
Clinical References: 1. Langman LJ, Bechtel L, Holstege CP: Clinical toxicology. In Tietz
Textbook of Clinical Chemistry and Molecular Diagnostics. Edited by CA Burtis, ER Ashwood, DE
Bruns. Fifth edition. St. Louis, MO, Elsevier Saunders, 2012 pp 1109-1188 2. Disposition of Toxic
Drugs and Chemicals in Man. 10th edition. Edited by RC Baselty. South Beach CA, Biomedical
Publications, 2014
Useful For: The qualitative detection and identification of prescription or over-the-counter drugs
frequently found in drug overdose or used with a suicidal intent This test is designed to provide, when
possible, the identification of all drugs present.
Interpretation: The drugs that can be detected by this test are listed in Prescription and
Over-the-Counter (OTC) Drug Screens in Special Instructions. Drugs of toxic significance that are not
detected by this test include digoxin, lithium, many drugs of abuse/illicit drugs, some benzodiazepines,
and some opiates. For these drugs, see Mayo Medical Laboratories' drug abuse surveys or drug screens
or individual tests. A detailed discussion of each drug detected is beyond the scope of this text. Each
report will indicate the drugs identified. If a clinical interpretation is required, request a
Drug/Toxicology Lab consult (Mayo Clinic patients) or contact Mayo Laboratory Inquiry (Mayo
Medical Laboratories clients).
Reference Values:
Drugs detected are presumptive. Additional testing may be required to confirm the presence of any
drugs detected.
Clinical References: 1. Langman LJ, Bechtel L, Holstege CP: Clinical toxicology. In Tietz
Textbook of Clinical Chemistry and Molecular Diagnostics. Fifth edition. Edited by CA Burtis, ER
Ashwood, DE Bruns. St. Louis, MO. Elsevier Saunders, 2012 pp 1109-1188 2. Disposition of Toxic
Drugs and Chemicals in Man. 10th edition. Edited by RC Baselty. South Beach CA, Biomedical
Publications, 2014
Interpretation: The limit of quantitation varies for each of these drug groups. -Amphetamines: >100
ng/g -Methamphetamines: >100 ng/g -Cocaine and metabolite: >100 ng/g -Opiates: >100 ng/g
-Tetrahydrocannabinol carboxylic acid: >20 ng/g
Reference Values:
Negative
Positives are reported with a quantitative LC-MS/MS result.
Cutoff concentrations
Amphetamines by ELISA: 100 ng/g
Methamphetamine by ELISA: 100 ng/g
Benzoylecgonine (cocaine metabolite) by ELISA: 100 ng/g
Opiates by ELISA: 100 ng/g
Tetrahydrocannabinol carboxylic acid (marijuana metabolite) by ELISA: 20 ng/g
Clinical References: 1. Ostrea EM Jr: Understanding drug testing in the neonate and the role of
meconium analysis. J Perinat Neonatal Nurs 2001 Mar;14(4):61-82; quiz 105-106 2. Ostrea EM Jr, Brady
MJ, Parks PM, et al: Drug screening of meconium in infants of drug-dependent mothers: an alternative to
urine testing. J Pediatr 1989 Sep;115(3):474-477 3. Ahanya SN, Lakshmanan J, Morgan BL, Ross MG:
Meconium passage in utero mechanisms, consequences, and management. Obstet Gynecol Surv 2005
Jan;60(1):45-56; quiz 73-74
Interpretation: The limit of quantitation varies for each of these drug groups. -Amphetamines: >100
ng/g -Methamphetamines: >100 ng/g -Cocaine and metabolite: >100 ng/g -Opiates: >100 ng/g
-Tetrahydrocannabinol carboxylic acid: >20 ng/g -Phencyclidine (PCP): >20 ng/g
Reference Values:
Negative
Positives are reported with a quantitative LC-MS/MS result.
Cutoff concentrations
Amphetamines by ELISA: 100 ng/g
Methamphetamine by ELISA: 100 ng/g
Benzoylecgonine (cocaine metabolite) by ELISA: 100 ng/g
Opiates by ELISA: 100 ng/g
Tetrahydrocannabinol carboxylic acid (marijuana metabolite) by ELISA: 20 ng/g
Phencyclidine by ELISA: 20 ng/g
Clinical References: 1. Ostrea EM Jr: Understanding drug testing in the neonate and the role of
meconium analysis. J Perinat Neonatal Nurs 2001 Mar;14(4):61-82; quiz 105-106 2. Ostrea EM Jr,
Brady MJ, Parks PM, et al: Drug screening of meconium in infants of drug-dependent mothers; an
alternative to urine testing. J Pediatr 1989 Sep;115(3):474-477 3. Ahanya SN, Lakshmanan J, Morgan
BL, Ross MG: Meconium passage in utero: mechanisms, consequences, and management. Obstet
Gynecol Surv 2005 Jan;60(1):45-56; quiz 73-74
Interpretation: The limit of quantitation varies for each of these drug groups. -Amphetamines: >100
ng/g -Methamphetamines: >100 ng/g -Cocaine and metabolite: >100 ng/g -Opiates: >100 ng/g
-Tetrahydrocannabinol carboxylic acid: >20 ng/g
Reference Values:
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 729
Negative
Positives are reported with a quantitative LC-MS/MS result.
Cutoff concentrations
Amphetamines by ELISA: 100 ng/g
Methamphetamine by ELISA: 100 ng/g
Benzoylecgonine (cocaine metabolite) by ELISA: 100 ng/g
Opiates by ELISA: 100 ng/g
Tetrahydrocannabinol carboxylic acid (marijuana metabolite) by ELISA: 20 ng/g
Clinical References: 1. Ostrea EM Jr: Understanding drug testing in the neonate and the role of
meconium analysis. J Perinat Neonatal Nurs 2001 Mar;14(4):61-82; quiz 105-106 2. Ostrea EM Jr, Brady
MJ, Parks PM, et al: Drug screening of meconium in infants of drug-dependent mothers: an alternative to
urine testing. J Pediatr 1989 Sep;115(3):474-477 3. Ahanya SN, Lakshmanan J, Morgan BL, Ross MG:
Meconium passage in utero mechanisms, consequences, and management. Obstet Gynecol Surv 2005
Jan;60(1):45-56; quiz 73-74
Interpretation: The limit of quantitation varies for each of these drug groups. -Amphetamines: >100
ng/g -Methamphetamines: >100 ng/g -Cocaine and metabolite: >100 ng/g -Opiates: >100 ng/g
-Tetrahydrocannabinol carboxylic acid: >20 ng/g -Phencyclidine (PCP): >20 ng/g
Reference Values:
Negative
Positives are reported with a quantitative LC-MS/MS result.
Cutoff concentrations
Amphetamines by ELISA: 100 ng/g
Methamphetamine by ELISA: 100 ng/g
Benzoylecgonine (cocaine metabolite) by ELISA: 100 ng/g
Opiates by ELISA: 100 ng/g
Tetrahydrocannabinol carboxylic acid (marijuana metabolite) by ELISA: 20 ng/g
Phencyclidine by ELISA: 20 ng/g
Clinical References: 1. Ostrea EM Jr: Understanding drug testing in the neonate and the role of
meconium analysis. J Perinat Neonatal Nurs 2001 Mar;14(4):61-82; quiz 105-106 2. Ostrea EM Jr, Brady
MJ, Parks PM, et al: Drug screening of meconium in infants of drug-dependent mothers; an alternative to
urine testing. J Pediatr 1989 Sep;115(3):474-477 3. Ahanya SN, Lakshmanan J, Morgan BL, Ross MG:
Meconium passage in utero: mechanisms, consequences, and management. Obstet Gynecol Surv 2005
Jan;60(1):45-56; quiz 73-74
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 730
DBMD Duchenne/Becker Muscular Dystrophy DMD Gene, Large
58125 Deletion and Duplication Analysis
Clinical Information: Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder
characterized initially by proximal muscle weakness beginning before age 5 years. Affected individuals
typically have pseudohypertrophy of the calf muscles and exhibit toe-walking, waddling gait, and the
Gower sign (climbing up the legs when rising from a seated position on the floor). Not only is skeletal
muscle affected in DMD, but also the smooth muscle of the gastrointestinal tract and possibly bladder,
as well as cardiac muscle. Initial symptoms are followed by dramatic progression of weakness leading
to loss of ambulation by age 11 or 12. Death is often caused by cardiac failure or by respiratory failure
before age 30, unless ventilator support is provided. The allelic Becker muscular dystrophy (BMD) has
a similar presentation, although age of onset is later and the clinical course is much milder. Cardiac
involvement can be the only sign and patients are often ambulatory into their thirties. DMD and BMD
are caused by mutations in the DMD gene, which encodes for dystrophin. Approximately 50% to 65%
of patients have intragenic deletions and approximately 5% to 10% have intragenic duplications. Less
frequently, DMD and BMD result from nondeletion and nonduplication mutations, which are not
detected by this assay. Approximately one-third of sporadic cases of DMD/BMD occur due to new
mutations. In sporadic cases, it is possible for the mother of an affected individual to have germline
mosaicism. This means that the germ cells may contain a mutation even if the mutation is not detected
in peripheral blood. In cases of germline mosaicism, which occurs with a frequency of up to 15%,
further offspring are at risk for inheriting a dystrophin mutation.
Useful For: Confirmation of a clinical diagnosis of Duchenne muscular dystrophy (DMD) or Becker
muscular dystrophy (BMD) Distinguishing DMD from BMD in some cases, based on the type of
deletion detected (allows for better prediction of prognosis) Determination of carrier status in family
member at risk for DMD or BMD Prenatal diagnosis of DMD or BMD in at-risk pregnancies
Clinical References: 1. Thompson MW, McInnes RR, Willard HF: Genetics in Medicine. Fifth
edition. Philadelphia, WB Saunders Company, 1991, pp 367-372 2. Desquerre I, Christov C, Mayer M,
et al: Clinical heterogeneity of duchenne muscular dystrophy (DMD): definition of sub-phenotypes and
predictive criteria by long-term follow-up. PLoS One 2009;4(2):e4347 3. Verma S, Anziska Y, Cracco
J: Review of Duchenne muscular dystrophy (DMD) for the pediatricians in the community. Clin Pediatr
(Phila) 2010;49(11):1011-1017
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 731
Interpretation: Detection of IgE antibodies in serum (Class 1 or greater) indicates an increased
likelihood of allergic disease as opposed to other etiologies and defines the allergens that may be
responsible for eliciting signs and symptoms. The level of IgE antibodies in serum varies directly with the
concentration of IgE antibodies expressed as a class score or kU/L.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Reference Values:
<0.35 kU/L
Useful For: Monitoring serum concentration during therapy Evaluating potential toxicity Evaluating
patient compliance
Interpretation: Therapeutic ranges are not well-established, but literature suggests that patients
receiving duloxetine monotherapy for depression responded well when trough concentrations were 60 to
120 ng/mL. Higher levels may be tolerated by individual patients. The therapeutic relevance of this
concentration range to other uses of duloxetine therapy is currently unknown.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 732
Reference Values:
60-120 ng/mL
Clinical References: 1. Westanmo AD, Gayken J, Haight R: Duloxetine: a balanced and selective
norepinephrine- and serotonin-reuptake inhibitor. Am J Health-Syst Pharm 2005;62:2481-2490 2.
Waldschmitt C, Vogel F, Pfuhlmann B, Hiemke C: Duloxetine serum concentrations and clinical
effects. Data from a therapeutic drug monitoring (TDM) survey. Pharmacopsychiatry 2009;42:189-193
Useful For: As aid in differentiation between lobular and ductal neoplasms of the breast
Interpretation: This test includes only technical performance of the stain (no pathologist
interpretation is performed). If diagnostic consultation by a pathologist is required order 70012 /
Pathology Consultation. The positive and negative controls are verified as showing appropriate
immunoreactivity. If a control tissue is not included on the slide, a scanned image of the relevant quality
control tissue is available upon request. Please contact 1-855-516-8404. Interpretation of this test should
be performed in the context of the patient's clinical history and other diagnostic tests by a qualified
pathologist.
Clinical References: 1. Acs G, Lawton TJ, Rebbeck TR, et al: Differential expression of
E-cadherin in lobular and ductal neoplasms of the breast and its biologic and diagnostic implications.
Am J Clin Pathol 2001;115:85-98 2. Mastracci TL, Tjan S, Bane AL, et al: E-cadherin alterations in
atypical lobular hyperplasia and lobular carcinoma In situ of the breast. Modern Pathology
2005;18:741-751 3. Mohammadizadeh F, Ghasemibasir H, Rajabi P, et al: Correlation of E-cadherin
expression and routine immunohistochemistry panel in breast invasive ductal carcinoma. Cancer
Biomark 2009;5(1):1-8 4. Singhai R, Patil VW, Jaiswal SR, et al: E-cadherin as a diagnostic biomarker
in breast cancer. N Am J Med Si 2001;3(5):227-233
Reference Values:
IgG: <1:10
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IgM: <1:10
Reference values apply to all ages.
Reference Values:
IgG: <1:10
IgM: <1:10
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 734
clinical manifestations. In individuals predisposed to develop allergic disease(s), the sequence of
sensitization and clinical manifestations proceed as follows: eczema and respiratory disease (rhinitis and
bronchospasm) in infants and children less than 5 years due to food sensitivity (milk, egg, soy, and wheat
proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 735
infections manifest more rapidly than those of E granulosus, and manifests similar to a rapidly growing,
destructive tumor resulting in abdominal pain and biliary obstruction. Rupture of cysts can produce
fever, urticaria and anaphylactic shock. Diagnosis of echinococcal infections relies on characteristic
finding by ultrasound or other imaging techniques and serologic findings. Fine needle aspirates of cystic
fluid may be performed; however they carry the risk of cyst puncture and fluid leakage which may
potentially lead to severe allergic reactions. Importantly, infected individuals do not shed eggs in stool.
Interpretation: Negative: the absence of antibodies to Echinococcus species suggests that the
individual has not been exposed to this cestode. A single negative result should not be used to rule-out
infection (see Cautions). Equivocal: consider repeat testing on a new serum sample in 1 to 2 weeks.
Positive: results suggest infection with Echinococcus. False positive results may occur in settings of
infection with other helminths, or in patients with chronic immune disorders. Results should be
considered alongside other clinical findings and exposure history.
Reference Values:
Negative
INTERPRETIVE CRITERIA:
< 1:1 Antibody Not Detected
> or = 1:1 Antibody Detected
Diagnosis of infections of the central nervous system is accomplished by demonstrating the presence of
intra-thecally-produced specific antibody. Interpretation of results may be complicated by low antibody
levels found in CSF, passive transfer of antibody from blood, and contamin-ation via bloody taps. The
interpretation of CSF results must consider CSF-serum antibody ratios to the infectious agent.
INTERPRETIVE CRITERIA:
<1:8 Antibody not detected
> or = 1:8 Antibody Detected
Single titers > or = 1:32 are indicative of recent infection. Titers of 1:8 or 1:16 may be indicative of
either past or recent infection, since CF antibody levels persist for only a few months. A four-fold or
greater increase in titer between acute and convalescent specimens confirms the diagnosis. There is
considerable crossreactivity among enteroviruses; however, the highest titer is usually associated with the
infecting serotype.
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ECUMP Eculizumab Monitoring Panel, Serum
64722 Clinical Information: Eculizumab (Soliris, Alexion Pharmaceuticals) is a humanized hybrid
monoclonal antibody (IgG2/IgG4) that blocks complement C5 cleavage, thereby preventing the
activation of the proinflammatory effects of C5a and the cytolytic effects of the membrane attack
complex (MAC) formed by C5b-C9. It is FDA-approved for atypical hemolytic uremic syndrome,(1)
paroxysmal nocturnal hemoglobinuria,(2) and neuromyelitis optica, and also prescribed for other
conditions such as C3 glomerulopathies.(3) The dosing regimen for an average adult may vary from 300
to 1200 mg intravenously every 2 weeks during the maintenance stages, according to the condition for
which the drug is prescribed. Therapy efficacy may be monitored by measuring efficiency of
complement blockade.(4) Eculizumab will affect complement function assays that rely on the formation
of the MAC to generate cell lysis. Although CH50 and sMAC have been recommended for eculizumab
monitoring, the measurement of C5 function and C5 antigen will more specifically indicate the impact
of eculizumab on the complement system blockage and may help guide the next dose of the drug. This
panel measures the pharmacodynamics effects of eculizumab on the complement system.
Reference Values:
C5 COMPLEMENT ANTIGEN
10.6-26.3 mg/dL
C5 COMPLEMENT FUNCTIONAL
29-53 U/mL
Clinical References: 1. Wong EK, Goodship TH, Kavanagh D: Complement therapy in atypical
haemolytic uraemic syndrome (aHUS). Mol Immunol 2013;56:199-212 2. Rother RP, Rollins SA,
Mojcik CF, et al: Discovery and development of the complement inhibitor eculizumab for the treatment
of paroxysmal nocturnal hemoglobinuria. Nat Biotechnol 2007;25:1256-1264 3. Zuber J, Le Quintrec
M, Krid S, et al: Eculizumab for atypical hemolytic uremic syndrome recurrence in renal
transplantation. Am J Transplant 2012;12:3337-3354 4. Volokhina EB, van de Kar NC, Bergseth G, et
al: Sensitive, reliable and easy-performed laboratory monitoring of eculizumab therapy in atypical
hemolytic uremic syndrome. Clin Immunol 2015;160(2):237-243 5. Andreguetto B, Murray D, Snyder
M, et al: The impact of eculizumab in complement assays. Mol Immunol 2015;67:119-120
Useful For: Identifying non-small cell lung cancers that may respond to epidermal growth factor
receptor-tyrosine kinase inhibitor therapies
Clinical References: 1. Sharma SV, Bell DW, Settleman J, Haber DA: Epidermal growth factor
receptor mutations in lung cancer. Nat Rev Cancer 2007;7(3):169-181 2. Gao G, Ren S, Li A, et al:
Epidermal growth factor receptor-tyrosine kinase inhibitor therapy is effective as first-line treatment of
advanced non-small-cell lung cancer with mutated EGFR: a meta-analysis from six phase III randomized
controlled trials. Int J Cancer 2011;131(5):E822-829 3. Mok TS: Personalized medicine in lung cancer:
what we need to know. Nat Rev Clin Oncol 2011;8:661-668
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical utility
of food-specific IgG tests has not been established. These tests can be used in special clinical situations to
select foods for evaluation by diet elimination and challenge in patients who have food-related
complaints. It should be recognized that the presence of food-specific IgG alone cannot be taken as
evidence of food allergy and only indicates immunologic sensitization by the food allergen in question.
This test should only be ordered by physicians who recognize the limitations of the test.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 738
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical utility
of food-specific IgG4 tests has not been clearly established. These tests can be used in special clinical
situations to select foods for evaluation by diet elimination and challenge in patients who have food
related complaints, and to evaluate food allergic patients prior to food challenges. The presence of
food-specific IgG4 alone cannot be taken as evidence of food allergy and only indicated immunologic
sensitization to the food allergen in question.
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 739
High Positive 4 17.50 49.99 Very High Positive 5 50.00 99.99 Very High Positive 6 >99.99
Very High Positive
Reference Values:
<0.35 kU/L
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical utility
of food-specific IgG tests has not been established. These tests can be used in special clinical situations to
select foods for evaluation by diet elimination and challenge in patients who have food-related
complaints. It should be recognized that the presence of food-specific IgG alone cannot be taken as
evidence of food allergy and only indicates immunologic sensitization by the food allergen in question.
This test should only be ordered by physicians who recognize the limitations of the test.
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical utility
of food-specific IgG tests has not been established. These tests can be used in special clinical situations to
select foods for evaluation by diet elimination and challenge in patients who have food-related
complaints. It should be recognized that the presence of food-specific IgG alone cannot be taken as
evidence of food allergy and only indicates immunologic sensitization by the food allergen in question.
This test should only be ordered by physicians who recognize the limitations of the test.
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 741
6 > or =100 Strongly positive Reference values
apply to all ages.
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Interpretation: Serology for IgG may be negative during the acute phase of infection but a diagnostic
titer usually appears by the third week after onset. A positive immunofluorescence assay (titer > or =1:64)
suggests current or previous infection. In general, the higher the titer, the more likely the patient has an
active infection. Four-fold rises in titer also indicate active infection. Previous episodes of ehrlichiosis
may produce a positive serology although antibody levels decline significantly during the year following
infection.
Reference Values:
<1:64
Clinical References: Fishbein DB, Dawson JE, Robinson LE: Human ehrlichiosis in the United
States, 1985 to 1990. Ann Intern Med 1994;120:736-743
Useful For: As an adjunct in the diagnosis of ehrlichiosis and/or in seroepidemiological surveys of the
prevalence of the infection in certain populations Ehrlichiosis is sometimes diagnosed by observing the
organisms in infected WBCs on Giemsa-stained thin blood films of smeared peripheral blood (morulae).
Serology may be useful if the morulae are not seen or if the infection has cleared naturally or following
treatment. Serology may also be useful in the follow-up of documented cases of ehrlichiosis or when
coinfection with other tick- transmitted organisms is suspected. In selected cases, documentation of
infection may be attempted by PCR methods.
Interpretation: A positive immunofluorescence assay (titer >or =1:64) suggests current or previous
infection with Ehrlichia chaffeensis. In general, the higher the titer, the more likely the patient has an
active infection. Four-fold rises in titer also indicate active infection.
Reference Values:
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<1:64
Clinical References: Fishbein DB, Dawson JE, Robinson LE: Human ehrlichiosis in the United
States, 1985 to 1990. Ann Intern Med 1994;120:736-743
Ehrlichia chaffeensis has been identified as the causative agent of Human Monocytic Ehrlichiosis
(HME). Infected individuals produce specific antibodies to E. chaffeensis that can be detected by an
immunofluorescent antibody (IFA) test. Single IgG IFA titers of 1:64 or greater indicate exposure to E.
chaffeensis. A four-fold rise in IgG titers between acute and convalescent samples and/or the presence
of IgM antibody against E. chaffeensis suggest recent or current infection.
Reference Values:
Negative
Clinical References: 1. Bakken JS, Dunler JS: Human granulocytic ehrlichiosis. Clin Infect Dis
2000 Aug;31(2):554-560 2. Dunler JS, Bakken JS: Human ehrlichioses: newly recognized infections
transmitted by ticks. Ann Rev Med 1998;49:201-213 3. Krause PJ, McKay K, Thompson CA, et al:
Disease-specific diagnosis of coinfecting tickborne zoonoses: babesiosis, human granulocytic ehrlichiosis,
and Lyme disease. Clin Infect Dis 1999 May 1;34(9):1184-1191 4. McQuiston JH, Paddock CD, Holman
RC, Childs JE: The human ehrlichioses in the United States. Emerging Infect Dis 1999
Sept-Oct;5(5):635-642 5. Pritt BS, Sloan LM, Johnson DK, et al: Emergence of a new pathogenic
Ehrlichia species, Wisconsin and Minnesota, 2009. N Engl J Med 2011 Aug 4;365(5):422-429 6. Johnson
DK, Schiffman E, Davis JP, et al. Human infection with Ehrlichia muris-like Pathogen, United States,
2007-2013. Emerging Infect Dis 2015; 21(10):1794-99
Reference Values:
Adult Reference Ranges:
Normal pancreatic exocrine function:
Less than 3.5 ng/mL
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sensitization and clinical manifestations proceed as follows: eczema and respiratory disease (rhinitis and
bronchospasm) in infants and children less than 5 years due to food sensitivity (milk, egg, soy, and wheat
proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 745
Useful For: Workup of cases of chronic diarrhea Diagnosis of factitious diarrhea (where patient adds
water to stool to simulate diarrhea)
Reference Values:
No established reference values
Clinical References: 1. Steffer KJ, Santa Ana CA, Cole JA, Fordtran JS: The practical value of
comprehensive stool analysis in detecting the cause of idiopathic chronic diarrhea. Gastroenterol Clin
North Am 2012;41:539-560 2. Sweetser S: Evaluating the patient with diarrhea: A case-based approach.
Mayo Clin Proc 2012;87:596-602 3. Eherer AJ, Fordtran JS: Fecal osmotic gap and pH in experimental
diarrhea of various causes. Gastroenterology 1992;103:545-551 4. Fine KD, Ogunji F, Florio R, et al:
Investigation and diagnosis of diarrhea caused by sodium phosphate. Dig Dis Sci 1998;43(12):2708-2714
5. Phillips S, Donaldson L, Geisler K, et al: Stool composition in factitial diarrhea: a 6-year experience
with stool analysis. Ann Intern Med 1995;123:97-100 6. Casprary WF: Diarrhea associated with
carbohydrate malabsorption. Clin Gastroenterol 1986;15:631-655 7. Ho J, Moyer TP, Phillips SF: Chronic
diarrhea: the role of magnesium. Mayo Clin Proc 1995;70:1091-1092 8. Fine KD, Santa Ana CA,
Fordtran JS: Diagnosis of magnesium-induced diarrhea. N Engl J Med 1991;324:1012-1017
POTASSIUM
<1 year: not established
> or =1 year: 3.6-5.2 mmol/L
CHLORIDE
<1 year: not established
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1-17 years: 102-112 mmol/L
> or =18 years: 98-107 mmol/L
CREATININE
Males
<1 year: not established
1-2 years: 0.10.4mg/dL
3-4 years: 0.1-0.5 mg/dL
5-9 years: 0.20.6 mg/dL
10-11 years: 0.30.7 mg/dL
12-13 years: 0.40.8 mg/dL
14-15 years: 0.50.9 mg/dL
> or =16 years: 0.81.3 mg/dL
Females
<1 year: not established
1-3 years: 0.10.4 mg/dL
4-5 years: 0.20.5 mg/dL
6-8 years: 0.30.6 mg/dL
9-15 years: 0.40.7 mg/dL
> or =16 years: 0.61.1 mg/dL
eGFR
>60 mL/min/1.73 m(2)
Note: eGFR results will not be calculated for patients <17 or >70 years old
BUN
Males
<1 year: not established
1-17 years: 7-20 mg/dL
> or =18 years: 8-24 mg/dL
Females
<12 months: not established
1-17 years: 7-20 mg/dL
> or =18 years: 6-21 mg/dL
BICARBONATE
Males
<1 year: not established
1-2 years: 17-25 mmol/L
3 years: 18-26 mmol/L
4-5 years: 19-27 mmol/L
6-7 years: 20-28 mmol/L
8-17 years: 21-29 mmol/L
> or =18 years: 22-29 mmol/L
Females
<1 year: not established
1-3 years: 18-25 mmol/L
4-5 years: 19-26 mmol/L
6-7 years: 20-27 mmol/L
8-9 years: 21-28 mmol/L
> or =10 years: 22-29 mmol/L
GLUCOSE
<1 year: not established
> or =1 year: 70-140 mg/dL
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4993 Electron Microscopy
Clinical Information: Crucial diagnostic information for the study of human disease may be
provided by transmission and scanning electron microscopy. Often information of a confirmatory nature
or of educational value to the clinician and pathologist can be obtained by this procedure. In recent years,
the technology involved in electron microscopy has progressed to the point where methods have become
standardized and the instrumentation routine. The electron microscope is a fundamental tool in medical
diagnostic and cellular pathobiological investigations, because it is at this instrument's level of resolution
that most structural correlations with function and metabolism are visible.
Useful For: Identifying tumor Diagnosing medical disorders such as storage diseases, cerebral
autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and
primary ciliary dyskinesia
Interpretation: The images and case histories are correlated and interpreted by a pathologist who is an
expert in the field of the suspected diagnoses. Results will be provided by telephone. If requested,
representative images showing diagnostic features will be sent.
Reference Values:
An interpretive report will be provided.
Clinical References: Damjanov I: Ultrastructural Pathology of Human Tumors. St. Albens, VT,
Eden Press, Vol 1, 1979; Vol 2, 1980
Useful For: Monitoring patients with monoclonal gammopathies Urine protein electrophoresis alone is
not considered an adequate screening for monoclonal gammopathies
Interpretation: A characteristic monoclonal band (M-spike) is often found in the urine of patients with
multiple myeloma (MM). The initial identification of an M-spike or an area of restricted migration should
be followed by MPSU / Monoclonal Protein Study, 24 Hour, Urine that includes immunofixation to
identify the immunoglobulin heavy chain and/or light chain. Immunoglobulin heavy chain fragments as
well as free light chains may be seen in the urine of patients with monoclonal gammopathies. The
presence of a monoclonal light chain M-spike of >1 g/24 hours is consistent with a diagnosis of MM or
macroglobulinemia. The presence of a small amount of monoclonal light chain and proteinuria (total
protein >3 g/24 hours) which is predominantly albumin is consistent with amyloidosis (AL) or light chain
deposition disease (LCDD). Because patients with AL and LCDD may have elevated urinary protein
without an identifiable M-spike, urine protein electrophoresis is not considered an adequate "screen" for
the disorder. MPSU / Monoclonal Protein Study, 24 Hour, Urine that includes immunofixation should be
performed if the clinical suspicion is high.
Reference Values:
PROTEIN, TOTAL
<167 mg/24 hours
Reference values have not been established for patients <18 years of age.
Reference values have not been established for patients >83 years of age.
ELECTROPHORESIS, PROTEIN
If protein concentration is abnormal, the following fractions, if present, will be reported as a percent of
the protein, total.
Albumin
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Alpha-1-globulin
Alpha-2-globulin
Beta-globulin
Gamma-globulin
Reference value applies to 24-hour collection. Specimens collected for periods other than 24 hours will
be reported in concentration units.
Clinical References: 1. Kyle, RA, Katzmann, JA, Lust, JA, Dispenzieri A: Clinical indications
and applications of electrophoresis and immunofixation. In Manual of Clinical Laboratory Immunology.
Sixth edition Edited by NR Rose, RG Hamilton, B Detrick: Washington, DC. ASM Press, 2002, pp
66-67 2. Kyle, RA, Katzmann, JA, Lust, JA, Dispernzieri, A: Immunochemical characterization of
immunoglobulins. In Manual of Clinical Laboratory Immunology. Sixth edition, Edited by NR Rose,
RG Hamilton, B Detrick. Washington, DC. ASM Press, 2002, pp 71-91
Useful For: Monitoring patient's body fluid proteins Aiding in the diagnosis of monoclonal
gammopathies, when used in conjunction with immunofixation of the patient's serum Detecting
oligoclonal banding in spinal fluid (the preferred test for detecting oligoclonal bands in spinal fluid is
OLIG / Oligoclonal Banding, Serum and Spinal Fluid)
Reference Values:
Not applicable
Clinical References: Kyle RA, Katzmann JA, Lust JA, Dispenzieri A: Clinical indications and
applications of electrophoresis and immunofixation. Chapter 7. In Manual of Clinical Laboratory
Immunology. Edited by NR Rose, et al. Sixth Edition. Washington, DC. ASM Press, 2002 pp 66-67
Reference Values:
ELECTROPHORESIS, PROTEIN
The following fractions, if present, will be reported as a percent of the total protein.
Albumin
Alpha-1-globulin
Alpha-2-globulin
Beta-globulin
Gamma-globulin
No reference values apply to random urines.
Clinical References: 1. Kyle RA, Katzmann JA, Lust JA, Dispenziei A: Clinical indications and
applications of electrophoresis and immunofixation. In Manual of Clinical Laboratory Immunology. Sixth
edition. Edited by NR Rose, et al. Washington, DC. ASM Press, 2002, pp 66-67 2. Kyle RA, Katzmann
JA, Lust JA, Dispernzieri A: Immunochemical characterization of immunoglobulins. In Manual of
Clinical Laboratory Immunology. Sixth edition. Edited by N.R. Rose, et al. Washington, DC. ASM Press,
2002, pp 71-91
Reference Values:
PROTEIN, TOTAL
> or =1 year: 6.3-7.9 g/dL
Reference values have not been established for patients that are <12 months of age.
PROTEIN ELECTROPHORESIS
Albumin: 3.4-4.7 g/dL
Alpha-1-globulin: 0.1-0.3 g/dL
Alpha-2-globulin: 0.6-1.0 g/dL
Beta-globulin: 0.7-1.2 g/dL
Gamma-globulin: 0.6-1.6 g/dL
An interpretive comment is provided with the report.
Clinical References: Kyle RA, Katzmann JA, Lust JA, Dispenzieri A: Clinical indications and
applications of electrophoresis and immunofixation. In Manual of Clinical Laboratory Immunology.
Sixth edition. Edited by NR Rose, RG Hamilton, B Detrick. Washington DC, ASM Press, 2002 pp
66-70
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 751
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
O-Demethylencainide (ODE):
Reference Range: 100 - 300 ng/mL
3-Methoxy-ODE (MODE):
Reference Range: 60 - 300 ng/mL
10% of patients do not form therapeutic concentrations of the active metabolites, ODE and MODE. In
these patients the recommended range for the encainide concentration is 300 - 1200 ng/mL.
Interpretive Criteria:
<1:1 Antibody Not Detected
>or= 1:1 Antibody Detected
Diagnosis of infections of the central nervous system can be accomplished by demonstrating the
presence of intrathecally-produced specific antibody. However, interpreting results is complicated by low
antibody levels found in CSF, passive transfer of antibody from blood and contamination via bloody taps.
This assay was developed and its performance characteristics determined by Focus Diagnostics. It has
not been cleared or approved by the U.S. Food and Drug Administration. The FDA has determined that
such clearance or approval is not necessary. Performance characteristics refer to the analytical
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 752
performance of the test.
Diagnosis of infections of the central nervous system can be accomplished by demonstrating the
presence of intrathecally-produced specific antibody. Interpreting results may be complicated by low
antibody levels found in CSF, passive transfer of antibody from blood and contamination via bloody taps.
The interpretation of CSF results must consider CSF-serum antibody ratios to the infectious agent.
This assay was developed and its performance characteristics determined by Focus Diagnostics. It has
not been cleared or approved by the U.S. Food and Drug Administration. The FDA has determined that
such clearance or approval is not necessary. Performance characteristics refer to the analytical
performance of the test.
Diagnosis of infections of the central nervous system can be accomplished by demonstrating the
presence of intrathecally-produced specific antibody. Interpretation of results may be complicated by low
antibody levels found in CSF, passive transfer of antibody from blood and contamination via bloody taps.
The interpretation of CSF results must consider CSF-serum antibody ratios to the infectious agent.
This assay was developed and its performance characteristics determined by Focus Diagnostics. It has
not been cleared or approved by the U.S. Food and Drug Administration. The FDA has determined that
such clearance or approval is not necessary. Performance characteristics refer to the analytical
performance of the test.
Diagnosis of infections of the central nervous system can be accomplished by demonstrating the
presence of intrathecally-produced specific antibody. Interpreting results may be complicated by low
antibody levels found in CSF, passive transfer of antibody from blood and contamination via bloody taps.
The interpretation of CSF results must consider CSF-serum antibody ratios to the infectious agent.
This assay was developed and its performance characteristics determined by Focus Diagnostics. It has
not been cleared or approved by the U.S. Food and Drug Administration. The FDA has determined that
such clearance or approval is not necessary. Performance characteristics refer to the analytical
performance of the test.
Interpretive Criteria:
IgG: <1.30 Antibody not detected
1.30 1.49 Equivocal
>=1.50 Antibody detected
West Nile Virus (WNV) IgM is usually detectable in CSF from WNV-infected patients with encephalitis
or meningitis at the time of clinical presentation. Because IgM antibody does not readily cross the
blood-brain barrier, IgM antibody in CSF strongly suggests acute central nervous system infection. WNV
antibody results from CSF should be interpreted with caution. Possible complicating factors include low
levels of antibody found in CSF, passive transfer of antibodies from blood and contamination via bloody
spinal taps. Antibodies induced by other flavivirus infections (e.g. Dengue virus, St. Louis encephalitis
virus) may show cross-reactivity with WNV.
Interpretive Criteria:
< or = 1.00 Antibody not detected
>1.00 Antibody detected
Detection of HSV type-specific IgG in CSF may indicate central nervous system (CNS) infection by that
HSV type. However, interpretation of results may be complicated by a number of factors, including low
antibody levels found in CSF, passive transfer of antibody across the blood-brain barrier, and serum
contamination of CSF during CSF collection. PCR detection of type-specific HSV DNA in CSF is the
preferred method for identifying HSV CNS infections.
Herpes Simplex Virus 1/2 Antibody (IgM), IFA with Reflex to Titer, CSF
The IFA procedure for measuring IgM antibodies to HSV 1 and HSV 2 detects both type-common and
type-specific HSV antibodies. Thus, IgM reactivity to both HSV 1 and HSV 2 may represent
cross-reactive HSV antibodies rather than exposure to both HSV 1 and HSV 2.
Diagnosis of central nervous system infections can be accomplished by demonstrating the presence of
intrathecally-produced specific antibody. Interpreting results may be complicated by low antibody levels
found in CSF, passive transfer of antibody from blood and contamination via bloody taps. The
interpretation of CSF results must consider CSF-serum antibody ratios to the infectious agent.
This test was developed and its characteristics have been determined by Focus Diagnostics. Performance
characteristics refer to the analytical performance of the test.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 754
molecules, and RNA-regulatory proteins in the cytoplasm and nucleus of neurons (GAD65, CRMP-5,
ANNA-1, and ANNA-2). Importantly, autoimmune encephalopathies are reversible. Misdiagnosed as a
progressive (currently irreversible) neurodegenerative condition is not uncommon and has devastating
consequences for the patient. Clinicians must consider the possibility of an autoimmune etiology in the
differential diagnoses of encephalopathy. For example, a potentially reversible disorder justifies a trial of
immunotherapy for the detection of neural autoantibodies in patients presenting with symptoms of
personality change, executive dysfunction, and psychiatric manifestations. A triad of clues helps to
identifying patients with an autoimmune encephalopathy: 1) clinical presentation (subacute symptoms
onset rapidly progressive course and fluctuating symptoms) and radiological findings consistent with
inflammation, 2) detection of neural autoantibodies in serum or cerebrospinal fluid (CSF), and 3)
favorable response to a trial of immunotherapy. Detection of neural autoantibodies in serum or CSF
informs the physician of a likely autoimmune etiology, and may heighten suspicion for a paraneoplastic
basis and guide the search for cancer. Neurological accompaniments of neural autoantibodies are
generally not syndromic, but diverse and multifocal. For example, neuronal voltage-gated potassium
channel (VGKC)-complex antibodies were initially considered specific for autoimmune limbic
encephalitis or disorders of peripheral nerve hyperexcitability. However, more diverse presentations are
now recognized, including rapidly progressive cognitive decline mimicking frontotemporal dementia and
Creutzfeldt-Jakob disease. Comprehensive antibody testing is more informative than selective testing for
1 or 2 neural antibodies. Some antibodies strongly predict an underlying cancer. For example; small-cell
lung carcinoma (antineuronal nuclear antibody-type 1, ANNA-1; collapsin response-mediator protein-5
neuronal, CRMP-5-IgG), ovarian teratoma (N-methyl-D-aspartate receptor, NMDA-R), and thymoma
(CRMP-5 IgG). An individual patients profile autoantibody may be informative for a specific cancer
type. For example, detection of muscle acetylcholine receptor (AChR) binding, alpha 3 ganglionic AChR,
and CRMP 5 IgG in a patient presenting with encephalopathy suggests thymoma. When an associated
tumor is found, its resection or ablation optimizes the neurological outcome. Testing of CSF for
autoantibodies is particularly helpful when serum testing is negative. Simultaneous testing of serum and
CSF is recommended for NMDA-R antibody, because CSF is usually more informative.
Interpretation: Neuronal, glial, and muscle autoantibodies are valuable serological markers of
autoimmune encephalopathy and of a patient's immune response to cancer. These autoantibodies are
usually accompanied by subacute neurological symptoms and signs are not found in healthy subjects. It
is not uncommon for more than 1 of the following autoantibody specificities to be detected in patients
with an autoimmune encephalopathy. -Plasma membrane autoantibodies: voltage-gated potassium
channel complex, N-methyl-D-aspartate (NMDA) receptor; 2-amino-3-(5-methyl-3-oxo-1,2-
oxazol-4-yl) propanoic acid (AMPA) receptor; gamma-amino butyric acid (GABA-B) receptor;
neuronal Ach receptor. These are all potential effectors of neurological dysfunction -Neuronal nuclear
autoantibodies, type 1 (ANNA-1), type 2 (ANNA-2), or type 3 (ANNA-3). -Neuronal or muscle
cytoplasmic antibodies: amphiphysin, Purkinje cell antibodies (PCA-1) and PCA-2, CRMP-5, GA65, or
striational.
Reference Values:
NEURONAL NUCLEAR ANTIBODIES
Antineuronal Nuclear Ab, Type 1 (ANNA-1)
<1:240
Antineuronal Nuclear Ab, Type 2 (ANNA-2)
<1:240
Antineuronal Nuclear Ab, Type 3 (ANNA-3)
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 755
<1:240
Anti-Glial/Neuronal Nuclear Ab, Type 1 (AGNA-1)
<1:240
WESTERN BLOT
Paraneoplastic Western Blot
Negative
CRMP-5-IgG Western Blot
Negative
Amphiphysin Western Blot
Negative
Clinical References: 1. McKeon A, Lennon, VA, Pittock, SJ: Immunotherapy responsive dementias
and encephalopathies. Continuum Lifelong Learning Neurol 2010;16(2):80-101 2. Lucchinetti CF,
Kimmel DW, Lennon VA: Paraneoplastic and oncological profiles of patients seropositive for type 1
anti-neuronal nuclear autoantibodies. Neurology 1998;50:652-657 3. Pittock SJ, Yoshikawa H, Ahlskog
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 756
JE, et al: Glutamic acid decarboxylase autoimmunity with brainstem, extrapyramidal and spinal cord
dysfunction. Mayo Clin Proc 2006;81:1207-1214 4. Lancaster E, Martinez-Hernandez E, Dalmau J:
Encephalitis and antibodies to synaptic and neuronal cell surface proteins. Neurology 2011;77(2):179-189
5. Klein CJ, Lennon VA, Aston PA, et al: Insights from LGI1 and CASPR2 potassium channel complex
autoantibody subtyping. JAMA Neurol 2013;70(2):229-234
Interpretation: Neuronal, glial, and muscle autoantibodies are valuable serological markers of
autoimmune encephalopathy and of a patient's immune response to cancer. These autoantibodies are
usually accompanied by subacute neurological symptoms and signs are not found in healthy subjects. It is
not uncommon for more than 1 of the following autoantibody specificities to be detected in patients with
an autoimmune encephalopathy. -Plasma membrane autoantibodies: These are all potential effectors of
neurological dysfunction: neuronal voltage-gated potassium channel (VGKC)-complex,
N-methyl-D-aspartate (NMDA) receptor; 2-amino-3-(5-methyl-3-oxo-1,2- oxazol-4-yl) propanoic acid
(AMPA) receptor; gamma-amino butyric acid (GABA-B) receptor; neuronal ACh receptor -Neuronal
nuclear autoantibodies: type 1 (ANNA-1), type 2 (ANNA-2), or type 3 (ANNA-3) -Neuronal or muscle
cytoplasmic antibodies: amphiphysin, Purkinje cell antibodies (PCA-1 and PCA-2), CRMP-5, GA65, or
striational.
Reference Values:
NEURONAL NUCLEAR ANTIBODIES
Antineuronal Nuclear Antibody-Type 1 (ANNA-1)
<1:2
Antineuronal Nuclear Antibody-Type 2 (ANNA-2)
<1:2
Antineuronal Nuclear Antibody-Type 3 (ANNA-3)
<1:2
Anti-Glial/Neuronal Nuclear Antibody-Type 1 (AGNA-1)
<1:2
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 758
WESTERN BLOT
Paraneoplastic Autoantibody, Western Blot Confirmation
Negative
Collapsin Response-Mediator Protein-5-IGG (CRMP-5-IGG) Western Blot
Negative
Amphiphysin Antibody Western Blot
Negative
Useful For: Supporting the diagnosis of endometrial stromal tumors when used in conjunction with
an anatomic pathology consultation
Interpretation: A neoplastic clone is detected when the percent of cells with an abnormality exceeds
the normal cutoff for any given probe. Detection of an abnormal clone likely indicates a diagnosis of an
endometrial stromal tumor of various subtypes. The absence of an abnormal clone does not rule out the
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 759
presence of a neoplastic disorder.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Koontz J, Soreng AL, Nucci M, et al: Frequent fusion of the JAZF1 and
JJAZ1 genes in endometrial stromal tumors. Proc Natl Acad Sci USA 2001;98(11):6348-6353 2. Nucci R,
Harburger D, Koontz J, et al: Molecular analysis of the JAZF1-JJAZ1 gene fusion by RT-PCR and
fluorescence in situ hybridization in endometrial stromal neoplasms. Am J Surg Pathol 2007;31(1):65-70
3. Huang HY, Ladanyi M, Soslow RA: Molecular detection of JAZF1-JJAZ1 gene fusion in endometrial
stromal neoplasms with classic and variant histology-evidence for genetic heterogeneity. Am J Surg
Pathol 2004;28(2):224-232 4. Chiang S, Ali R, Melnyk N, et al: Frequency of known gene
rearrangements in endometrial stromal tumors. Am J Surg Pathol 2011;35(9):1364-1372 5. Lee CH,
Marino-Enriquez A, Ou W, et al: The clinicopathologic features of YWHAE-FAM22 endometrial stromal
sarcomas: A histologically high-grade and clinically aggressive tumor. Am J Surg Pathol
2012;36(5):641-653 6. Panagopoulos I, Mertens F, Griffin CA, et al: An endometrial stromal sarcoma cell
line with the JAZF1/PHF1 chimera. Cancer Genet Cytogenet 2008 Sep;185(2):74-77 7. Lee CH, Ou WB,
Marino-Enriquez A, et al: 14-3-3 fusion oncogenes in high-grade endometrial stromal sarcoma. Proc Natl
Acad Sci U S A 2012;109(3):929-934 8. Micci F, Panagopoulos I, Bjerkehagen B, et al: Consistent
rearrangement of chromosomal band 6p21 with generation of fusion genes JAZF1/PHF1 and EPC1/PHF1
in endometrial stromal sarcoma. Cancer Res 2006;66(1):107-112 9. Gebre-Medhin S, Nord KH, Moller E,
et al: Recurrent rearrangement of the PHF1 gene in ossifying fibromyxoid tumors. Am J Pathol
2012;181(3):1069-1077
Useful For: Evaluation of: -Cardiac allograft rejection -Cardiomyopathies -Myocarditis -Idiopathic
arrhythmias -Idiopathic chest pain -Anthracycline cardiotoxicity -Secondary heart disease (amyloidosis,
sarcoidosis, hemochromatosis, storage diseases, and neoplastic diseases)
Reference Values:
Abnormalities will be compared to reported reference values.
Clinical References: Edwards WD, Holmes DR Jr: Transvenous endomyocardial biopsy. In Mayo
Clinic Practice of Cardiology: Fundamentals and Practice. 3rd edition. Edited by ER Giuliani, BJ Gersh,
MD McGooh, et al. St. Louis, MO, Mosby-Yearbook, 1996, pp 672-688
Reference Values:
Negative: <1:2.5 titer
Positive: > or = 1:2.5 titer
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 760
EMAT Endomysial (IgA), Titer, Serum
65091 Reference Values:
Only orderable as a reflex. For more information see EMA / Endomysial Antibodies (IgA), Serum.
Negative
Useful For: Diagnosis of dermatitis herpetiformis and celiac disease Monitoring adherence to
gluten-free diet in patients with dermatitis herpetiformis and celiac disease Because of the high
specificity of endomysial antibodies for celiac disease, the test may obviate the need for multiple small
bowel biopsies to verify the diagnosis. This may be particularly advantageous in the pediatric
population, including the evaluation of children with failure to thrive.
Interpretation: The finding of IgA-endomysial antibodies (EMA) is highly specific for dermatitis
herpetiformis or celiac disease. The titer of IgA-EMA generally correlates with the severity of
gluten-sensitive enteropathy. If patients strictly adhere to a gluten-free diet, the titer of IgA-EMA should
begin to decrease within 6 to 12 months of onset of dietary therapy. Occasionally, the staining results
cannot be reliably interpreted as positive or negative because of strong smooth muscle staining, weak
EMA staining or other factors; in this case, the results will be recorded as "indeterminate." In this
setting, further testing with measurement of TTGA / Tissue Transglutaminase (tTG) Antibody, IgA,
Serum and IGA / Immunoglobulin A (IgA), Serum levels are recommended.
Reference Values:
Negative in normal individuals; also negative in dermatitis herpetiformis or celiac disease patients
adhering to gluten-free diet. See Results of IF Testing in Cutaneous Immunofluorescence Testing in
Special Instructions.
Clinical References: 1. Peters MS, McEvoy MT: IgA antiendomysial antibodies in dermatitis
herpetiformis. J Am Acad Dermatol 1989;21:1225-1231 2. Chorzelski TP, Buetner EH, Sulej J, et al:
IgA anti-endomysium antibody: a new immunological marker of dermatitis herpetiformis and coeliac
disease. Br J Dermatol 1984;111:395-402 3. Kapuscinska A, Zalewski T, Chorzelski TP, et al: Disease
specificity and dynamics of changes in IgA class anti-endomysial antibodies in celiac disease. J Pediatr
Gastroenterol Nutr1984;6:529-534
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: As an adjunct in the diagnosis of extraintestinal amebiasis, especially liver abscess
Serology may be particularly useful in supporting the diagnosis of amebic liver abscess in patients
without a definite history of intestinal amebiasis and who have not spent substantial periods of time in
endemic areas
Interpretation: A positive result suggests current or previous infection with Entamoeba histolytica.
Since pathogenic and nonpathogenic species of Entamoeba cannot be differentiated microscopically,
some authorities believe a positive serology indicates the presence of the pathogenic species (ie,
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 762
Entamoeba histolytica).
Reference Values:
Expected values: negative
The Entamoeba histolytica antigen EIA test detects only the antigen of the pathogenic E. histolytica;
the non-pathogenic E. dispar is not detected.
Useful For: Determining whether a bacterial enteric pathogen is the cause of diarrhea May be helpful
in identifying the source of the infectious agent (eg, dairy products, poultry, water, or meat)
Clinical References: 1. York MK, Rodrigues-Wong P, Church L: Fecal Culture for Aerobic
Pathogens of Gastroenteritis, Clinical Microbiology Procedures Handbook, Third edition. Washington,
DC, ASM Press, 2010, Section 3.8.1 2. Jerris RC, Fields PI, Nicholson MA: Fecal Culture for
Campylobacter and Related Organisms, Clinical Microbiology Procedures Handbook, Third edition.
Washington, DC, ASM Press, 2010, Section 3.8.2 3. DuPont H.L: Persistent Diarrhea: A Clinical
Review. JAMA, June 28, 2016;315(24):2712-2723. doi:10.1001/jama.2016.7833
INTERPRETIVE CRITERIA:
<1:1 Antibody Not Detected
> or = 1:1 Antibody Detected
Diagnosis of infections of the central nervous system is accomplished by demonstrating the presence
of intrathecally-produced specific antibody. Interpretation of results may be complicated by low
antibody levels found in CSF, passive transfer of antibody from blood, and contamination via bloody
taps. The interpretation of CSF results must consider CSF-serum antibody ratios to the infectious agent.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 763
FEPCF Enterovirus Panel, CF, Serum
57828 Reference Values:
ENTEROVIRUS PANEL, CF, SERUM
REFERENCE RANGE: <1:8
Single titers of > or = 1:32 are indicative of recent infection. Titers of 1:8 or 1:16 may be indicative of
either past or recent infection, since CF antibody levels persist for only a few months. A four-fold or
greater increase in titer between acute and convalescent specimens confirms the diagnosis. There is
considerable crossreactivity among enteroviruses; however, the highest titer is usually associated with the
infecting serotype.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 764
including types 22 and 23, which are now classified as parechoviruses), coxsackievirus A (23 types), and
coxsackievirus B (6 types). However, genomic studies have demonstrated that there is significant overlap
in the biological characteristics of different serotypes and, more recently, isolated enteroviruses are now
named with consecutive numbers (eg, EV68, EV69). The normal site of enterovirus replication is the
gastrointestinal tract where the infection is typically subclinical. However, in a proportion of cases, the
virus spreads to other organs, causing systemic manifestations, including mild respiratory disease (eg,
common cold); conjunctivitis; hand, foot, and mouth disease; aseptic meningitis; myocarditis; and acute
flaccid paralysis. Collectively, enteroviruses are the most common cause of upper respiratory tract disease
in children. In addition, the enteroviruses are the most common cause of central nervous system (CNS)
disease; they account for almost all viruses recovered in culture from spinal fluid. Differentiation of
enteroviruses from other viruses and bacteria that cause CNS disease is important for the appropriate
medical management of these patients. Traditional cell culture methods require 6 days, on average, for
enterovirus detection. In comparison, real-time PCR allows same-day detection. Detection of enterovirus
nucleic acid by PCR is also the most sensitive diagnostic method for the diagnosis of CNS infection
caused by these viruses.
Reference Values:
None seen
Clinical References: 1. Hansel FK: In Clinical Allergy. CV Mosby Co. St. Louis, 1953 2. Brunzel
NA: Chapter 8: Microscopic Examination of Urine Sediment. In Fundamentals of Urine and Body
Fluids Analysis. Third edition. Edited by NA Brunzel. Elsevier Saunders. St. Louis, MO, 2012, pp
171-172
Reference Values:
<0.35 kU/L
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 766
ENFD Epidermal Nerve Fiber Density Consult
60463 Clinical Information: Small fiber peripheral neuropathy is a common neurological complaint and a
frequent source of morbidity in many patient populations. Direct investigation of small fiber
involvement has been limited as most classical techniques such as electromyography (EMG), nerve
conduction studies (NCS), and nerve biopsy, focus on large diameter nerve fibers and may be normal in
patients with small fiber neuropathies. The advent of epidermal skin biopsies and PGP 9.5
immunohistochemistry allows the direct visualization and morphologic assessment of small sensory
fibers innervating the skin.(1) Assessment of intraepidermal nerve fiber density (IENFD) has been used
to reliably demonstrate pathologic abnormalities in small fiber neuropathy of various etiologies
including diabetes, HIV, systemic lupus erythematosus, and neurosarcoidosis. Further, the technique has
been validated, shown to have acceptable sensitivity and specificity, and is minimally invasive. The
publication of normative data for commonly tested sites such as the distal and proximal legs and arms
permits direct comparison of patients to age- and sex-matched controls facilitating localization and
diagnosis.(2-4) Based on class 1 evidence and American Medical Association CPT code review process
acceptance, IENFD measurements are now an accepted investigational method in the workup of
polyneuropathy, including the characterization and diagnosis of varieties of length-dependent small
fiber polyneuropathies. IEFND measurements have been incorporated in recent practice guidelines
published by the American Academy of Neurology and the European Federation of Neurological
Science.(5,6)
Reference Values:
A consultative report will be provided.
Clinical References: 1. Lauria G, Lombardi R, Camozzi F, Devigili G: Skin biopsy for the
diagnosis of peripheral neuropathy. Histopathology 2009;54(3):273-285 2. McArthur JC, Stocks EA,
Hauer P, et al: Epidermal nerve fiber density: normative reference range and diagnostic efficiency. Arch
Neurol 1998;55(12):1513-1520 3. Goransson LG, Mellgren SI, Lindal S, Omdal R: The effect of age
and gender on epidermal nerve fiber density. Neurology 2004;62(5):774-777 4. Umapathi T, Tan WL,
Tan NC, Chan YH: Determinants of epidermal nerve fiber density in normal individuals. Muscle Nerve
2006;33(6):742-746 5. Lauria G, Cornblath DR, Johansson O, et al: EFNS guidelines on the use of skin
biopsy in the diagnosis of peripheral neuropathy. Eur J Neurol 2005;12(10):747-758 6. England JD,
Gronseth GS, Franklin G, et al: Practice parameter: evaluation of distal symmetric polyneuropathy: role
of autonomic testing, nerve biopsy, and skin biopsy (an evidence-based review). Report of the
American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic
Medicine, and American Academy of Physical Medicine and Rehabilitation. Neurology
2009;72(2):177-184 7. England JD, Gronseth GS, Franklin G, et al: Evaluation of distal symmetric
polyneuropathy: the role of autonomic testing, nerve biopsy, and skin biopsy (an evidence-based
review). Muscle Nerve 2009 Jan;39(1):106-115 8. Engelstad JK, Taylor SW, Witt LV, et al: Epidermal
nerve fibers. Confidence intervals and continuous measures with nerve conduction. Neurology
2012;79:2187-2193
Reference Values:
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 767
<0.35 kU/L
Useful For: Investigating new onset cryptogenic epilepsy with incomplete seizure control and duration
of <2 years Investigating new onset cryptogenic epilepsy plus 1 or more of the following
accompaniments: -Psychiatric accompaniments (psychosis, hallucinations) -Movement disorder
(myoclonus, tremor, dyskinesias) -Headache -Cognitive impairment/encephalopathy -Autoimmune
stigmata (personal history or family history or signs of diabetes mellitus, thyroid disorder, vitiligo,
premature graying of hair, myasthenia gravis, rheumatoid arthritis, systemic lupus erythematosus,
idiopathic adrenocortical insufficiency), or multiple sclerosis -History of cancer -Smoking history (20+
pack years) or other cancer risk factors -Investigating seizures occurring within the context of a subacute
multifocal neurological disorder without obvious cause, especially in a patient with past or family history
of cancer -A rising autoantibody titer in a previously seropositive patient suggests cancer recurrence
Interpretation: Antibodies specific for neuronal, glial, or muscle proteins are valuable serological
markers of autoimmune epilepsy and of a patient's immune response to cancer. These autoantibodies are
not found in healthy subjects, and are usually accompanied by subacute neurological symptoms and signs.
It is not uncommon for more than 1 of the following autoantibodies to be detected in patients with
autoimmune epilepsy. -Plasma membrane antibodies (N-methyl-D-aspartate: NMDA receptor;
2-amino-3-[5-methyl-3-oxo-1,2- oxazol-4-yl] propanoic acid: AMPA receptor; gamma-amino butyric
acid: GABA-B receptor). These autoantibodies are all potential effectors of dysfunction. -Neuronal
nuclear autoantibody, type 1 (ANNA-1) or type 3 (ANNA-3). -Neuronal or muscle cytoplasmic antibodies
(amphiphysin, Purkinje cell antibody-type 2: PCA-2, collapsin response-mediator protein-5 neuronal:
CRMP-5-IgG, or glutamic acid decarboxylase: GAD65 antibody).
Reference Values:
NEURONAL NUCLEAR ANTIBODIES
Antineuronal Nuclear Ab, Type 1 (ANNA-1)
<1:240
Antineuronal Nuclear Ab, Type 2 (ANNA-2)
<1:240
Antineuronal Nuclear Ab, Type 3 (ANNA-3)
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 768
<1:240
Anti-Glial/Neuronal Nuclear Ab, Type 1 (AGNA-1)
<1:240
WESTERN BLOT
Paraneoplastic Western Blot
Negative
CRMP-5-IgG Western Blot
Negative
Amphiphysin Western Blot
Negative
Clinical References: 1. Quek AM, Britton JW, McKeon A, et al: Autoimmune epilepsy: clinical
characteristics and response to immunotherapy. Arch Neurol 2012 May;69(5):582-593 2. Yu Z, Kryzer
TJ, Griesmann GE, et al: CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related
autoimmunity. Ann Neurol 2001 Feb;49(2):146-154 *Accompanying Editorial: 49:141-142 3. Pittock
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 769
SJ, Yoshikawa H, Ahlskog JE, et al: Glutamic acid decarboxylase autoimmunity with brainstem,
extrapyramidal and spinal cord dysfunction. Mayo Clin Proc 2006;81:1207-1214 4. Klein CJ, Lennon
VA, Aston PA, et al: Insights from LGI1 and CASPR2 potassium channel complex autoantibody
subtyping. JAMA Neurol 2013;70(2):229-234 5. Lancaster E, Martinez-Hernandez E, Dalmau J:
Encephalitis and antibodies to synaptic and neuronal cell surface proteins. Neurology
2011;77(2):179-189
Useful For: Investigating new onset cryptogenic epilepsy with incomplete seizure control and duration
of <2 years Investigating new onset cryptogenic epilepsy plus 1 or more of the following
accompaniments: -Psychiatric accompaniments (psychosis, hallucinations) -Movement disorder
(myoclonus, tremor, dyskinesias) -Headache -Cognitive impairment/encephalopathy -Autoimmune
stigmata (personal history or family history or signs of diabetes mellitus, thyroid disorder, vitiligo,
premature graying of hair, myasthenia gravis, rheumatoid arthritis, systemic lupus erythematosus,
idiopathic adrenocortical insufficiency) or multiple sclerosis" -History of cancer -Smoking history
(20+ pack years) or other cancer risk factors -Investigating seizures occurring within the context of a
subacute multifocal neurological disorder without -obvious cause, especially in a patient with past or
family history of cancer
Interpretation: Antibodies specific for neuronal, glial, or muscle proteins are valuable serological
markers of autoimmune epilepsy and of a patient's immune response to cancer. These autoantibodies are
not found in healthy subjects, and are usually accompanied by subacute neurological symptoms and signs.
It is not uncommon for more than 1 of the following autoantibodies to be detected in patients with
autoimmune epilepsy: -Plasma membrane antibodies (N-methyl-D-aspartate [NMDA] receptor;
2-amino-3-[5-methyl-3-oxo-1,2-oxazol-4-yl] propanoic acid [AMPA] receptor; gamma-amino butyric
acid [GABA-B] receptor). These autoantibodies are all potential effectors of dysfunction. -Neuronal
nuclear autoantibody, type 1 (ANNA-1) or type 3 (ANNA-3). -Neuronal or muscle cytoplasmic antibodies
(amphiphysin, Purkinje cell antibody-type 2 [PCA-2], collapsin response-mediator protein-5 neuronal
[CRMP-5-IgG], or glutamic acid decarboxylase [GAD65] antibody). A rising autoantibody titer in a
previously seropositive patient suggests cancer recurrence.
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Reference Values:
NEURONAL NUCLEAR ANTIBODIES
Antineuronal Nuclear Antibody-Type 1 (ANNA-1)
<1:2
Antineuronal Nuclear Antibody-Type 2 (ANNA-2)
<1:2
Antineuronal Nuclear Antibody-Type 3 (ANNA-3)
<1:2
Anti-Glial/Neuronal Nuclear Antibody-Type 1 (AGNA-1)
<1:2
WESTERN BLOT
Paraneoplastic Autoantibody, Western Blot Confirmation
Negative
Collapsin Response-Mediator Protein-5-IGG (CRMP-5-IGG) Western Blot
Negative
Amphiphysin Antibody Western Blot
Negative
Clinical References: 1. Quek AL, Britton JW, McKeon A, et al: Autoimmune epilepsy: clinical
characteristics and response to immunotherapy. Arch Neurol 2012 May;69(5):582-593 2. Yu Z, Kryzer
TJ, Griesmann GE, et al: CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related
autoimmunity. Ann Neurol 2001 Feb;49(2):146-154; Editorial: 49:141-142 3. Pittock SJ, Yoshikawa H,
Ahlskog JE, et al: Glutamic acid decarboxylase autoimmunity with brainstem, extrapyramidal and
spinal cord dysfunction. Mayo Clin Proc 2006;81:1207-1214 4. Klein CJ, Lennon VA, Aston PA, et al:
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 771
Insights from LGI1 and CASPR2 potassium channel complex autoantibody subtyping. JAMA Neurol
2013;70(2):229-234 5. Lancaster E, Martinez-Hernandez E, Dalmau J: Encephalitis and antibodies to
synaptic and neuronal cell surface proteins. Neurology 2011;77(2):179-189
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. New York,
WB Saunders Company, 2007, Part VI, pp 961-971
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clinical manifestations. In individuals predisposed to develop allergic disease(s), the sequence of
sensitization and clinical manifestations proceed as follows: eczema and respiratory disease (rhinitis and
bronchospasm) in infants and children less than 5 years due to food sensitivity (milk, egg, soy, and wheat
proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. New York,
WB Saunders Company, 2007, Part VI, pp 961-971
Useful For: An aid in recognizing epithelial derivation of poorly differentiated malignant tumors
Interpretation: This test includes only technical performance of the stain (no pathologist
interpretation is performed). If diagnostic consultation by a pathologist is required order 70012 /
Pathology Consultation. The positive and negative controls are verified as showing appropriate
immunoreactivity. If a control tissue is not included on the slide, a scanned image of the relevant quality
control tissue is available upon request. Please contact 1-855-516-8404. Interpretation of this test should
be performed in the context of the patient's clinical history and other diagnostic tests by a qualified
pathologist.
Useful For: An aid in the identification of Epstein Barr virus infection in normal, inflammatory, and
neoplastic tissues
Useful For: An aid in the identification of Epstein Barr virus infection in normal, inflammatory, and
neoplastic tissues
Interpretation: This test includes only technical performance of the stain (no pathologist interpretation
is performed). If diagnostic consultation by a pathologist is required order 70012 / Pathology
Consultation. The positive and negative controls are verified as showing appropriate immunoreactivity. If
a control tissue is not included on the slide, a scanned image of the relevant quality control tissue is
available upon request. Please contact 1-855-516-8404. Interpretation of this test should be performed in
the context of the patient's clinical history and other diagnostic tests by a qualified pathologist.
Clinical References: 1. Araujo I, Foss HD, Hummel M, et al: Frequent expansion of Epstein-Barr
virus (EBV) infected cells in germinal centres of tonsils from an area with a high incidence of
EBV-associated lymphoma. J Pathol 1999;187:326-330 2. Gulley ML, Glaser SL, Craig FE, et al:
Guidelines for interpreting EBER in situ hybridization and LMP1 immunohistochemical tests for
detecting Epstein-Barr virus in Hodgkin lymphoma. Am J Clin Pathol 2002;117:259-267 3. Mehraein Y,
Lennerz C, Ehlhardt S, et al: Latent Epstein-Barr virus (EBV) infection and cytomegalovirus (CMV)
infection in synovial tissue of autoimmune chronic arthritis determined by RNA-and DNA-in situ
hybridization. Modern Pathology 2004;17:781-789 4. Anagnostopoulos I, Hummel M, Falini B, et al:
Epstein-Barr virus infection of monocytoid B-cell proliferates-An early feature of primary viral infection?
Am J Surg Pathol 2005;29:595-601
Interpretation: The test has 3 components: viral capsid antigen (VCA) IgG, VCA IgM, and
Epstein-Barr nuclear antigen (EBNA). Presence of VCA IgM antibodies indicates recent primary
infection with Epstein-Barr virus (EBV). The presence of VCA IgG antibodies indicates infection
sometime in the past. Antibodies to EBNA develop 6 to 8 weeks after primary infection and are
detectable for life. Over 90% of the normal adult population has IgG class antibodies to VCA and
EBNA. Few patients who have been infected with EBV will fail to develop antibodies to the EBNA
(approximately 5%-10%). Possible Results VCA IgG VCA IgM EBNA IgG Interpretation - - - No
previous exposure + + - Recent infection + - + Past infection + - - See note* + + + Past infection
*Results indicate infection with EBV at some time (VCA IgG positive). However, the time of the
infection cannot be predicted (ie, recent or past) since antibodies to EBNA usually develop after
primary infection (recent) or, alternatively, approximately 5% to 10% of patients with EBV never
develop antibodies to EBNA (past).
Reference Values:
Epstein-Barr Virus (EBV) VIRAL CAPSID ANTIGEN (VCA) IgM ANTIBODY
Negative
Useful For: Detection of Epstein-Barr virus encoded RNA (EBER) in the diagnosis of
EBV-associated conditions
Interpretation: This test, when not accompanied by a pathology consultation request, will be
answered as either positive or negative. If additional interpretation or analysis is needed, request 70012 /
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 775
Pathology Consultation along with this test.
Clinical References: 1. Wu TC, Mann RB, Epstein JI, et al: Abundant expression of EBER1 small
nuclear RNA in nasopharyngeal carcinoma. A morphologically distinctive target for detection of
Epstein-Barr virus in formalin-fixed paraffin-embedded carcinoma specimens. Am J Pathol
1991;138:1461-1469 2. Randhawa PS, Jaffe R, Demetris AJ, et al: The systemic distribution of
Epstein-Barr virus genomes in fatal post-transplantation lymphoproliferative disorders. An in situ
hybridization study. Am J Pathol 1991;138:1027-1033 3. Chang KL, Chen YY, Shibata D, Weiss LM:
Description of an in situ hybridization methodology for detection of Epstein-Barr Virus RNA in
paraffin-embedded tissues, with a survey of normal and neoplastic tissues. Diagn Mol Pathol
1992;1:246-255
Useful For: A third-order test in the diagnosis of infectious mononucleosis, especially in situations
when initial testing results (heterophile antibody test) are negative and follow-up testing (viral capsid
antigen: VCA IgG, VCA IgM, and Epstein-Barr nuclear antigen) yields inconclusive results aiding in the
diagnosis of type 2 or type 3 nasopharyngeal carcinoma
Interpretation: The presence of antibody to the early antigen (EA) of Epstein-Barr virus (EBV)
indicates that EBV is actively replicating. Generally, this antibody can only be detected during active
EBV infection, such as in patients with infectious mononucleosis. Clinical studies have indicated that
patients who have chronic active or reactivated EBV infection commonly have elevated levels of
IgG-class antibodies to the EA of EBV. IgG antibody specific for the diffuse early antigen of EBV is
often found in patients with nasopharyngeal carcinoma (NPC). Of patients with type 2 or 3 NPC (World
Health Organization classification), 94% and 83% respectively, have positive-antibody responses to EA.
Only 35% of patients with type 1 NPC have a positive response. The specificity of the test is such that
82% to 91% of healthy blood donor controls and patients who do not have NPC have negative responses
(9%-18% false-positives). Although this level of specificity is useful for diagnostic purposes, the
false-positive rate indicates that the test is not useful for NPC screening.
Reference Values:
Negative
Clinical References: 1. Fields BN, Knipe DM: Epstein-Barr virus. In Fields Virology. Fourth
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 776
edition. Edited by BN Fields, DM Knipe, PM Howley. Philadelphia, Lippincott Williams and Wilkins,
2001 2. Lennette ET: Epstein-Barr virus. In Manual of Clinical Microbiology. Sixth edition. Edited by PR
Murray, EJ Baron, MA Pfaller, et al. Washington, DC, ASM Press, 1995, pp 905-910
Useful For: Rapid qualitative detection of Epstein-Barr virus DNA in specimens for laboratory
diagnosis of disease due to this virus
Interpretation: Detection of Epstein-Barr virus (EBV) DNA in cerebrospinal fluid (CSF) supports
the clinical diagnosis of central nervous system (CNS) disease due to the virus. EBV DNA is not
detected in CSF from patients without CNS disease caused by this virus.
Reference Values:
Negative
Useful For: Rapid qualitative detection of Epstein-Barr virus DNA in specimens for laboratory
diagnosis of disease due to this virus
Interpretation: Detection of Epstein-Barr virus supports the clinical diagnosis of disease due to the
virus.
Reference Values:
Negative
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acquired immunodeficiency syndrome-related primary central nervous system lymphoma. Ann Neurol
1999;45(2):259-261 3. Niller HH, Wolf H, Minarovits J. Regulation and dysregulation of Epstein-Barr
virus latency: implications for the development of autoimmune disease. Autoimmunity. May
2008:41(4):298-328. 4. Studahl M, Hagberg L, Rekvdar E, Bergstrom T: Herpesvirus DNA detection in
cerebrospinal fluid: difference in clinical presentation between alph-, beta-, and gamma-herpes viruses
Scand J Infect Dis 2000;32(3):237-248 5. Lau AH, Soltys K, Sindhi RK, et al: Chronic high
Epstein-Barr viral load carriage in pediatric small bowel transplant recipients. Pediatr Transplant 2010
Jun;14(4):549-553
Useful For: A prospective and diagnostic marker for the development of posttransplant
lymphoproliferative disorders (PTLD), especially in Epstein-Barr virus (EBV)-seronegative organ
transplant recipients who receive anti-lymphocyte globulin for induction immunosuppression and OKT-3
treatment for early rejection
Interpretation: Increasing copy levels of Epstein-Barr virus (EBV) DNA in serial specimens may
indicate possible posttransplant lymphoproliferative disorders (PTLD). Positive results are quantitated in
copies/mL. Reportable range is 2,000 to 200,000,000 copies/mL. Specimens with results <5,000 copies
EBV DNA/mL include a disclaimer that states: "Results may not be reproducible due to low copy
number." Blood specimens of normal blood donors for EBV infection usually have low or undetectable
levels of viral DNA.
Reference Values:
None detected
Clinical References: 1. Paya CV, Fung JJ, Nalesnik MA, et al: Epstein-Barr virus-induced
posttransplant lymphoproliferative disorders. ASTS/ASTP EBV-PTLD Task Force and the Mayo Clinic
Organized International Consensus Development Meeting. Transplantation 1999;68(10):1517-1525 2.
Kenagy DN, Schlesinger K, Weck JH, et al: Epstein-Barr virus DNA in peripheral blood leukocytes of
patients with posttransplant lymphoproliferative disease. Transplantation 1995;60(6):547-554 3. Green
MJ, Bueno D, Rowe G, et al: Predictive negative value of persistent low Epstein-Barr virus viral load
after intestinal transplantation in children. Transplantation 2000;70(4):593-596 4. Kogan DL, Burroughs
M, Emre S, et al: Prospective longitudinal analysis of quantitative Epstein-Barr virus polymerase chain
reaction in pediatric liver transplant recipients. Transplantation 1999;67(7):1068-1070 5. Green M,
Cacciarelli TV, Mazariegos GV, et al: Serial measurement of Epstein-Barr viral load in peripheral blood
in lymphoproliferative disease. Transplantation 1998;66(12):1641-1644 6. Lau AH, Soltys K, Sindhi RK,
et al: Chronic high Epstein-Barr viral load carriage in pediatric small bowel transplant recipients. Pediatr
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Transplant 2010 Jun;14(4):549-553
Useful For: Determining excision repair cross complementing (ERCC1) polypeptide levels in cells
Interpretation: This test includes only technical performance of the stain (no pathologist
interpretation is performed). If diagnostic consultation by a pathologist is required order 70012 /
Pathology Consultation. The positive and negative controls are verified as showing appropriate
immunoreactivity. If a control tissue is not included on the slide, a scanned image of the relevant quality
control tissue is available upon request. Please contact 1-855-516-8404. Interpretation of this test should
be performed in the context of the patient's clinical history and other diagnostic tests by a qualified
pathologist.
Clinical References: 1. Lee KH, Min HS, Han SW, et al: ERCC1 expression by
immunohistochemistry and EGFR mutations in resected non-small cell lung cancer. Lung Cancer 2008
Jun;60(3):401-407 2. Breen D, Barlesi F: The place of excision repair cross complementation 1
(ERCC1) in surgically treated non-small cell lung cancer. Eur J Cardiothorac Surg 2008
May;33(5):805-811
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smoking), cyanotic heart disease, high-altitude living, renal cysts and tumors, hepatoma, and other
Epo-secreting tumors. When these common causes of secondary erythrocytosis are excluded, a heritable
cause involving hemoglobin or erythrocyte regulatory mechanisms may be present. A less common
cause of secondary polycythemia is the presence of a high-oxygen-affinity hemoglobin. A subset of
hemoglobins with increased oxygen (O2) affinity result in clinically evident erythrocytosis caused by
decreased O2 unloading at the tissue level. The most common symptoms are headache, dizziness,
tinnitus, and memory loss. The affected individuals are plethoric, but not cyanotic. Patients with a
high-oxygen-affinity hemoglobin may present with an increased erythrocyte count, hemoglobin
concentration, and hematocrit, but normal leukocyte and platelet counts. The p50 and
2,3-bisphosphoglycerate (2,3-BPG, also known as 2,3-DPG) values are low. Changes to the amino acid
sequence of the hemoglobin molecule may distort the molecular structure, affecting O2 transport and
the binding of 2,3-BPG. 2,3-BPG is critical to O2 transport of erythrocytes because it regulates the O2
affinity of hemoglobin. A decrease in the 2,3-BPG concentration within erythrocytes results in greater
O2 affinity of hemoglobin and reduction in O2 delivery to tissues. A few cases of erythrocytosis have
been described as being due to a reduction in 2,3-BPG formation. This is most commonly due to
mutations in the converting enzyme, bisphosphoglycerate mutase (BPGM). Mutations in the genes
EPOR, EPAS1(HIF2A), EGLN1(PHD2), and VHL also cause hereditary erythrocytosis and a subset are
associated with subsequent pheochromocytoma and paragangliomas. The prevalence of these mutations
is unknown, but they appear less prevalent than mutations that cause high-oxygen-affinity hemoglobin
variants, and much less prevalent than polycythemia vera. Because there are many causes of
erythrocytosis, an algorithmic and reflexive testing strategy is useful. Initial JAK2 V617F mutation
testing and serum Epo levels are important with p50 results further stratifying JAK2-negative cases.
Useful For: Definitive evaluation of an individual with JAK2-negative erythrocytosis associated with
lifelong sustained increased red blood cell mass, elevated red blood cell count, hemoglobin, or hematocrit
Interpretation: The evaluation includes testing for a hemoglobinopathy and oxygen (O2) affinity of
the hemoglobin molecule. An increase in O2 affinity is demonstrated by a shift to the left in the O2
dissociation curve (decreased p50 result). A hematopathologist expert in these disorders will evaluate the
case, appropriate tests are performed, and an interpretive report is issued.
Reference Values:
Definitive results and an interpretive report will be provided.
Useful For: An aid in distinguishing between primary and secondary polycythemia Differentiating
between appropriate secondary polycythemia (eg, high-altitude living, pulmonary disease, tobacco use)
and inappropriate secondary polycythemia (eg, tumors) Identifying candidates for erythropoietin (EPO)
replacement therapy (eg, chronic renal failure) Evaluating patients undergoing EPO replacement
therapy who demonstrate an inadequate hematopoietic response
Interpretation: In the appropriate clinical setting (eg, confirmed elevation of hemoglobin >18.5
gm/dL, persistent leukocytosis, persistent thrombocytosis, unusual thrombosis, splenomegaly, and
erythromelalgia), polycythemia vera is unlikely when erythropoietin (EPO) levels are elevated and
polycythemia vera is likely when EPO levels are suppressed. EPO levels are also increased in patients
with anemia of bone marrow failure, iron deficiency, or thalassemia. Patients, who have either a poor or
no erythropoietic response to EPO therapy, but high-normal or high EPO levels, may have additional,
unrecognized cause(s) for their anemia. If no contributing factors can be identified after adequate
further study, the possibility that the patient may have developed EPO-antibodies should be considered.
This can be a serious clinical situation that can result in red cell aplasia, and should prompt expeditious
referral to hematologists or immunologists skilled in diagnosing and treating this disorder.
Reference Values:
2.6-18.5 mIU/mL
Clinical References: 1. Tefferi A: Diagnosing polycythemia vera: a paradigm shift. Mayo Clin
Proc 1999;74:159-162 2. Hoagland HC: Myelodysplastic (preleukemia) syndromes: the bone marrow
factory failure problem. Mayo Clin Proc 1995;70:673-677 3. Casadeval N: Pure red cell aplasia and
anti-erythropoietin antibodies in patients treated with epoetin. Nephrol Dial Transplant 2003;18 (Suppl.
8):viii37-viii41 4. Fisher JW: Erythropoietin: physiology and pharmacology update. Exp Biol Med
2003;228:1-14 5. Strippoli GFM, Manno C, Schena FP, Craig JC: Haemoglobin and haematocrit targets
for the anaemia of chronic kidney disease. The Cochrane Library, 2005, Volume 2
Useful For: The definitive evaluation of an individual with JAK2-negative erythrocytosis associated
with lifelong sustained increased RBC mass, elevated RBC count, hemoglobin, or hematocrit
Reference Values:
Only orderable as part of a profile. For more information see HEMP / Hereditary Erythrocytosis
Mutations.
Clinical References:
Age Range
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Newborn
Levels are markedly elevated at birth and fall rapidly during the first week to prepubertal values of <15.
Males <6 m
Levels increase to 10 - 32 between 30 and 60 days, then decline to prepubertal levels of <15 by six
months.
Females <1 y
Levels increase to 5.0 - 50 between 30 and 60 days, then decline to prepubertal levels of <15 during the
first year.
Prepubertal <15
Adult Males 8.0 - 35
Adult Females
Follicular 30 - 100
Luteal 70 - 300
Postmenopausal <15
Age Range
Adult Males 1.7 - 5.4
Adult Females 1.6 - 3.6
Age Range
Adult Males 0.2 - 1.5
Adult Females 0.6 - 7.1
Age Range
Infants (1 - 23m) 60.0 - 252.0
Prepubertal 72.0 - 220.0
Pubertal
Males 16.0 - 100.0
Females 36.0 - 125.0
Adult Males
20 - 49 y 16.5 - 55.9
>49y 19.3 - 76.4
Adult Females
20 49y 24.6 - 122.0
>49y 17.3 - 125.0
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postmenopausal osteoporosis. The 3 most biologically active estrogens in order of potency are estrone
(E1), estradiol (E2), and estriol (E3). Estrogens are produced primarily in the ovary (follicle, corpus
luteum), but small quantities are also formed in the testes and in the adrenal cortex. During pregnancy,
estrogens are mainly formed in the placenta. About 98% of estradiol is bound to transport proteins (sex
hormone-binding globulin: SHBG) and albumin. Estrogen secretion is biphasic during the menstrual
cycle. The determination of estradiol is utilized clinically in the elucidation of fertility disorders in the
hypothalamus-pituitary-gonad axis, gynecomastia, estrogen-producing ovarian and testicular tumors,
and in hyperplasia of the adrenal cortex. Additional clinical indications are the monitoring of fertility
therapy and determining the time of ovulation within the framework of in vitro fertilization (IVF). The
laboratory plays an important role in the process of ovulation induction. The principle involves
administration of gonadotropins to stimulate follicular growth, followed by human chorionic
gonadotropin (hCG) to stimulate ovulation follicular maturation. Clinical, laboratory, and ultrasound
monitoring of the treatment cycle is necessary to identify the dose and length of therapy, determine
when or whether to administer hCG, and obtain an adequate ovulatory response while avoiding
hyperstimulation.
Useful For: Rapid assessment of ovarian status, including follicle development, for assisted
reproduction protocols (eg, in vitro fertilization) Establishing time of ovulation and optimal time for
conception For other clinical indications, order EEST / Estradiol, Serum.
Interpretation: Optimal time for conception is within 48 to 72 hours following the midcycle estradiol
peak. Serial specimens must be drawn over several days to evaluate baseline and peak estradiol levels.
Low baseline levels and a lack of rise, as well as persistent high levels without midcycle rise, are
indicative of anovulatory cycles. For determining the timing of initiation of ovarian stimulation in in vitro
fertilization (IVF) studies, low levels before stimulation are critical, as higher values often are associated
with poor stimulation cycles. Before final human chorionic gonadotropin (hCG) stimulation at mid-IVF
cycle, estradiol concentrations above 2,000 to 3,000 pg/mL are considered by some IVF specialists to be
indicative of an increased likelihood of ovarian hyperstimulation and it may be advisable to consider
withholding further hCG stimulation. Estradiol (E2) concentrations <200 pg/mL following midcycle
stimulation (hCG or follicle-stimulating hormone: FSH) are associated with very low pregnancy success
rates. E2 concentrations change during the menstrual cycle, as follows: -<50 pg/mL before mid-follicular
phase -250 to 500 pg/mL midcycle peak as the follicle matures -Abrupt decrease after ovulation -125
pg/mL peak during the luteal phase Estrogen replacement in reproductive-age women should aim to
mimic natural estrogen levels as closely as possible. E2 levels should be within the reference range for
premenopausal women and luteinizing hormone and FSH should be within the normal range.
Reference Values:
Males: 10-40 pg/mL
Females
Premenopausal: 15-350 pg/mL*
Postmenopausal: <10 pg/mL
*Estradiol concentrations vary widely throughout the menstrual cycle
The limit of quantitation for estradiol measured by immunoassay is 25 pg/mL. Mass spectrometry is the
preferred method for measurement of low serum estradiol concentrations in children, males and
postmenopausal females (EEST / Estradiol, Serum).
Clinical References: 1. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Fifth
edition. Edited by CA Burtis, ER Ashwood, DE Bruns. St. Louis, Elsevier Saunders Company, 2013 2.
Huang JYJ, Rosenwaks Z: Preventative strategies of ovarian hyperstimulation syndrome. J Exp Clin Med
2010;2:53-62 3. Practice Committee of the American Society for Reproductive Medicine. Ovarian
hyperstimulation syndrome. Fertil Steril 2008 Nov;90(5 Suppl):S188-S193
Useful For: All applications that require moderately sensitive measurement of estradiol: -Evaluation
of hypogonadism and oligo-amenorrhea in females -Assessing ovarian status, including follicle
development, for assisted reproduction protocols (eg, in vitro fertilization) -In conjunction with
lutenizing hormone measurements, monitoring of estrogen replacement therapy in hypogonadal
premenopausal women -Evaluation of feminization, including gynecomastia, in males -Diagnosis of
estrogen-producing neoplasms in males, and, to a lesser degree, females -As part of the diagnosis and
work-up of precocious and delayed puberty in females, and, to a lesser degree, males -As part of the
diagnosis and work-up of suspected disorders of sex steroid metabolism, eg, aromatase deficiency and
17 alpha-hydroxylase deficiency -As an adjunct to clinical assessment, imaging studies and bone
mineral density measurement in the fracture risk assessment of postmenopausal women, and, to a lesser
degree, older men -Monitoring low-dose female hormone replacement therapy in post-menopausal
women -Monitoring antiestrogen therapy (eg, aromatase inhibitor therapy)
Interpretation: Estradiol (E2) levels below the premenopausal reference range in young females
indicate hypogonadism. If luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels are
elevated, primary gonadal failure is diagnosed. The main causes are genetic (eg, Turner syndrome,
familial premature ovarian failure), autoimmune (eg, autoimmune ovarian failure, possibly as part of
autoimmune polyglandular endocrine failure syndrome type II), and toxic (eg, related to chemotherapy
or radiation therapy for malignant disease). If LH/FSH levels are low or inappropriately "normal," a
diagnosis of hypogonadotrophic hypogonadism is made. This can have functional causes, such as
starvation, overexercise, severe physical or emotional stress, and heavy drug and/or alcohol use. It also
can be caused by organic disease of the hypothalamus or pituitary. Further work-up is usually
necessary, typically including measurement of pituitary hormones (particularly prolactin), and possibly
imaging. Irregular or absent menstrual periods with normal or high E2 levels (and often high estrone
[E1] levels) are indicative of possible polycystic ovarian syndrome, androgen producing tumors, or
estrogen producing tumors. Further work-up is required and usually includes measurement of total and
bioavailable testosterone, androstenedione, dehydroepiandrosterone (sulfate), sex hormone-binding
globulin, and possibly imaging. E2 levels change during the menstrual cycle, as follows: -Post-menses,
levels may be as low as 15 pg/mL -Levels then rise during the follicular phase to a pre-ovulatory peak,
typically in the 300+ pg/mL range -Levels fall in the luteal phase -Menses typically occur when E2
levels are in the 50 to 100 pg/mL range E2 analysis may be helpful in establishing time of ovulation and
optimal time for conception. Optimal time for conception is within 48 to 72 hours following the
midcycle E2 peak. Serial specimens must be drawn over several days to evaluate baseline and peak total
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estrogen (E1 + E2) levels. Low baseline levels and a lack of rise, as well as persistent high levels
without midcycle rise, are indicative of anovulatory cycles. For determining the timing of initiation of
ovarian stimulation in in vitro fertilization studies, low levels (around 30 pg/mL) before stimulation, are
critical, as higher values often are associated with poor stimulation cycles. Estrogen replacement in
reproductive-age women should aim to mimic natural estrogen levels as closely as possible. E2 levels
should be within the reference range for premenopausal women, LH/FSH should be within the normal
range, and E2 levels should ideally be higher than E1 levels. The current recommendations for
postmenopausal female hormone replacement are to administer therapy in the smallest beneficial doses
for as briefly as possible. Ideally, E2 and E1 levels should be held below, or near, the lower limit of the
premenopausal female reference range. Postmenopausal women and older men in the lowest quartile of
E2 levels are at increased risk of osteoporotic fractures. E2 levels are typically <5 pg/mL in these
patients. Antiestrogen therapy with central or peripheral acting agents that are not pure receptor
antagonists usually aims for complete suppression of E2 production, and in the case of aromatase
inhibitors, complete E1 and E2 suppression. Gynecomastia or other signs of feminization in males may
be due to an absolute or relative (in relation to androgens) surplus of estrogens. Gynecomastia is
common during puberty in boys. Unless E1, E2, or testosterone levels exceed the adult male reference
range, the condition is usually not due to hormonal disease (though it sometimes may still result in
persistent breast tissue, which later needs to be surgically removed). For adults with gynecomastia, the
work-up should include testosterone and adrenal androgen measurements, in addition to E2 and E1
measurements. Causes for increased E1 or E2 levels include: -High androgen levels caused by tumors or
androgen therapy (medical or sport performance enhancing), with secondary elevations in E1 and E2
due to aromatization -Obesity with increased tissue production of E1 -Decreased E1 and E2 clearance in
liver disease -Estrogen producing tumors -Estrogen ingestion Normal male E1 and E2 levels also may
be associated with feminization or gynecomastia, if bioavailable testosterone levels are low due to
primary/secondary testicular failure. This may occur, for example, when patients are receiving
antiandrogen therapy or other drugs with antiandrogenic effects (eg, spironolactone, digitalis
preparations). The gonadotrophin-releasing hormone stimulation test remains the central part of the
work-up for precocious puberty. However, baseline sex steroid and gonadotrophin measurements also
are important. Prepubertal girls have E2 levels <10 pg/mL (most <5 pg/mL). Levels in prepubertal boys
are less than half the levels seen in girls. LH/FSH are very low or undetectable. E1 levels also are low,
but may rise slightly in obese children after onset of adrenarche. E2, which is produced in the gonads,
should remain low in these children. In true precocious puberty, both E2 and LH/FSH levels are
elevated above the prepubertal range. Elevation of E2 or E1 alone suggests pseudo-precocious puberty,
possibly due to a sex steroid-producing tumor. In delayed puberty, estrogens and gonadotrophins are in
the prepubertal range. A rise over time predicts the spontaneous onset of puberty. Persistently low
estrogens and elevated gonadotrophins suggest primary ovarian failure, while low gonadotrophins
suggest hypogonadotrophic hypogonadism. In this latter case, Kallmann syndrome (or related disorders)
or hypothalamic/pituitary tumors should be excluded in well-nourished children. Inherited disorders of
sex steroid metabolism are usually associated with production abnormalities of other steroids, most
notably a lack of cortisol. Aromatase deficiency is not associated with cortisol abnormalities and usually
results in some degree of masculinization in affected females, as well as primary failure of puberty.
Males may show delayed puberty and delayed epiphyseal closure, as well as low bone-density. E2 and
E1 levels are very low or undetectable. Various forms of testicular feminization are due to problems in
androgen signaling pathways and are associated with female (or feminized) phenotypes in genetic
males. E2 and E1 levels are above the male reference range, usually within the female reference range,
and testosterone levels are very high. See Steroid Pathways in Special Instructions.
Reference Values:
Tanner Stages# Mean Age Reference Range
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 786
Stage V 18 years 10-40 pg/mL #Puberty onset (transition
from Tanner stage I to Tanner stage II)
occurs for boys at a median age of 11.5 (+/-
2) years. For boys, there is no proven
relationship between puberty onset and
body weight or ethnic origin. Progression
through Tanner stages is variable. Tanner
stage V (adult) should be reached by age 18.
Females
Useful For: A part of the SEQF/ Sequential Maternal Screening, Part 2, Serum and QUAD / Quad
Screen (Second Trimester) Maternal, Serum in biochemical second trimester or cross-trimester screening
for Down syndrome and trisomy 18 syndrome A marker of fetal demise An element in the prenatal
diagnosis of disorders of fetal steroid metabolism, including Smith-Lemli-Opitz syndrome, X-linked
ichthyosis and contiguous gene syndrome (placental sulfatase deficiency disorders), aromatase deficiency,
primary or secondary fetal adrenal insufficiency, and various forms of congenital adrenal hyperplasia
Assessment of preterm labor risk Epidemiological studies of breast cancer risk in conjunction with
measurement of estrone, estradiol, and various metabolites Assessing estrogen metabolism, estrogen and
estrogen-like medications, and other endogenous or exogenous factors impacting on estrogen metabolism
in the context of other basic scientific and clinical studies
Interpretation: In the context of the quad test, the measured unconjugated E3 (uE3) value forms part
of a complex, multivariate risk calculation formula, using maternal age, gestational stage, and other
demographic information, in addition to the results of the 4 tested markers, for Down syndrome, trisomy
18 syndrome, and neural tube defect risk calculations. A serum uE3 <0.3 multiples of the gestational age
median in women who otherwise screen negative in the quad test, indicates the possibility of fetal demise,
Smith-Lemli-Opitz syndrome, X-linked ichthyosis or contiguous gene syndrome, aromatase deficiency, or
primary or secondary (including maternal corticosteroid therapy) fetal adrenal insufficiency. An elevated
serum or uE3 >3.0 multiples of the gestational age mean, or with an absolute value of >2.1 ng/mL, can be
an indication of pending labor or fetal congenital adrenal hyperplasia. In the context of assessment of a
patient deemed at risk of preterm labor, a single serum or uE3 measurement within the above cutoffs, has
a negative predictive value of labor onset (ie, labor unlikely within the next 4 weeks) of 98% in low-risk
populations and of 96% in high-risk populations. Measurements of serum uE3 performed in the context of
epidemiological or other basic or clinical scientific studies need to be interpreted in the context of those
studies. No overall guidelines can be given.
Reference Values:
Males: <0.07 ng/mL
Females: <0.08 ng/mL
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 788
60871 Estrogen Recptor (ER), Immunostain Without Interpretation
Clinical Information: Estrogen receptor alpha protein expression is limited to normal and
neoplastic tissues related to the reproductive system (breast, cervix, endometrium, uterus, ovary, and
prostate).
Useful For: Qualitative detection of estrogen receptor alpha protein in a diagnostic setting
Interpretation: This test includes only technical performance of the stain (no pathologist
interpretation is performed). If diagnostic consultation by a pathologist is required order 70012 /
Pathology Consultation. The positive and negative controls are verified as showing appropriate
immunoreactivity. If a control tissue is not included on the slide, a scanned image of the relevant quality
control tissue is available upon request. Please contact 1-855-516-8404. Interpretation of this test should
be performed in the context of the patient's clinical history and other diagnostic tests by a qualified
pathologist. Estrogen Receptor IHC, No interp provides qualitative results only. For semiquantitative
assessment of estrogen receptor as a predictive/prognostic marker in the setting of breast cancer, order
89213 / Estrogen/Progesterone Receptor, Semi-Quantitative Immunohistochemistry, Manual and return
Mayo stained no interp ER and PR slides along with H&E OR block/3 unstained slides.
Clinical References: 1. Dabbs DJ, Landreneau RJ, Liu Y, et al: Detection of estrogen receptor by
immunohistochemistry in pulmonary adenocarcinoma. Ann Thorac Surg 2002 February;73(2):403-405
2. Radzikowska E, Langfort R, Giedronowicz D: Estrogen and progesterone receptors in non small cell
lung cancer patients. Ann Thorac Cardiovasc Surg 2002 April;8(2):69-73 3. Leav I, Lau KM, Adams
JY, et al: Comparative studies of the estrogen receptors beta and alpha and the androgen receptor in
normal human prostate glands, dysplasia, and in primary and metastatic carcinoma. Am J Pathol 2001
July;159(1):79-92
Useful For: The test is most frequently used in breast carcinomas when decisions on hormonal
therapy must be made. While the test can be performed on any formalin-fixed, paraffin-embedded
tissue, it is infrequently used for non-breast cancer specimens.
Reference Values:
Negative: <1% reactive cells
Focal positive: 1-10% reactive cells
Positive: >10% reactive cells
Useful For: This test allows the simultaneous high-sensitivity determination of serum estrone and
estradiol levels. It is useful in situations requiring either higher sensitivity estradiol measurement, or
estrone measurement, or both. This includes the following: -As part of the diagnosis and workup of
precocious and delayed puberty in females, and, to a lesser degree, males -As part of the diagnosis and
workup of suspected disorders of sex steroid metabolism, eg, aromatase deficiency and 17
alpha-hydroxylase deficiency -As an adjunct to clinical assessment, imaging studies, and bone mineral
density measurement in the fracture risk assessment of postmenopausal women, and, to a lesser degree,
older men -Monitoring low-dose female hormone replacement therapy in postmenopausal women
-Monitoring antiestrogen therapy (eg, aromatase inhibitor therapy) Useful in all applications that require
moderately sensitive measurement of estradiol including: -Evaluation of hypogonadism and
oligo-amenorrhea in females -Assessing ovarian status, including follicle development, for assisted
reproduction protocols (eg, in vitro fertilization) In conjunction with luteinizing hormone measurements,
monitoring of estrogen replacement therapy in hypogonadal premenopausal women Evaluation of
feminization, including gynecomastia, in males Diagnosis of estrogen-producing neoplasms in males, and,
to a lesser degree, females
Interpretation: Estradiol (E2) levels below the premenopausal reference range in young females
indicate hypogonadism. If luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels are
elevated, primary gonadal failure is diagnosed. The main causes are genetic (eg, Turner syndrome,
familial premature ovarian failure), autoimmune (eg, autoimmune ovarian failure, possibly as part of
autoimmune polyglandular endocrine failure syndrome type II), and toxic (eg, related to chemotherapy or
radiation therapy for malignant disease). If LH/FSH levels are low or inappropriately "normal," a
diagnosis of hypogonadotrophic hypogonadism is made. This can have functional causes, such as
starvation, overexercise, severe physical or emotional stress, and heavy drug and/or alcohol use. It also
can be caused by organic disease of the hypothalamus or pituitary. Further work-up is usually necessary,
typically including measurement of pituitary hormones (particularly prolactin), and possibly imaging.
Irregular or absent menstrual periods with normal or high E2 levels (and often high estrone [E1] levels)
are indicative of possible polycystic ovarian syndrome, androgen producing tumors, or estrogen
producing tumors. Further work-up is required and usually includes measurement of total and bioavailable
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 790
testosterone, androstenedione, dehydroepiandrosterone (sulfate), sex hormone-binding globulin, and
possibly imaging. E2 analysis may be helpful in establishing time of ovulation and optimal time for
conception. Optimal time for conception is within 48 to 72 hours following the midcycle E2 peak. Serial
specimens must be drawn over several days to evaluate baseline and peak total estrogen (E1 + E2) levels.
Low baseline levels and a lack of rise, as well as persistent high levels without midcycle rise are
indicative of anovulatory cycles. For determining the timing of initiation of ovarian stimulation in in vitro
fertilization studies, low levels (around 30 pg/mL) before stimulation are critical, as higher values often
are associated with poor stimulation cycles. Estrogen replacement in reproductive age women should aim
to mimic natural estrogen levels as closely as possible. E2 levels should be within the reference range for
premenopausal women, LH/FSH should be within the normal range, and E2 levels should ideally be
higher than E1 levels. The current recommendations for postmenopausal female hormone replacement are
to administer therapy in the smallest beneficial doses for as briefly as possible. Ideally, E2 and E1 levels
should be held below, or near, the lower limit of the premenopausal female reference range.
Postmenopausal women and older men in the lowest quartile of E2 levels are at increased risk of
osteoporotic fractures. E2 levels are typically <5 pg/mL. Antiestrogen therapy with central or peripheral
acting agents that are not pure receptor antagonists usually aims for complete suppression of E2
production, and in the case of aromatase inhibitors, complete E1 and E2 suppression. Gynecomastia or
other signs of feminization in males may be due to an absolute or relative (in relation to androgens)
surplus of estrogens. Gynecomastia is common during puberty in boys. Unless E1, E2, or testosterone
levels exceed the adult male reference range, the condition is usually not due to hormonal disease (though
it sometimes may still result in persistent breast tissue, which later needs to be surgically removed). For
adults with gynecomastia, the workup should include testosterone and adrenal androgen measurements, in
addition to E2 and E1 measurements. Causes for increased E1 or E2 levels include: -High androgen levels
caused by tumors or androgen therapy (medical or sport performance enhancing), with secondary
elevations in E1 and E2 due to aromatization -Obesity with increased tissue production of E1 -Decreased
E1 and E2 clearance in liver disease -Estrogen producing tumors -Estrogen ingestion Normal male E1 and
E2 levels also may be associated with feminization or gynecomastia, if bioavailable testosterone levels are
low due to primary/secondary testicular failure. This may occur, for example, when patients are receiving
antiandrogen therapy or other drugs with antiandrogenic effects (eg, spironolactone, digitalis
preparations). The gonadotrophin-releasing hormone (GnRH) stimulation test remains the central part of
the workup for precocious puberty. However, baseline sex steroid and gonadotrophin measurements also
are important. Prepubertal girls have E2 levels <10 pg/mL (most <5 pg/mL). Levels in prepubertal boys
are less than half the levels seen in girls. LH/FSH are very low or undetectable. E1 levels also are low, but
may rise slightly, in obese children after onset of adrenarche. E2, which is produced in the gonads, should
remain low in these children. In true precocious puberty, both E2 and LH/FSH levels are elevated above
the prepubertal range. Elevation of E2 or E1 alone suggests pseudo precocious puberty, possibly due to a
sex steroid-producing tumor. In delayed puberty, estrogens and gonadotrophins are in the prepubertal
range. A rise over time predicts the spontaneous onset of puberty. Persistently low estrogens and elevated
gonadotrophins suggest primary ovarian failure, while low gonadotrophins suggest hypogonadotrophic
hypogonadism. In this latter case, Kallman syndrome (or related disorders) or hypothalamic/pituitary
tumors should be excluded in well-nourished children. Inherited disorders of sex steroid metabolism are
usually associated with production abnormalities of other steroids, most notably a lack of cortisol.
Aromatase deficiency is not associated with cortisol abnormalities and usually results in some degree of
masculinization in affected females, as well as primary failure of puberty. Males may show delayed
puberty and delayed epiphyseal closure, as well as low bone-density. E2 and E1 levels are very low or
undetectable. Various forms of testicular feminization are due to problems in androgen signaling
pathways and are associated with female (or feminized) phenotypes in genetic males. E2 and E1 levels are
above the male reference range, usually within the female reference range, and testosterone levels are very
high.
Reference Values:
Tanner Stages# Mean Age Reference Range
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 792
Stage IV 12.3 years 15-85 pg/mL
Clinical References: 1. Elmlinger MW, Kuhnel W, Ranke MB: Reference ranges for serum
concentrations of lutropin (LH), follitropin (FSH), estradiol (E2), prolactin, progesterone, sex
hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), cortisol and ferritin in
neonates, children and young adults. Clin Chem Lab Med 2002;40(11):1151-1160 2. Cummings SR,
Browner WS, Bauer D, et al: Endogenous hormones and the risk of hip and vertebral fractures among
older women. N Engl J Med 1998;339:733-738 3. Lughetti L, Predieri B, Ferrari M, et al: Diagnosis of
central precocious puberty: endocrine assessment. J Pediatr Endocrinol Metab 2000;13 Suppl 1:709-715
4. Ismail AA, Barth JH: Endocrinology of gynaecomastia. Ann Clin Biochem 2001;38:596-607 5.
Kligman I, Rosenwaks Z: Differentiating clinical profiles: predicting good responders, poor responders,
and hyperresponders. Fertil Steril 2001;76:1185-1190 6. Traggiai C, Stanhope R: Delayed puberty. Best
Pract Res Clin Endocrinol Metab 2002;16:139-151
E1 Estrone, Serum
81418 Clinical Information: Estrogens are involved in development and maintenance of the female
phenotype, germ cell maturation, and pregnancy. They also are important for many other,
nongender-specific processes, including growth, nervous system maturation, bone
metabolism/remodeling, and endothelial responsiveness. The 2 major biologically active estrogens in
nonpregnant humans are estrone (E1) and estradiol (E2). A third bioactive estrogen, estriol (E3), is the
main pregnancy estrogen, but plays no significant role in nonpregnant women or men. E2 is produced
primarily in ovaries and testes by aromatization of testosterone. Small amounts are produced in the
adrenal glands and some peripheral tissues, most notably fat. By contrast, most of the circulating E1 is
derived from peripheral aromatization of androstenedione (mainly adrenal). E2 and E1 can be converted
into each other, and both can be inactivated via hydroxylation and conjugation. E2 demonstrates 1.25-5
times the biological potency of E1. E2 circulates at 1.5-4 times the concentration of E1 in
premenopausal, nonpregnant women. E2 levels in men and postmenopausal women are much lower
than in nonpregnant women, while E1 levels differ less, resulting in a reversal of the premenopausal
E2:E1 ratio. E2 levels in premenopausal women fluctuate during the menstrual cycle. They are lowest
during the early follicular phase. E2 levels then rise gradually until 2 to 3 days before ovulation, at
which stage they start to increase much more rapidly and peak just before the ovulation-inducing
luteinizing hormone/follicle stimulating hormone surge at 5 to 10 times the early follicular levels. This
is followed by a modest decline during the ovulatory phase. E2 levels then increase again gradually
until the midpoint of the luteal phase and thereafter decline to trough, early follicular levels.
Measurement of serum E2 forms an integral part of the assessment of reproductive function in females,
including assessment of infertility, oligo-amenorrhea and menopausal status. In addition, it is widely
used for monitoring ovulation induction, as well as during preparation for in vitro fertilization. For these
applications E2 measurements with modestly sensitive assays suffice. However, extra sensitive E2
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 793
assays or simultaneous measurement of E1, or both are needed in a number of other clinical situations.
These include inborn errors of sex steroid metabolism, disorders of puberty, estrogen deficiency in men,
fracture risk assessment in menopausal women, and increasingly, therapeutic drug monitoring, either in
the context of low-dose female hormone replacement therapy or antiestrogen treatment. See Steroid
Pathways in Special Instructions.
Useful For: As part of the diagnosis and work-up of precocious and delayed puberty in females, and, to
a lesser degree, males As part of the diagnosis and work-up of suspected disorders of sex steroid
metabolism, eg, aromatase deficiency and 17 alpha-hydroxylase deficiency As an adjunct to clinical
assessment, imaging studies and bone mineral density measurement in the fracture risk assessment of
postmenopausal women, and, to a lesser degree, older men Monitoring low-dose female hormone
replacement therapy in post-menopausal women Monitoring antiestrogen therapy (eg, aromatase inhibitor
therapy)
Interpretation: Irregular or absent menstrual periods with normal or high E2 levels (and often high E1
levels) are indicative of possible polycystic ovarian syndrome, androgen producing tumors, or estrogen
producing tumors. Further work-up is required and usually includes measurement of total and bioavailable
testosterone, androstenedione, dehydroepiandrosterone (sulfate), sex hormone-binding globulin, and
possibly imaging. Estrogen replacement in reproductive age women should aim to mimic natural estrogen
levels as closely as possible. E2 levels should be within the reference range for premenopausal women,
luteinizing hormone/follicle-stimulating hormone (LH/FSH) should be within the normal range, and E2
levels should ideally be higher than E1 levels. Postmenopausal women and older men in the lowest
quartile of E2 levels are at increased risk of osteoporotic fractures. E2 levels are typically <5 pg/mL in
these patients. The current recommendations for postmenopausal female hormone replacement are to
administer therapy in the smallest beneficial doses for as briefly as possible. Ideally, E2 and E1 levels
should be held below, or near, the lower limit of the premenopausal female reference range. Antiestrogen
therapy with central or peripheral acting agents that are not pure receptor antagonists usually aims for
complete suppression of E2 production, and in the case of aromatase inhibitors, complete E1 and E2
suppression. Gynecomastia or other signs of feminization in males may be due to an absolute or relative
(in relation to androgens) surplus of estrogens. Gynecomastia is common during puberty in boys. Unless
E1, E2, or testosterone levels exceed the adult male reference range, the condition is usually not due to
hormonal disease (though it sometimes may still result in persistent breast tissue, which later needs to be
surgically removed). For adults with gynecomastia, the work-up should include testosterone and adrenal
androgen measurements, in addition to E2 and E1 measurements. Causes for increased E1 or E2 levels
include: -High androgen levels caused by tumors or androgen therapy (medical or sport performance
enhancing), with secondary elevations in E1 and E2 due to aromatization -Obesity with increased tissue
production of E1 -Decreased E1 and E2 clearance in liver disease -Estrogen producing tumors -Estrogen
ingestion Normal male E1 and E2 levels also may be associated with feminization or gynecomastia if
bioavailable testosterone levels are low due to primary/secondary testicular failure. This may occur, for
example, when patients are receiving antiandrogen therapy or other drugs with antiandrogenic effects (eg,
spironolactone, digitalis preparations). The gonadotrophin-releasing hormone stimulation test remains the
central part of the work-up for precocious puberty. However, baseline sex steroid and gonadotrophin
measurements also are important. Prepubertal girls have E2 levels <10 pg/mL (most <5 pg/mL). Levels in
prepubertal boys are less than half the levels seen in girls. LH/FSH are very low or undetectable. E1 levels
also are low, but may rise slightly in obese children after onset of adrenarche. E2, which is produced in
the gonads, should remain low in these children. In true precocious puberty, both E2 and LH/FSH levels
are elevated above the prepubertal range. Elevation of E2 or E1 alone suggests pseudo precocious
puberty, possibly due to a sex steroid-producing tumor. In delayed puberty, estrogens and gonadotrophins
are in the prepubertal range. A rise over time predicts the spontaneous onset of puberty. Persistently low
estrogens and elevated gonadotrophins suggest primary ovarian failure, while low gonadotrophins suggest
hypogonadotrophic hypogonadism. In this latter case, Kallman syndrome (or related disorders) or
hypothalamic/pituitary tumors should be excluded in well-nourished children. Inherited disorders of sex
steroid metabolism are usually associated with production abnormalities of other steroids, most notably a
lack of cortisol. Aromatase deficiency is not associated with cortisol abnormalities and usually results in
some degree of masculinization in affected females, as well as primary failure of puberty. Males may
show delayed puberty and delayed epiphyseal closure, as well as low bone-density. E2 and E1 levels are
very low or undetectable. Various forms of testicular feminization are due to problems in androgen
signaling pathways and are associated with female (or feminized) phenotypes in genetic males. E2 and E1
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 794
levels are above the male reference range, usually within the female reference range, and testosterone
levels are very high. See Steroid Pathways in Special Instructions.
Reference Values:
Tanner Stages# Mean Age Reference Range
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 795
ALC Ethanol, Blood
8264 Clinical Information: Ethanol is the single most important substance of abuse in the United States. It
is the active agent in beer, wine, vodka, whiskey, rum, and other liquors. Ethanol acts on cerebral
functions as a depressant similar to general anesthetics. This depression causes most of the typical
symptoms such as impaired thought, clouded judgment, and changed behavior. As the level of alcohol
increases, the degree of impairment becomes progressively increased. In most jurisdictions in the United
States, the level of prima facie evidence of being under the influence of alcohol for purposes of driving a
motor vehicle is 80 mg/dL.
Useful For: Detection of ethanol (ethyl alcohol) in blood to document prior consumption or
administration of ethanol Quantification of the concentration of ethanol in blood correlates directly with
degree of intoxication
Interpretation: The presence of ethanol in blood at concentrations >30 mg/dL (>0.03% or g/dL) is
generally accepted as a strong indicator of the use of an alcohol-containing beverage. Blood ethanol levels
>50 mg/dL (>0.05%) are frequently associated with a state of increased euphoria. Blood ethanol level >80
mg/dL (>0.08%) exceeds Minnesota's legal limit for driving a motor vehicle. These levels are frequently
associated with loss of manual dexterity and with sedation. A blood alcohol level > or =400 mg/dL (> or
=0.4%) may be lethal as normal respiration may be depressed below the level necessary to maintain life.
The blood ethanol level is also useful in diagnosis of alcoholism. A patient who chronically consumes
ethanol will develop a tolerance to the drug, and requires higher levels than described above to achieve
various states of intoxication. An individual who can function in a relatively normal manner with a blood
ethanol level >150 mg/dL (>0.15%) is highly likely to have developed a tolerance to the drug achieved by
high levels of chronic intake.
Reference Values:
Not detected (Positive results are quantified.)
Limit of detection: 10 mg/dL (0.01 g/dL)
Legal limit of intoxication is 80 mg/dL (0.08 g/dL).
Toxic concentration is dependent upon individual usage history.
Potentially lethal concentration: > or =400 mg/dL (0.4 g/dL)
Clinical References: Porter WF, Moyer TP: Clinical toxicology. In Tietz Textbook of Clinical
Chemistry. Fourth edition. Edited by CA Burtis, ER Ashwood. Philadelphia, WB Saunders Company,
1993, pp 1155-1235
Useful For: Detection of ethanol (ethyl alcohol) in blood to document prior consumption or
administration of ethanol Quantification of the concentration of ethanol in blood correlates directly with
degree of intoxication Chain-of-custody is required whenever the results of testing could be used in a
court of law. Its purpose is to protect the rights of the individual contributing the specimen by
demonstrating that it was under the control of personnel involved with testing the specimen at all times;
this control implies that the opportunity for specimen tampering would be limited.
Interpretation: The presence of ethanol in blood at concentrations greater than 30 mg/dL (>0.03% or
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 796
g/dL) is generally accepted as a strong indicator of the use of an alcohol-containing beverage. Blood
ethanol levels greater than 50 mg/dL (>0.05%) are frequently associated with a state of increased
euphoria. Blood ethanol level greater than 80 mg/dL (>0.08%) exceeds Minnesota's legal limit for driving
a motor vehicle. These levels are frequently associated with loss of manual dexterity and with sedation. A
blood alcohol level greater than or equal to 400 mg/dL (> or =0.4%) may be lethal as normal respiration
may be depressed below the level necessary to maintain life. The blood ethanol level is also useful in
diagnosis of alcoholism. A patient who chronically consumes ethanol will develop a tolerance to the drug,
and requires higher levels than described above to achieve various states of intoxication. An individual
who can function in a relatively normal manner with a blood ethanol level greater than 150 mg/dL
(>0.15%) is highly likely to have developed a tolerance to the drug achieved by high levels of chronic
intake.
Reference Values:
Not detected (Positive results are quantified.)
Limit of detection: 10 mg/dL (0.01 g/dL)
Legal limit of intoxication is 80 mg/dL (0.08 g/dL).
Toxic concentration is dependent upon individual usage history.
Potentially lethal concentration: > or =400 mg/dL (0.4 g/dL)
Clinical References: Porter WF, Moyer TP: Clinical toxicology. In Tietz Textbook of Clinical
Chemistry. Fourth edition. Edited by CA Burtis, ER Ashwood. Philadelphia, WB Saunders Company,
1993, pp 1155-1235
Useful For: Detection of ethanol (ethyl alcohol) in serum to document prior consumption or
administration of ethanol Quantification of the concentration of ethanol in serum correlates with degree
of intoxication.
Interpretation: The presence of ethanol in blood at concentrations >30 mg/dL (>0.03% or 0.03
g/dL) is generally accepted as a strong indicator of the use of an alcohol-containing beverage. Blood
ethanol levels >50 mg/dL (>0.05%) are frequently associated with a state of increased euphoria. Blood
ethanol levels > or =80 mg/dL (0.08%) exceeds Minnesota's legal limit for driving a motor vehicle.
These levels are frequently associated with loss of manual dexterity and with sedation. A blood alcohol
level > or =400 mg/dL (>0.4) may be lethal as normal respiration may be depressed below the level
necessary to maintain life. The blood ethanol level is also useful in diagnosis of alcoholism. A patient
who chronically consumes ethanol will develop a tolerance to the drug and requires higher levels than
described above to achieve various states of intoxication. An individual who can function in a relatively
normal manner with a blood ethanol level >150 mg/dL (>0.15%) is highly likely to have developed a
tolerance to the drug achieved by high levels of chronic intake.
Reference Values:
<10 mg/dL
Legal limit of intoxication: > or =80 mg/dL
Critical value: > or =400 mg/dL
Clinical References: 1. Caplan YH: In Forensic Science Handbook. Vol 2. Edited by R Saferstein.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 797
Prentice Hall, 1982 2. Goodman, Gilman's: The Pharmacological Basis of Therapeutics. 10th edition.
Edited by AG Gilman, JG Hardman, LE LImbird. McGraw-Hill book Company, 2001 3. Porter WF,
Moyer TP: Clinical toxicology. In Tietz Textbook of Clinical Chemistry. Fourth edition. Edited by CA
Burtis, ER Ashwood. Philadelphia, WB Saunders Company, 1993, pp 1155-1235 4. Levine B:
Principles of Forensic Toxicology. AACC Press, 1999
Reference Values:
Therapeutic: 40-100 mcg/mL
Critical value: >150 mcg/mL
Clinical References: 1. Patsalos PN, Berry DJ, Bourgeois BF, et al: Antiepileptic drugs-best practice
guidelines for therapeutic drug monitoring: a position paper by the subcommission on therapeutic drug
monitoring, ILAE Commission on Therapeutic Strategies. Epilepsia 2008;49(7):1239-1276 2. Moyer TP:
Therapeutic drug monitoring. In Tietz Textbook of Clinical Chemistry. Third edition. Edited by CA
Burtis, ER Ashwood. WB Saunders Company, Philadelphia, 1999, pp 862-905
Please note: The therapeutic range for ethotoin is not well established.
Useful For: Monitoring abstinence in clinical and justice system settings using ethyl blucuronide and
ethyl sulfate as direct biomarkers or metabolites of ethanol This chain-of-custody test is intended to be
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 798
used in a setting where the test results can be used definitively to make a diagnosis.
Interpretation: A positive interpretation will be given if either the ethyl glucuronide result is greater
than or equal to 250 ng/mL and/or the ethyl sulfate is greater than or equal to 100 ng/mL. A "high"
positive (ie, >1,000 ng/mL) may indicate: -Heavy drinking on the same day or previously (ie, previous
day or 2). -Light drinking the same day A "low" positive (ie, 500-1,000 ng/mL) may indicate: -Previous
heavy drinking (ie, previous 1-3 days). -Recent light drinking (ie, past 24 hours). -Recent intense
"extraneous" exposure (ie, within 24 hours or less). A "very low" positive (ie, 100-500 ng/mL) may
indicate: -Previous heavy drinking (ie, 1-3 days) -Previous light drinking (ie, 12-36 hours). -Recent
"extraneous" exposure.
Reference Values:
Negative
Cutoff concentrations:
Ethyl Glucuronide: 500 ng/mL
Clinical References: 1. Reisfield GM, Goldberger BA, Crews BO, et al: Ethyl glucuronide, ethyl
sulfate, and ethanol in urine after sustained exposure to an ethanol-based hand sanitizer. J Anal Toxicol
2011;35:85-91 2. The role of biomarkers in the treatment of alcohol use disorders. 2012 Revision
Substance Abuse and Mental Health Services Administration. Spring 2012;11(2):1-7
Useful For: Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are direct biomarkers or metabolites of
ethanol. EtG and EtS can be detected up to 5 days in urine using a cutoff of 500 ng/mL.(1) These
biomarkers are often used in monitoring abstinence in clinical and justice system settings.
Interpretation: A positive interpretation will be given if either the ethyl glucuronide result is greater
than or equal to 250 ng/mL and/or the ethyl sulfate is greater than or equal to 100 ng/mL. A "high"
positive (ie, >1,000 ng/mL) may indicate: -Heavy drinking on the same day or previously (ie, previous
day or 2). -Light drinking the same day A "low" positive (ie, 500-1,000 ng/mL) may indicate: -Previous
heavy drinking (ie, previous 1-3 days). -Recent light drinking (ie, past 24 hours). -Recent intense
"extraneous" exposure (ie, within 24 hours or less). A "very low" positive (ie, 100-500 ng/mL) may
indicate: -Previous heavy drinking (ie, 1-3 days) -Previous light drinking (ie, 12-36 hours). -Recent
"extraneous" exposure.(2)
Reference Values:
Negative
Clinical References: 1. Reisfield GM, Goldberger BA, Crews BO, et al: Ethyl glucuronide, ethyl
sulfate, and ethanol in urine after sustained exposure to an ethanol-based hand sanitizer. J Anal Toxicol
2011;35:85-91 2. The role of biomarkers in the treatment of alcohol use disorders. 2012 Revision
Substance Abuse and Mental Health Services Administration. Spring 2012;11(2):1-7
Reference Values:
Negative
Screening cutoff concentration:
Ethyl Glucuronide: 500 ng/mL
Reference Values:
Negative
Screening cutoff concentration:
Ethyl Glucuronide: 500 ng/mL
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 800
chromatography/electrospray ionization/tandem mass spectrometry according to forensic guidelines. J Am
Soc Mass Spectrom 2004;15(2):188-193
Reference Values:
Toxic concentration: > or =20 mg/dL
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 801
the concentration of IgE antibodies expressed as a class score or kU/L.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: Providing diagnostic information and guiding treatment primarily for patients with
mammary analogue secretory carcinoma, secretory carcinoma of the breast, and infantile fibrosarcoma
Interpretation: A positive result is detected when the percent of cells with an abnormality exceeds the
normal cutoff for the probe set. A positive result suggests rearrangement of the ETV6 locus, which can be
useful for diagnosis. A negative result suggests no rearrangement of the ETV6 gene region at 12p13.2.
Reference Values:
An interpretive report will be provided.
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 803
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 804
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Reference Values:
3-8 ng/mL
Target steady-state trough concentrations vary depending on the type of transplant, concomitant
immunosuppression, clinical/institutional protocols, and time post-transplant. Results should be
interpreted in conjunction with this clinical information and any physical signs/symptoms of
rejection/toxicity.
Clinical References: 1. Eisen HJ, Tuzcu EM, Dorent R, et al: Everolimus for the prevention of
allograft rejection and vasculopathy in cardiac-transplant recipients. N Engl J Med 2003;349(9):847-858
2. Kovarik JM, Beyer D, Schmouder RL: Everolimus drug interactions: application of a classification
system for clinical decision making. Biopharm Drug Dispos 2006;27(9):421-426 3. Rothenburger M,
Zuckermann A, Bara C, et al: Recommendations for the use of everolimus (Certican) in heart
transplantation: results from the second German-Austrian Certican Consensus Conference. J Heart Lung
Transplant 2007;26(4):305-311 4. Sanchez-Fructuoso AI: Everolimus: an update on the mechanism of
action, pharmacokinetics and recent clinical trials. Expert Opin Drug Metab Toxicol 2008;4(6):807-819
Useful For: Supporting the diagnosis of Ewing sarcoma (EWS)/primitive neuroectodermal tumor
(PNET), myxoid chondrosarcoma, desmoplastic small, round cell tumor, clear cell sarcoma, and myxoid
liposarcoma when used in conjunction with an anatomic pathology consultation An aid in the diagnosis of
EWS when reverse transcriptase-PCR results are equivocal or do not support the clinical picture
Interpretation: A neoplastic clone is detected when the percent of cells with an abnormality exceeds
the normal cutoff for the EWSR1 FISH probe set. A positive result is consistent with a diagnosis of
Ewing sarcoma (EWS)/primitive neuroectodermal tumors (PNET). A negative result suggests that a
EWSR1 rearrangement is not present but does not exclude the diagnosis of EWS/PNET.
Reference Values:
An interpretive report will be provided.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 806
2 lesions are essentially identical. Less common are the t(21;22)(p22;q12) or EWSR1-ERG transcript,
present in <5% of ES/PNET tumors, and the t(7:22)(p22;q12) or EWSR1-FEV transcript, present in <1%
of these tumors. These fusion transcripts can be detected by reverse-transcriptase PCR (RT-PCR), by
FISH, chromogenic in situ hybridization, or by classical cytogenetic analyses. The RT-PCR and FISH
procedures are the most sensitive methods to detect these fusion transcripts.(3)
Useful For: Supporting a diagnosis of Ewing sarcoma and primitive neuroectodermal tumors
Interpretation: A positive EWSR1-FLI1 or EWSR1-ERG result is consistent with a diagnosis of
Ewing sarcoma and primitive neuroectodermal tumor (ES/PNET). Sarcomas other than ES/PNET, and
carcinomas, melanomas, and lymphomas are negative for the fusion products. A negative result does
not rule out a diagnosis of ES/PNET.
Reference Values:
An interpretative report will be provided.
Clinical References: 1. Delattree O, Zucman J, Melot T, et al: The Ewing family of tumors-A
subgroup of small-round-cell tumors defined by specific chimeric transcripts. N Engl J Med
1994;331:218-222 2. Barr FG, Chatten J, D'Cruz CM, et al: Molecular assays for chromosomal
translocations in the diagnosis of pediatric soft tissue sarcomas. JAMA 1995;273:553-557 3. Ladanyi
M, Bridge JA: Contribution of molecular genetic data to the classification of sarcomas. Hum Pathol
2000;31:532-538 4. Jin L, Majerus J, Oliveira A, by et al: Detection of fusion gene transcripts in
fresh-frozen and formalin-fixed paraffin-embedded tissue sections of soft tissue sarcomas after laser
capture microdissection and RT-PCR. Diagn Mol Pathol 2003;12:224-230 5. Zucman J, Melot T,
Desmaze C, et al: Combinatorial generation of variable fusion proteins in the Ewing family of tumours.
EMBO J 1993;12:4481-4487
Reference Values:
Negative: <20.0 U
Weak Positive: 20.0-30.0 U
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 807
Positive: >30.0 U
Useful For: The assessment of in vivo lipid peroxidation and considered to be an index of systemic
oxidative stress over time
Interpretation: Elevated urinary F2-isoprostanes reflect widespread oxidative stress and systemic
burden of lipid peroxidation end products. Quantitation of F2-isoprostanes in urine is highly dependent
upon the methodology utilized; however, mass spectrometry methods (gas chromatography-mass
spectrometry or liquid chromatography-tandem mass spectrometry) assays yield superior sensitivity and
analytical specificity compared with immunoassays. F2-isoprostanes demonstrate superior clinical
sensitivity compared to other oxidative stress biomarkers but lack clinical specificity for any particular
disease. Pharmacological treatment with antioxidant supplementation, hypoglycemic agents in diabetes,
smoking cessation, and weight reduction have all been shown to decrease production of F2-isoprostanes.
Reference Values:
> or =18 years: < or =1.0 ng/mg creatinine
<18 years: not established
Clinical References: 1. Strobel NA, Fassett RG, Marsh SA, Coombes JS: Oxidative stress
biomarkers as predictors of cardiovascular disease. Int J Cardiol 2011;147:191-201 2. Davies SS, Roberts,
LJ: F2-isoprostanes as an indicator and risk factor for coronary heart disease. Free Radic Biol Med 2011
Mar 1;50(5):559-566 3. Kontush A, de Faria EC, Chantepie S, Chapman MJ: A normotriglyceridemic,
low HDL-cholesterol phenotype is characterized by an elevated oxidative stress and HDL particles with
attenuated antioxidative activity. Atherosclerosis 2005;182:277-285 4. Vassale C, Botto N, Andreassi
MG, et al: Evidence for enhanced 8-isoprostane plasma levels, as an index of oxidative stress in vivo, for
patients with coronary artery disease. Coron Artery Dis 2003 May;14(3):213-218
Useful For: Confirmation of a diagnosis of classic or variant Fabry disease in affected males with
reduced alpha-Gal A enzyme activity Carrier or diagnostic testing for asymptomatic or symptomatic
females, respectively
Interpretation: All detected alterations will be evaluated according to the American College of
Medical Genetics and Genomics (AMCG) recommendations.(2) Variants will be classified based on
known, predicted, or possible pathogenicity and reported with interpretive comments detailing their
potential or known significance.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Hwu WL, Chien YH, Lee NC, et al: Newborn screening for Fabry disease
in Taiwan reveals a high incidence of the later-onset GLA mutation c.936+919G>A). Hum Mutat
2009:30(10):1397-1405 2. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for
standards of interpretation and reporting of sequence variations: revisions 2007. Genet Med
2008;10(4):294-300 3. Germain DP: Fabry disease. Orphanet J Rare Dis. 2010 Nov 22;5:30 4 Wang
RY, Lelis A, Mirocha J, Wilcox WR: Heterozygous Fabry women are not just carriers, but have a
significant burden of disease and impaired quality of life. Genet Med 2007 Jan;9(1):34-35
Useful For: An aid in the identification of acquired digital fibrokeratomas, angiofibromas, and oral
fibroma, and a proportion of cells in histiocytomas
Interpretation: This test includes only technical performance of the stain (no pathologist
interpretation is performed). If diagnostic consultation by a pathologist is required order 70012 /
Pathology Consultation. The positive and negative controls are verified as showing appropriate
immunoreactivity. If a control tissue is not included on the slide, a scanned image of the relevant quality
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control tissue is available upon request. Please contact 1-855-516-8404. Interpretation of this test should
be performed in the context of the patient's clinical history and other diagnostic tests by a qualified
pathologist.
Clinical References: 1. Goldblum JR, Tuthill RJ: CD34 and Factor-XIIIa immunoreactivity in
dermatofibrosarcoma protuberans and dermatofibroma. The American Journal of Dermatopathology
1997;19(2):147-153 2. Gray MH, Smoller BR, McNutt S, Hsu A: Immunohistochemical demonstration of
Factor XIIIa expression in neurofibromas. A practical means of differentiating these tumors from
neurotized melanocyte nevi and schwannomas. Arch Dermatol 1990;126(4):472-476 3. Zoltan N, Vilmos
T: Factor XIIIa and the classic histiocytic markers in malignant fibrous histiocytoma: A comparative
immunotochemical study. Human Pathology 1988;19(7):822-829
Useful For: Detection and titering of coagulation inhibitor to the specific factor requested, primarily
factor IX in patients with hemophilia B
Interpretation: Normally, there is no inhibitor (ie, negative result). If the screening assays indicate the
presence of an inhibitor, it will be quantitated and reported in Bethesda (or equivalent) units.
Reference Values:
FACTOR IX ACTIVITY ASSAY
Adults: 65-140%
Normal, full-term newborn infants or healthy premature infants may have decreased levels (> or
=20%), which may not reach adult levels for > or =180 days postnatal.*
*See Pediatric Hemostasis References in Coagulation Studies in Special Instructions.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 810
BETHESDA TITER
0 Units
Clinical References: 1. Feinstein DI, Rapaport, SI: Acquired inhibitors of blood coagulation. In
Hematology: Basic Principles and Practice. Edited by R Hoffman, EJ Benz Jr, SJ Shattil, et al. New
York, Livingstone Press, 1991, pp 1380-1394 2. Chitlur M, Warrier I, Rajpurkar M, et al: Inhibitors in
factor IX deficiency a report of the ISTH-SSC international FIX inhibitor registry (1997-2006).
Haemophilia 2009;15(5):1027-1031
Useful For: Factor V Leiden mutation testing should be reserved for patients with clinically
suspected thrombophilia and: 1) APC-resistance proven or suspected by a low or borderline
APC-resistance ratio, or 2) a family history of factor V Leiden.
Interpretation: The interpretive report will include specimen information, assay information,
background information, and conclusions based on the test results (normal, heterozygous FV R506Q,
homozygous FV R506Q).
Reference Values:
Negative
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 811
Edited by CS Kitchens, BM Alving, CM Kessler. Saunders 2012
Useful For: Detecting the presence and titer of a specific factor inhibitor directed against coagulation
factor VIII
Interpretation: Normally, there is no inhibitor, (ie, negative result). If the screening assays indicate the
presence of an inhibitor, it will be quantitated and reported in Bethesda (or equivalent) units.
Reference Values:
FACTOR VIII ACTIVITY ASSAY
Adults: 55-200%
Normal, full-term newborn infants or healthy premature infants usually have normal or elevated factor
VIII.*
*See Pediatric Hemostasis References in Coagulation Studies in Special Instructions.
BETHESDA TITER
0 Units
Clinical References: 1. Kasper CK: Treatment of factor VIII inhibitors. Prog Hemost Thromb
1989;9:57-86 2. Peerschke EI, Castellone DD, Ledford-Kraemer M, et al: Laboratory assessment of FVIII
inhibitor titer. Am J Clin Pathol 2009;131(4):552-558 3. Pruthi RK, Nichols WL: Autoimmune factor
VIII inhibitors. Curr Opin Hematol 1999;6(5):314-322
FX13M Factor XIII, Qualitative, with Reflex to Factor XIII 1:1 Mix
57302 Reference Values:
Factor XIII, Qualitative: No Lysis
Factor XIII, 1:1 Mix: Not Applicable
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 812
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 813
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Carrier screening for familial dysautonomia in individuals of Ashkenazi Jewish ancestry
Prenatal diagnosis of familial dysautonomia in at-risk pregnancies Confirmation of a clinical diagnosis of
familial dysautonomia in individuals of Ashkenazi Jewish ancestry
Clinical References: 1. Gross SJ, Pletcher BA, Monaghan KG: Carrier screening in individuals of
Ashkenazi Jewish descent. Genet Med 2008 Jan;10(1):54-56 2. Gold-von Simson G, Axelrod FB:
Familial dysautonomia: update and recent advances. Curr Probl Pediatr Adolesc Health Care 2006
Jul;36(6):218-237
Useful For: Aiding in the diagnosis of familial hypercholesterolemia (FH) Distinguishing the
diagnosis of FH from other causes of hyperlipidemia, such as familial defective apoB-100 and familial
combined hyperlipidemia
Clinical References: 1. Hobbs H, Brown MS, Goldstein JL: Molecular genetics of the LDL
receptor gene in familial hypercholesterolemia. Hum Mutat 1992;1:445-446 2. Goldstein JL, Hobbs H,
Brown MS: Familial hypercholesterolemia. In The Metabolic Basis of Inherited Disease. Edited by CR
Scriver, AL Beaudet, D Valle, WS Sly. New York, McGraw-Hill Book Company, 2006, pp 2863-2913
3. van Aalst-Cohen ES, Jansen AC, Tanck MW, et al: Diagnosing familial hypercholesterolaemia: the
relevance of genetic testing. Eur Heart J 2006;27:2440-2446
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 815
(EGF) precursor homology regions in the 5' region of the gene (type II and III variants, respectively).
Although most FH-causing variants are small (eg, point variants), approximately 10% to15% of variants
in the LDLR gene are large rearrangements such as exonic deletions and duplications, which are not
amenable to sequencing (eg, LDLRS / Familial Hypercholesterolemia, LDLR Full Gene Sequencing)
but can be detected by this MLPA assay.
Useful For: Aiding in the diagnosis of familial hypercholesterolemia (FH) in individuals with elevated
untreated low-density lipoprotein (LDL) cholesterol Distinguishing the diagnosis of FH from other causes
of hyperlipidemia, such as familial defective ApoB-100 and familial combined hyperlipidemia
Comprehensive LDL receptor genetic analysis for suspect FH individuals who test negative for an LDLR
point variant by sequencing (LDLRS / Familial Hypercholesterolemia, LDLR Full Gene Sequencing)
Clinical References: 1. Hobbs H, Brown MS, Goldstein JL: Molecular genetics of the LDL receptor
gene in familial hypercholesterolemia. Hum Mutat 1992:1:445-466 2. Goldstein JL, Hobbs H, Brown MS:
Familial hypercholesterolemia. In The Metabolic Basis of Inherited Disease. Edited by CR Scriver, AL
Beaudet, D Valle, et al New York, McGraw-Hill Book Company, 2006 pp 2863-2913 3. Van Aalst-Cohen
ES, Jansen AC, Tanck MW, et al: Diagnosing familial hypercholesterolemia: the relevance of genetic
testing. Eur Heart J 2006;27:2240-2246 4. Soutar AK, Naoumova RP: Mechanisms of disease: genetic
causes of familial hypercholesterolemia. Nat Clin Pract Cardiovasc Med 2007;4(4):214-225 5. Schouten
JP, McElgunn CJ, Waaijer R, et al: Relative quantification of 40 nucleic acid sequences by multiplex
ligation-dependent probe amplification. Nucleic Acids Res, 2002;30(12):e57
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chromosome 2p. The vast majority of FDB cases are caused by a single APOB variant at residue 3500,
resulting in a glutamine substitution for the arginine residue (R3500Q). This common FDB variant occurs
at an estimated frequency of 1 in 500 individuals of European descent. A less frequently occurring variant
at that same codon, which results in a tryptophan substitution (R3500W), is more prevalent in individuals
of Chinese and Malay descent, and has been identified in the Scottish population as well. The R3500W
variant is estimated to occur in approximately 2% of ADH cases. Residue 3500 interacts with other
apolipoprotein B-100 residues to induce conformational changes necessary for apolipoprotein B-100
binding to the LDL receptor. Thus, variants at residue 3500 lead to a reduced binding affinity of LDL for
its receptor. Identification of 1 or more variants in individuals suspected of having ADH helps to
determine appropriate treatment of this disease. Treatment is aimed at lowering plasma LDL levels and
increasing LDL receptor activity. FH heterozygotes and FDB homozygotes and heterozygotes are often
treated with 3-hydroxy-3-methylglutaryl CoA reductase inhibitors (ie, statins), either in monotherapy or in
combination with other drugs such as nicotinic acid and inhibitors of intestinal cholesterol absorption.
Such drugs are generally not effective in FH homozygotes, and treatment in these individuals may consist
of LDL apheresis, portacaval anastomosis, and liver transplantation. Screening of at-risk family members
allows for effective primary prevention by instituting statin therapy and dietary modifications at an early
stage. This test provides a reflex approach to diagnosing the above disorders. The tests can also be
separately ordered: -LDLRS / Familial Hypercholesterolemia, LDLR Full Gene Sequencing -LDLM /
Familial Hypercholesterolemia, LDLR Large Deletion/Duplication, Molecular Analysis See
Familial/Autosomal Dominant Hypercholesterolemia Diagnostic Algorithm in Special Instructions.
Clinical References: 1. Hobbs HH, Brown MS, Goldstein JL: Molecular genetics of the LDL
receptor gene in familial hypercholesterolemia. Hum Mutat 1992;1:445-466 2. Goldstein JL, Hobbs
HH, Brown MS: Familial hypercholesterolemia. In The Metabolic Basis of Inherited Disease. Edited by
CR Scriver, AL Beaudet, D Valle, WS Sly. New York, McGraw-Hill Book Company, 2006 pp
2863-2913 3. Whitfield AJ, Barrett PH, van Bockxmeer FM, Burnett JR: Lipid disorders and mutations
in the APOB gene. Clin Chem 2004;50:1725-1732 4. Innerarity TL, Mahley RW, Weisgraber KH, et al:
Familial defective apolipoprotein B100: a mutation of apolipoprotein B that causes
hypercholesterolemia. J Lipid Res 1990;31:1337-1349
Useful For: Diagnostic or predictive testing for specific conditions when 1 or more mutations have
been identified in a family member Carrier screening for individuals at risk for having a mutation that was
previously identified in a family member
Interpretation: All detected alterations are evaluated according to American College of Medical
Genetics (ACMG) recommendations.(1) Variants are classified based on known, predicted, or possible
pathogenicity and reported with interpretive comments detailing their potential or known significance.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for
standards for interpretation and reporting of sequence variations: Revisions 2007. Genet Med
2008;10(4):294-300
Useful For: Carrier screening for Fanconi anemia in individuals of Ashkenazi Jewish ancestry Prenatal
diagnosis of Fanconi anemia in at-risk pregnancies Confirmation of suspected clinical diagnosis of
Fanconi anemia in individuals of Ashkenazi Jewish ancestry
Clinical References: 1. Gross SJ, Pletcher BA, Monaghan KG: Carrier screening in individuals of
Ashkenazi Jewish descent. Genet Med 2008 Jan;10(1):54-6 2. Kutler DI, Auerbach AD: Fanconi anemia
in Ashkenazi Jews. Fam Cancer 2004;3(3-4):241-248
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 818
Consultation. The positive and negative controls are verified as showing appropriate immunoreactivity. If
a control tissue is not included on the slide, a scanned image of the relevant quality control tissue is
available upon request. Please contact 1-855-516-8404. Interpretation of this test should be performed in
the context of the patient's clinical history and other diagnostic tests by a qualified pathologist.
Clinical References: 1. Fan G, Kotylo P, Neiman R, Braziel RM: Comparison of fascin expression
in anaplastic large cell lymphoma and Hodgkin disease. Am J Clin Pathol 2003;119:199-204 2. Kempf
W, Levi E, Kamarashev J, et al: Fascin expression in CD30-positive cutaneous lymphoproliferative
disorders. J Cutan Pathol 2002;29:295-300 3. Pinkus GS, Pinkus JL, Langhoff E, et al: Fascin, a
sensitive new marker for reed-sternberg cells of Hodgkins disease. Evidence for a dendritic or B
cell derivation? Am J Pathol 1997;150(2):543-562
Useful For: Diagnosing fat malabsorption due to pancreatic or intestinal disorders Monitoring
effectiveness of enzyme supplementation in certain malabsorption disorders
Interpretation: Excretion of >7 grams fat/24 hours, when on a diet of 100 to 150 g of fat, is
suggestive of a malabsorption defect. Abnormal results from a random specimen should be confirmed
by submission of a timed collection. Test values for timed fecal fat collections will be reported in terms
of g/24 hours; the duration of the collection may be 24, 48, 72, or 96 hours. Test values for random fecal
fat collections will be reported in terms of percent fat.
Reference Values:
TIMED COLLECTION
> or =18 years: 2-7 g fat/24 hours
Reference values have not been established for patients who are <18 years of age.
RANDOM COLLECTION
All ages: 0-19% fat
Clinical References: 1. Henderson AR, Rinker AD: Gastric, pancreatic, and intestinal function. In
Tietz Textbook of Clinical Chemistry. Third edition. Edited by CA Burtis, ER Ashwood. Philadelphia,
WB Saunders Company, 1999, pp 1293-1295 2. Modern Nutrition in Health and Disease.10th edition.
Edited by ME Shils, M Shike, AC Ross, et al. Baltimore, MD, Lippincott Williams and Wilkins, 2006,
pp 1143-1151,1227-1234
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 819
probe assay is to offer screening for several defects of FAO and organic acid metabolism under
controlled laboratory conditions using fibroblast cultures.
Useful For: In vitro confirmation of biochemical diagnoses of the following fatty acid oxidation
disorders: -Short-chain acyl-CoA dehydrogenase (SCAD) deficiency -Medium-chain acyl-CoA
dehydrogenase (MCAD) deficiency -Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD)
deficiency -Trifunctional protein deficiency -Very long-chain acyl-CoA dehydrogenase (VLCAD)
deficiency -Carnitine palmitoyl transferase deficiency type II (CPT-II) -Carnitine-acylcarnitine
translocase (CACT) deficiency In addition, the following organic acid disorders can be confirmed by this
assay: -2-Methylbutyryl-CoA dehydrogenase (SBCAD) deficiency -Isobutyryl-CoA dehydrogenase (IBD)
deficiency Work is in progress to evaluate the applicability of this assay to the remaining disorders of
fatty acid transport and mitochondrial oxidation.
Interpretation: Abnormal results will include a description of the abnormal profile, in comparison to
normal and abnormal corun controls. In addition, the concentration of those acylcarnitine species that
abnormally accumulated in the cell medium are provided and compared to the continuously updated
reference range based on analysis of normal controls. Interpretations of abnormal acylcarnitine profiles
also include information about the results' significance, a correlation to available clinical information,
possible differential diagnoses, recommendations for additional biochemical testing and confirmatory
studies if indicated, name and phone number of contacts who may provide these studies at the Mayo
Clinic or elsewhere, and a phone number to reach one of the laboratory directors in case the referring
physician has additional questions.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Roe CR, Ding J: Chapter 101: Mitochondrial Fatty Acid Oxidation
Disorders. In The Metabolic Basis of Inherited Disease. Eighth edition. Edited by D Valle. AL Beaudet, B
Vogelstein. New York, McGraw-Hill Book Company. Accessed 04/22/2014. Available at:
www.ommbid.com 2. Ensenauer R, Vockley J, Willard JM, et al: A common mutation is associated with
a mild, potentially asymptomatic phenotype in patients with isovaleric acidemia diagnosed by newborn
screening. Am J Hum Genet 2004;75(6):1136-1142 3. Rinaldo P, Matern D, Bennet MJ: Fatty acid
oxidation disorders. Ann Rev Physiol 2002;64:477-502 4. Shen JJ, Matern D, Millington DS, et al:
Acylcarnitines in fibroblasts of patients with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency
and other fatty acid oxidation disorders. J Inherit Metab Dis 2000;23:27-44 5. Matern D, Huey JC,
Gregersen N, et al: In vitro diagnosis of short-chain acyl-CoA dehydrogenase (SCAD) deficiency. J
Inherit Metab Dis 2001;24(Suppl.1):66
Useful For: This plasma test is a comprehensive profile that provides information regarding
mitochondrial and peroxisomal fatty acid metabolism, and the patient's nutritional status Monitoring
patients undergoing diet therapy for mitochondrial or peroxisomal disorders (possibly inducing essential
fatty acid deficiency in response to restricted fat intake) Monitoring treatment of essential fatty acid
deficiency Monitoring the response to provocative tests (fasting tests, loading tests)
Interpretation: An increased triene:tetraene ratio is consistent with essential fatty acid deficiency.
Fatty acid oxidation disorders are recognized on the basis of disease-specific patterns that are correlated
to the results of other investigations in plasma (carnitine, acylcarnitines) and urine (organic acids,
acylglycines). Increased concentrations of very long-chain fatty acids (VLCFA) C24:0 and C26:0 are
seen in peroxisomal disorders, X-linked adrenoleukodystrophy, adrenomyeloneuropathy, and Zellweger
syndrome (cerebrohepatorenal syndrome). Increased concentrations of phytanic acid (along with normal
pristanic acid concentrations) are seen in the Refsum disease (phytanase deficiency). Phytanic acid
concentration also may be increased in other peroxisomal disorders and, when combined with the
VLCFA, pristanoic acid, and pipecolic acid, allows differential diagnosis of peroxisomal disorders.
Reference Values:
Octanoic Acid, C8:0
<1 year: 7-63 nmol/mL
1-17 years: 9-41 nmol/mL
> or =18 years: 8-47 nmol/mL
EPA, C20:5w3
<1 year: 2-60 nmol/mL
1-17 years: 8-90 nmol/mL
> or =18 years: 14-100 nmol/mL
DHA, C22:6w3
<1 year: 10-220 nmol/mL
1-17 years: 30-160 nmol/mL
> or =18 years: 30-250 nmol/mL
DPA, C22:5w6
<1 year: 3-70 nmol/mL
1-17 years: 10-50 nmol/mL
> or =18 years: 10-70 nmol/mL
DPA, C22:5w3
<1 year: 6-110 nmol/mL
1-17 years: 30-270 nmol/mL
> or =18 years: 20-210 nmol/mL
DTA, C22:4w6
<1 year: 2-50 nmol/mL
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 823
1-17 years: 10-40 nmol/mL
> or =18 years: 10-80 nmol/mL
Triene/Tetraene Ratio
< or =31 days: 0.017-0.083
32 days-17 years: 0.013-0.050
> or =18 years: 0.010-0.038
Total w6
<1 year: 0.9-4.4 mmol/L
1-17 years: 1.6-4.7 mmol/L
> or =18 years: 3.0-5.4 mmol/L
Clinical References: 1. Stellaard F, ten Brink HJ, Kok RM et al: Stable isotope dilution analysis
of very long chain fatty acids in plasma, urine, and amniotic fluid by electron capture negative ion mass
fragmentography. Clin Chim Acta 1990;192:133-144 2. ten Brink HJ, Stellaard F, van den Heuvel et al:
Pristanic acid and phytanic acid in plasma from patients with peroxisomal disorders: stable isotope
dilution analysis with electron capture negative ion mass fragmentography. J Lipid Res 1992;33:41-47
3. Rinaldo P, Matern D, Bennett MJ: Fatty acid oxidation disorders. Ann Rev Physiol 2002;64:477-502
4. Jeppesen PB, Chistensen MS, Hoy CE, Mortensen PB: Essential fatty acid deficiency in patients with
severe fat malabsorption. Am J Clin Nutr 1997;65:837-843
Useful For: This serum test is a comprehensive profile that provides information regarding
mitochondrial and peroxisomal fatty acid metabolism, and the patient's nutritional status Monitoring
patients undergoing diet therapy for mitochondrial or peroxisomal disorders (possibly inducing essential
fatty acid deficiency in response to restricted fat intake) Monitoring treatment of essential fatty acid
deficiency Monitoring the response to provocative tests (fasting tests, loading tests)
Interpretation: An increased triene:tetraene ratio is consistent with essential fatty acid deficiency.
Fatty acid oxidation disorders are recognized on the basis of disease-specific patterns that are correlated to
the results of other investigations in plasma (carnitine, acylcarnitines) and urine (organic acids,
acylglycines). Increased concentrations of serum very long-chain fatty acids (VLCFA) C24:0 and C26:0
are seen in peroxisomal disorders, X-linked adrenoleukodystrophy, adrenomyeloneuropathy, and
Zellweger syndrome (cerebrohepatorenal syndrome). Increased concentrations of serum phytanic acid
(along with normal pristanic acid concentrations) are seen in the Refsum disease (phytanase deficiency).
Serum phytanic acid concentration also may be increased in other peroxisomal disorders and, when
combined with the VLCFA, pristanoic acid and pipecolic acid allow differential diagnosis of peroxisomal
disorders.
Reference Values:
Octanoic Acid, C8:0
<1 year: 7-63 nmol/mL
1-17 years: 9-41 nmol/mL
> or =18 years: 8-47 nmol/mL
EPA, C20:5w3
<1 year: 2-60 nmol/mL
1-17 years: 8-90 nmol/mL
> or =18 years: 14-100 nmol/mL
DHA, C22:6w3
<1 year: 10-220 nmol/mL
1-17 years: 30-160 nmol/mL
> or =18 years: 30-250 nmol/mL
DPA, C22:5w6
<1 year: 3-70 nmol/mL
1-17 years: 10-50 nmol/mL
> or =18 years: 10-70 nmol/mL
DPA, C22:5w3
<1 year: 6-110 nmol/mL
1-17 years: 30-270 nmol/mL
> or =18 years: 20-210 nmol/mL
DTA, C22:4w6
<1 year: 2-50 nmol/mL
1-17 years: 10-40 nmol/mL
> or =18 years: 10-80 nmol/mL
Triene/Tetraene Ratio
< or =31 days: 0.017-0.083
32 days-17 years: 0.013-0.050
> or =18 years: 0.010-0.038
Total w3
<1 year: 0.0-0.4 mmol/L
1-17 years: 0.1-0.5 mmol/L
> or =18 years: 0.2-0.5 mmol/L
Total w6
<1 year: 0.9-4.4 mmol/L
1-17 years: 1.6-4.7 mmol/L
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 829
> or =18 years: 3.0-5.4 mmol/L
Clinical References: 1. Rinaldo P, Matern D, Bennett MJ: Fatty acid oxidation disorders. Ann Rev
Physiol 2002;64:477-502 2. Jeppesen PB, Chistensen MS, Hoy CE, Mortensen PB: Essential fatty acid
deficiency in patients with severe fat malabsorption. Am J Clin Nutr 1997;65:837-843 3. McCowen KC,
Bistrian BR: Essential fatty acids and their derivatives. Curr Opin Gastroenterol 2005 Mar;21(2):207-215
Useful For: Evaluating the nutritional intake and intestinal absorption of essential fatty acids
Identifying deficiency of essential and other nutritionally beneficial fatty acids Monitoring treatment of
patients with essential fatty acid deficiencies who are receiving linoleic acid (C18:2w6) and
alpha-linolenic acid (C18:3w3)
Interpretation: Concentrations below the stated reference ranges are consistent with fatty acid
deficiencies. An increased triene:tetraene ratio is consistent with essential fatty acid deficiency
Reference Values:
Lauric Acid, C12:0
<1 year: 6-190 nmol/mL
1-17 years: 5-80 nmol/mL
> or =18 years: 6-90 nmol/mL
EPA, C20:5w3
<1 year: 2-60 nmol/mL
1-17 years: 8-90 nmol/mL
> or =18 years: 14-100 nmol/mL
Homo-Gamma-Linolenic C20:3w6
<1 year: 30-170 nmol/mL
1-17 years: 60-220 nmol/mL
> or =18 years: 50-250 nmol/mL
DHA, C22:6w3
<1 year: 10-220 nmol/mL
1-17 years: 30-160 nmol/mL
> or =18 years: 30-250 nmol/mL
DPA, C22:5w6
<1 year: 3-70 nmol/mL
1-17 years: 10-50 nmol/mL
> or =18 years: 10-70 nmol/mL
DPA, C22:5w3
<1 year: 6-110 nmol/mL
1-17 years: 30-270 nmol/mL
> or =18 years: 20-210 nmol/mL
DTA, C22:4w6
<1 year: 2-50 nmol/mL
1-17 years: 10-40 nmol/mL
> or =18 years: 10-80 nmol/mL
Triene/Tetraene Ratio
< or =31 days: 0.017-0.083
32 days-17 years: 0.013-0.050
> or =18 years: 0.010-0.038
Total w3
<1 year: 0.0-0.4 mmol/L
1-17 years: 0.1-0.5 mmol/L
> or =18 years: 0.2-0.5 mmol/L
Total w6
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 832
<1 year: 0.9-4.4 mmol/L
1-17 years: 1.6-4.7 mmol/L
> or =18 years: 3.0-5.4 mmol/L
Clinical References: 1. Stellaard F, ten Brink HJ, Kok RM, et al: Stable isotope dilution analysis
of very long chain fatty acids in plasma, urine, and amniotic fluid by electron capture negative ion mass
fragmentography. Clin Chim Acta 1990;192:133-144 2. Jeppesen PB, Chistensen MS, Hoy CE,
Mortensen PB: Essential fatty acid deficiency in patients with severe fat malabsorption. Am J Clin Nutr
1997;65:837-843
Useful For: Evaluating the nutritional intake and intestinal absorption of essential fatty acids
Identifying deficiency of essential and other nutritionally beneficial fatty acids Monitoring treatment of
patients with essential fatty acid deficiencies who are receiving linoleic acid (C18:2w6) and
alpha-linolenic acid (C18:3w3)
Interpretation: Concentrations below the stated reference ranges are consistent with fatty acid
deficiencies. An increased triene:tetraene ratio is consistent with essential fatty acid deficiency.
Reference Values:
Lauric Acid, C12:0
<1 year: 6-190 nmol/mL
1-17 years: 5-80 nmol/mL
> or =18 years: 6-90 nmol/mL
EPA, C20:5w3
<1 year: 2-60 nmol/mL
1-17 years: 8-90 nmol/mL
> or =18 years: 14-100 nmol/mL
Homo-Gamma-Linolenic C20:3w6
<1 year: 30-170 nmol/mL
1-17 years: 60-220 nmol/mL
> or =18 years: 50-250 nmol/mL
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 834
Arachidic Acid, C20:0
<1 year: 30-120 nmol/mL
1-17 years: 30-90 nmol/mL
> or =18 years: 50-90 nmol/mL
DHA, C22:6w3
<1 year: 10-220 nmol/mL
1-17 years: 30-160 nmol/mL
> or =18 years: 30-250 nmol/mL
DPA, C22:5w6
<1 year: 3-70 nmol/mL
1-17 years: 10-50 nmol/mL
> or =18 years: 10-70 nmol/mL
DPA, C22:5w3
<1 year: 6-110 nmol/mL
1-17 years: 30-270 nmol/mL
> or =18 years: 20-210 nmol/mL
DTA, C22:4w6
<1 year: 2-50 nmol/mL
1-17 years: 10-40 nmol/mL
> or =18 years: 10-80 nmol/mL
Triene/Tetraene Ratio
< or =31 days: 0.017-0.083
32 days-17 years: 0.013-0.050
> or =18 years: 0.010-0.038
Total w3
<1 year: 0.0-0.4 mmol/L
1-17 years: 0.1-0.5 mmol/L
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 835
> or =18 years: 0.2-0.5 mmol/L
Total w6
<1 year: 0.9-4.4 mmol/L
1-17 years: 1.6-4.7 mmol/L
> or =18 years: 3.0-5.4 mmol/L
Clinical References: 1. Jeppesen PB, Chistensen MS, Hoy CE, Mortensen PB: Essential fatty acid
deficiency in patients with severe fat malabsorption. Am J Clin Nutr 1997;65:837-843 2. McCowen KC,
Bistrian BR: Essential fatty acids and their derivatives. Curr Opin Gastroenterol 2005 Mar;21(2):207-215
Useful For: Biochemical diagnosis of inborn errors of mitochondrial fatty acid oxidation, including
deficiencies of medium-chain acyl-Co-A dehydrogenase, long-chain 3-hydroxyacyl-Co-A dehydrogenase,
very long-chain acyl-Co-A dehydrogenase, and glutaricacidemia type 2
Interpretation: Fatty acid oxidation disorders are recognized on the basis of disease-specific
metabolite patterns that are correlated to the results of other investigations in plasma (carnitine,
acylcarnitines) and urine (organic acids, acylglycines).
Reference Values:
Octanoic Acid, C8:0
<1 year: 7-63 nmol/mL
1-17 years: 9-41 nmol/mL
> or =18 years: 8-47 nmol/mL
Useful For: Evaluating patients with possible peroxisomal disorders, including peroxisomal biogenesis
disorders, X-linked adrenoleukodystrophy, and Refsum disease An aid in the assessment of peroxisomal
function
Interpretation: Reports include concentrations of C22:0, C24:0, C26:0 species, phytanic acid and
pristanic acid, and calculated C24:0/C22:0, C26:0/C22:0, and phytanic acid:pristanic acid ratios. When no
significant abnormalities are detected, a simple descriptive interpretation is provided. A profile of elevated
phytanic acid, low-normal pristanic acid, and normal very long-chain fatty acids is suggestive of Refsum
disease (phytanic acid oxidase deficiency); however, phytanic acid concentration may also be increased in
disorders of peroxisomal biogenesis and should be considered in the differential diagnosis of peroxisomal
disorders. If results are suggestive of hemizygosity for X-linked adrenoleukodystrophy, we also include
the calculated value of a discriminating function used to more accurately segregate hemizygous
individuals from normal controls. Positive test results could be due to a genetic or nongenetic condition.
Additional confirmatory testing would be required to differentiate between these causes.
Reference Values:
C22:0
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 838
< or =96.3 nmol/mL
C24:0
< or =91.4 nmol/mL
C26:0
< or =1.30 nmol/mL
C24:0/C22:0 RATIO
< or =1.39
C26:0/C22:0 RATIO
< or =0.023
PRISTANIC ACID
0-4 months: < or =0.60 nmol/mL
5-8 months: < or =0.84 nmol/mL
9-12 months: < or =0.77 nmol/mL
13-23 months: < or =1.47 nmol/mL
> or =24 months: < or =2.98 nmol/mL
PHYTANIC ACID
0-4 months: < or =5.28 nmol/mL
5-8 months: < or =5.70 nmol/mL
9-12 months: < or =4.40 nmol/mL
13-23 months: < or =8.62 nmol/mL
> or =24 months: < or =9.88 nmol/mL
Clinical References: 1. Moser AB, Kreiter N, Bezman L, et al: Plasma very long chain fatty acid
assay in 3,000 peroxisome disease patients and 29,000 controls. Ann Neurol 1999;45:100-110 2.
Wanders RJA: Inborn Errors of Peroxisome Biogenesis and Function. In Pediatric Endocrinology and
Inborn Errors of Metabolism. Edited by K Sarafoglou, GF Hoffmann, KS Roth, New York,
McGraw-Hill Medical Division, 2009, pp 323-337
Useful For: Evaluating patients with possible peroxisomal disorders, single-enzyme defects of
peroxisomal metabolism such as X-linked adrenoleukodystrophy or peroxisomal biogenesis disorders
(Zellweger syndrome spectrum) An aid in the assessment of peroxisomal function
Interpretation: Reports include concentrations of C22:0, C24:0, C26:0 species, phytanic acid and
pristanic acid, and calculated C24:0/C22:0, C26:0/C22:0, and phytanic acid:pristanic acid ratios. When no
significant abnormalities are detected, a simple descriptive interpretation is provided. A profile of elevated
phytanic acid, low-normal pristanic acid, and normal very long-chain fatty acids is suggestive of Refsum
disease (phytanic acid oxidase deficiency); however, serum phytanic acid concentration may also be
increased in disorders of peroxisomal biogenesis and should be considered in the differential diagnosis of
peroxisomal disorders. If results are suggestive of hemizygosity for X-linked adrenoleukodystrophy, we
also include the calculated value of a discriminating function used to more accurately segregate
hemizygous individuals from normal controls. Positive test results could be due to a genetic or nongenetic
condition. Additional confirmatory testing would be required to differentiate between these causes.
Reference Values:
C22:0
< or =96.3 nmol/mL
C24:0
< or =91.4 nmol/mL
C26:0
< or =1.30 nmol/mL
C24:0/C22:0 RATIO
< or =1.39
C26:0/C22:0 RATIO
< or =0.023
PRISTANIC ACID
0-4 months: < or =0.60 nmol/mL
5-8 months: < or =0.84 nmol/mL
9-12 months: < or =0.77 nmol/mL
13-23 months: < or =1.47 nmol/mL
> or =24 months: < or =2.98 nmol/mL
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 840
PHYTANIC ACID
0-4 months: < or =5.28 nmol/mL
5-8 months: < or =5.70 nmol/mL
9-12 months: < or =4.40 nmol/mL
13-23 months: < or =8.62 nmol/mL
> or =24 months: < or =9.88 nmol/mL
Clinical References: 1. Moser AB, Kreiter N, Bezman L, et al: Plasma very long chain fatty acid
assay in 3,000 peroxisome disease patients and 29,000 controls. Ann Neurol 1999;45:100-110 2.
Wanders RJA: Inborn Errors of Peroxisome Biogenesis and Function. In Pediatric Endocrinology and
Inborn Errors of Metabolism. Edited by K Sarafoglou, GF Hoffmann, KS Roth, New York,
McGraw-Hill Medical Division, 2009, pp 323-337
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 841
Useful For: An aid in the diagnosis of FBN1-associated Marfan syndrome, autosomal dominant
ectopia lentis, isolated ascending aortic aneurysm and dissection, isolated skeletal features of Marfan
syndrome, MASS phenotype (mitral valve prolapse, aortic diameter increased, stretch marks, skeletal
features of MFS), Shprintzen-Goldberg syndrome, and autosomal dominant Weill-Marchesani syndrome
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Baudhuin LM, Kotzer KE, Lagerstedt SA: Increased frequency of FBN1
truncating and splicing variants in Marfan syndrome patients with aortic events. Genet Med 2015
Mar;17(3):177-187, doi:10.1038/gim.2014.91 2. Baudhuin LM, Kotzer KE, Lagerstedt SA: Decreased
frequency of FBN1 missense variants in Ghent criteria-positive Marfan syndrome and characterization of
novel FBN1 variants. J Hum Genet 2015 May;60(5):241-252, doi: 10.1038/jhg.2015.10 3. Faivre L,
Collod-Beroud G, Loeys BL, et al: Effect of mutation type and location on clinical outcome of 1,013
probands with Marfan syndrome or related phenotypes and FBN1 mutations: an international study. Am J
Hum Genet 2007;81(3):454-466 4. Loeys BL, Dietz HC, Braverman AC, et al: The revised Ghent
nosology for the Marfan syndrome. J Med Genet 2010;47:476-485 5. Boileau C, Jondeau G, Mizuguchi
T, Matsumoto N: Molecular genetics of Marfan syndrome. Curr Opin Cardiol 2005 May;20(3):194-200 6.
Faivre L, Gorlin RJ, Wirtz MK, et al: In frame fibrillin-1 gene deletion in autosomal dominant
Weill-Marchesani syndrome. J Med Genet 2003 Jan;40(1):34-36
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and /or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 842
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. New York,
WB Saunders Company, 2007, Part VI, pp 961-971
Antibodies to Salmonella flagellar (H) and somatic (O) antigens typically peak 3 5 weeks after
infection. A positive results in this assay is equivalent to a titer of >=1:160 by tube agglutination
(Widal). Results should not be considered as diagnostic unless confirmed by culture.
Interpretive Criteria:
<0.80 Antibody not detected
0.80 1.09 Equivocal
> or = 1.10 Antibody detected
Acute brucellosis is characterized by the appearanceof Brucella-specific IgM within the first week of
infection, followed by the appearance of Brucella-specific IgG after the second week. Levels of both
IgM and IgG decline slowly over several months in conjunction with recovery. Persistence of high IgG
levels with declining or absent IgM suggests chronic infection or relapse.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 843
Useful For: Suggesting presence of pathogens such as Salmonella, Shigella, and amebiasis
Interpretation: When fecal leukocytes are found they are reported in a semiquantitative manner: "few"
indicates < or = 2/oil immersion microscopic field (OIF); "moderate" indicates 3/OIF to 9/OIF; "many"
indicates > or = 10/OIF. The greater the number of leukocytes, the greater the likelihood that an invasive
pathogen is present. The finding of many fecal leukocytes is a good indicator of the presence of an
invasive microbiological pathogen such as Salmonella or Shigella. Few or no leukocytes and many
erythrocytes suggests amebiasis. Fecal leukocytes are rarely seen in diarrheas caused by other parasites or
viruses.
Reference Values:
Interpretive report
Clinical References: Pickering LK, DuPont HL, Olarte J, et al: Fecal leukocytes in enteric
infections. Am J Clin Pathol 1977;68:562-565
Reference Values:
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 844
Negative
This test has not been validated in a pediatric population, results should be interpreted in the context of
the patient's presentation.
Clinical References: 1. Levin B, Lieberman DA, McFarland B, et al: Screening and Surveillance
for the Early Detection of Colorectal Cancer and Adenomatous Polyps, 2008: A Joint Guideline from
the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the
American College of Radiology. CA Cancer J Clin 2008;58:130 2. Whitlock EP, Lin JS, Liles E, et al:
Screening for colorectal cancer: a targeted, updated systematic review for the U.S. Preventive Services
Task Force. Ann Intern Med 2008;149:638 3. Hol L, Wilschut JA, van Ballegooijen M, et al: Screening
for colorectal cancer: random comparison of guaiac and immunochemical faecal occult blood testing at
different cut-off levels. Br J Cancer 2009;100:1103 4. Levi Z, Rozen P, Hazazi R, et al: A quantitative
immunochemical fecal occult blood test for colorectal neoplasia. Ann Intern Med 2007;146:244 5.
Tannous B, Lee-Lewandrowski E, Sharples C, et al: Comparison of conventional guaiac to four
immunochemical methods for fecal occult blood testing: implications for clinical practice in hospital
and outpatient settings. Clin Chem Acta 2009;400:120-122
Reference Values:
30.0-60.0 mcg/mL
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testing often depend upon the age of the patient, history of allergen exposure, season of the year, and
clinical manifestations. In individuals predisposed to develop allergic disease(s), the sequence of
sensitization and clinical manifestations proceed as follows: eczema and respiratory disease (rhinitis and
bronchospasm) in infants and children less than 5 years due to food sensitivity (milk, egg, soy, and
wheat proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
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disposition of a specimen to document who collected it, who handled it, and who performed the analysis.
When a specimen is submitted in this manner, analysis will be performed in such a way that it will
withstand regular court scrutiny.
Useful For: Monitoring fentanyl therapy Chain of custody is required whenever the results of testing
could be used in a court of law. Its purpose is to protect the rights of the individual contributing the
specimen by demonstrating that it was under the control of personnel involved with testing the
specimen at all times; this control implies that the opportunity for specimen tampering would be limited.
Interpretation: Both fentanyl and norfentanyl are reported. Tolerant individuals may require
many-fold increases in dose to achieve the same level of analgesia, which can greatly complicate
interpretation of therapeutic drug monitoring (TDMA) results and establishment of a therapeutic
window. Concentration at which toxicity occurs varies and should be interpreted in light of clinical
situation.
Reference Values:
Not applicable
Clinical References: 1. Gutstein HB, Akil H: Chapter 21: Opioid analgesics. In Goodman and
Gilmans The Pharmacological Basis of Therapeutics. Vol. 11. Edited by JG LL Hardman, AG Gilman
AG, New York, McGraw-Hill Book Company, Inc, 2006 2. Kerrigan S, Goldberger BA: Opioids. In
Principles of Forensic Toxicology, Edited by B Levine. Second edition. Washington DC AACC Press,
2003, pp 187-205 3. Package insert: DURAGESIC (fentanyl transdermal system. Pharmaceutica
Products, L.P., 2006 4. Baselt RC: Disposition of Toxic Drugs and Chemicals in Man. Eighth edition.
Foster City, CA. Biochemical Publications. 2008 pp 616-619
Reference Values:
Negative
Screening cutoff concentration:
Fentanyl: 2 ng/mL
Clinical References: 1. Gutstein HB, Akil H: Chapter 21: Opioid analgesics. In Goodman and
Gilman's: The Pharmacological Basis of Therapeutics. Vol 11. Edited by LL Hardman, AG Gilman.
New York, McGraw-Hill Book Company Inc. 2006 2. Kerrigan S, Goldberger BA: Opioids. In
Principles of Forensic Toxicology. Second edition. Edited by ZB Levine. Washington DC, AACC
Press, 2003, pp 187-205
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immunoassay also has a false-negative rate to the antibodys ability to cross-react with different
drugs in the class being screened for.
Reference Values:
Negative
Screening cutoff concentration:
Fentanyl: 2 ng/mL
Clinical References: 1. Gutstein HB, Akil H: Chapter 21: Opioid analgesics. In Goodman and
Gilman's: The Pharmacological Basis of Therapeutics. Vol 11. Edited by LL Brunton, JS Lazo, KL
Parker. New York, McGraw-Hill Book Company Inc. 2006 2. Kerrigan S, Goldberger BA: Opioids. In
Principles of Forensic Toxicology. Second edition. Edited by ZB Levine. Washington DC, AACC Press,
2003, pp 187-205
Useful For: Detection and confirmation of illicit drug use involving fentanyl Chain of custody is
required whenever the results of testing could be used in a court of law. Its purpose is to protect the rights
of the individual contributing the specimen by demonstrating that it was under the control of personnel
involved with testing the specimen at all times; this control implies that the opportunity for specimen
tampering would be limited.
Interpretation: The presence of fentanyl >0.20 ng/mL or norfentanyl >1.0 ng/mL is a strong indicator
that the patient has used fentanyl.
Reference Values:
Negative
Cutoff concentrations:
Immunoassay screen
<2 ng/mL
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Fentanyl by LC-MS/MS
0.2 ng/mL
Norfentanyl by LC-MS/MS
1.0 ng/mL
Clinical References: 1. Gutstein HB, Akil H: Chapter 21: Opioid analgesics. In Goodman and
Gilman's: The Pharmacological Basis of Therapeutics. Vol. 11. Edited by JG LL Hardman, AG Gilman.
New York, McGraw-Hill Book Company Inc. 2006 2. Kerrigan S, Goldberger BA: Opioids. In
Principles of Forensic Toxicology. Second Edition. Edited by ZB Levine. Washington DC, AACC
Press, 2003, pp 187-205 3. Package insert: DURAGESIC (fentanyl transdermal system). Janssen
Pharmaceutica Products. Titusville, NJ. LP, 2006 4. Baselt RC: Disposition of Toxic Drugs and
Chemicals in Man. Eighth edition. Foster City, CA. Biomedical Publications, 2008, pp 616-619
Useful For: Detection and confirmation of illicit drug use involving fentanyl
Interpretation: The presence of fentanyl >0.20 ng/mL or norfentanyl >1.0 ng/mL is a strong
indicator that the patient has used fentanyl.
Reference Values:
Negative
Clinical References: 1. Gutstein HB, Akil H: Chapter 21: Opioid analgesics. In Goodman and
Gilman's: The Pharmacological Basis of Therapeutics. Vol. 11. Edited by JG LL Hardman, AG Gilman.
New York, McGraw-Hill Book Company Inc. 2006 2. Kerrigan S, Goldberger BA: Opioids. In
Principles of Forensic Toxicology. Second Edition. Edited by ZB Levine. Washington DC, AACC
Press, 2003, pp 187-205 3. Package insert: DURAGESIC (fentanyl transdermal system). Janssen
Pharmaceutica Products. Titusville, NJ. LP, 2006 4. Baselt RC: Disposition of Toxic Drugs and
Chemicals in Man. Eighth edition. Foster City, CA. Biomedical Publications, 2008, pp 616-619
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 849
the opioid mu-receptor. These mu-binding sites are discretely distributed in the human brain, spinal
cord, and other tissues.(1,3) Fentanyl is approximately 80% to 85% protein bound.(1) Fentanyl plasma
protein binding capacity decreases with increasing ionization of the drug. Alterations in pH may affect
its distribution between plasma and the central nervous system. The average volume of distribution for
fentanyl is 6 L/kg (range 3-8).(3,4) In humans, the drug appears to be metabolized primarily by
oxidative N-dealkylation to norfentanyl and other inactive metabolites that do not contribute materially
to the observed activity of the drug. Within 72 hours of intravenous (IV) administration, approximately
75% of the dose is excreted in urine, mostly as metabolites with <10% representing unchanged
drug.(3,4) The mean elimination half-life is:(1-3) -IV: 2 to 4 hours -Iontophoretic transdermal system
(Ionsys), terminal half-life: 16 hours -Transdermal patch: 17 hours (range 103-22 hours, half-life is
influenced by absorption rate) -Transmucosal: - Lozenge: 7 hours - Buccal tablet - 100 to 200 mcg: 3 to
4 hours - 400 to 800 mcg: 11 to 12 hours In clinical settings, fentanyl exerts its principal pharmacologic
effects on the central nervous system. In additions to analgesia, alterations in mood, euphoria,
dysphoria, and drowsiness commonly occur.(1,3) Because the biological effects of fentanyl are similar
to those of heroin and other opioids, fentanyl has become a popular drug of abuse.
Reference Values:
Not applicable
Clinical References: 1. Gutstein HB, Akil H: Chapter 21: Opioid analgesics. In Goodman and
Gilmans The Pharmacological Basis of Therapeutics. Vol 11. Edited by JG LL Hardman, AG Gilman,
New York, McGraw-Hill Book Company, Inc, 2006 2. Kerrigan S, Goldberger BA: Opioids. In Principles
of Forensic Toxicology. Edited by B Levine. Second edition. Washington DC AACC Press, 2003, pp
187-205 3. Package insert: DURAGESIC (fentanyl transdermal system. Pharmaceutical Products, LP,
2006 4. Baselt RC: Disposition of Toxic Drugs and Chemicals in Man. Eighth edition. Foster City, CA.
Biochemical Publications. 2008 pp 616-619
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
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Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Aiding in the diagnosis of iron deficiency and iron overload conditions Differentiating
iron deficiency anemia and anemia of chronic disease
Interpretation: Hypoferritinemia is associated with increased risk for developing iron deficiency
where iron deficiency is sufficient to reduce erythropoiesis causing hemoglobin concentrations to fall.
Latent iron deficiency occurs when serum ferritin is low without low hemoglobin. Hyperferritinemia is
associated with iron overload conditions including hereditary hemochromatosis where concentrations
may exceed 1,000 mcg/L. Non-iron overload hyperferritinemia may be caused by common liver
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 851
disorders, neoplasms, acute or chronic inflammation, and hereditary hyperferritinemia-cataract
syndrome. For more information about hereditary hemochromatosis testing, see Hereditary
Hemochromatosis Algorithm in Special Instructions.
Reference Values:
Males: 24-336 mcg/L
Females: 11-307 mcg/L
Clinical References: 1. Henry's Clinical Diagnosis and Management by Laboratory Methods. 21st
edition. Edited by RA McPherson, MR Pincus.Philadelphia. Elsevier Saunders, 2007, pp 506 2. Tietz
Textbook of Clinical Chemistry and Molecular Diagnostics. Edited by CA Burtis, ER Ashwood, DE
Bruns. St. Louis, MO, Elsevier Saunders, 2012, pp 985-1030
Interpretation: All detected alterations are evaluated according to American College of Medical
Genetics recommendations.(1) Variants are classified based on known, predicted, or possible
pathogenicity and reported with interpretive comments detailing their potential or known significance.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for
standards of interpretation and reporting of sequence variations: revisions 2007. Genet Med
2008;10(4):294-300 2. Lecha M, Puy H, Deybach JC: Erythropoietic protoporphyria. Orphanet J Rare Dis
2009;4:19 3. Schneider-Yin X, Gouya L, Meier-Weinand A, et al: New insights into the pathogenesis of
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 852
erythropoietic protoporphyria and their impact on patient care. Eur J Pediatr 2000;159:719-725 4.
Rufenacht UB, Gouya L, Schneider-Yin X, et al: Systematic analysis of molecular defects in the
ferrochelatase gene from patients with erythropoietic protoporphyria. Am J Hum Genet
1998;62:1341-1352 5. Whatley SD, Mason NG, Holme SA, et al: Molecular epidemiology of
erythropoietic protoporphyria in the U.K.. Br J Dermatol 2010;162:642-646
Useful For: Determining the volume of fetal-to-maternal hemorrhage for the purposes of
recommending an increased dose of the Rh immune globulin
Interpretation: Greater than 15 mL of fetal red blood cells (RBC) (30 mL of fetal whole blood) is
consistent with significant fetomaternal hemorrhage (FMH). A recommended dose of Rh immune
globulin (RhIG) will be reported for all specimens. One 300 mcg dose of RhIG protects against a FMH
of 30 mL of D-positive fetal whole blood or 15 mL of D-positive fetal RBCs. Recommended standard
of practice is to administer RhIG within 72 hours of the fetomaternal bleed for optimal protective
effects. The effectiveness of RhIG decreases beyond 72 hours post exposure but may still be clinically
warranted. This assay has been validated out to 5 days post collection.
Reference Values:
< or =1.5 mL of fetal RBCs in normal adults
Useful For: Determining the volume of fetal-to-maternal hemorrhage for the purposes of
recommending an increased dose of the Rh immune globulin
Interpretation: Greater than 15 mL of fetal red blood cells (RBC) (30 mL of fetal whole blood) is
consistent with significant fetomaternal hemorrhage (FMH). A recommended dose of Rh immune
globulin (RhIG) will be reported for all specimens. One 300 mcg dose of RhIG protects against a FMH of
30 mL of D-positive fetal whole blood or 15 mL of D-positive fetal RBCs. Recommended standard of
practice is to administer RhIG within 72 hours of the fetomaternal bleed for optimal protective effects.
The effectiveness of RhIG decreases beyond 72 hours post-exposure but may still be clinically warranted.
This assay has been validated out to 5 days post collection.
Reference Values:
< or =1.5 mL of fetal RBCs in normal adults
Useful For: Providing prognostic information and guiding treatment primarily for patients with
squamous cell carcinoma of the lung, breast, esophagus, thymus, and other locations
Interpretation: FGFR1 will be clinically interpreted as positive or negative. The FGFR1 locus is
reported as amplified when the FGFR1:D8Z2 ratio is >2.0 or an average of 6 or more copies of the
FGFR1 locus are observed per tumor nucleus. A tumor with an FGFR1:D8Z2 ratio < or =2.0 and having
an average of <6 copies of FGFR1 per tumor nucleus is considered negative for amplification of the
FGFR1 locus.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Schultheis AM, Bos M, Schmitz K, et al: Fibroblast growth factor receptor 1
(FGFR1) amplification is a potential therapeutic target in small-cell lung cancer. Mod Pathol 2014
Feb;27(2):214-212 2. Heist RS, Mino-Kenudson M, Sequist LV, et al: FGFR1 amplification in squamous
cell carcinoma of the lung. J Thorac Oncol 2012 Dec;7(12):1775-1780 3. Weis J, Sos ML, Seidel D, et al:
Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in
squamous cell lung cancer. Sci Transl Med 2010 Dec 15;2(62):62ra93 4. Craddock KJ, Ludkovski O,
Sykes J, et al: Prognostic value of fibroblast growth factor receptor 1 gene locus amplification in resected
lung squamous cell carcinoma. J Thorac Oncol 2013 Nov;8(11):1371-1377 5. Schildhaus HU, Heukamp
LC, Merkelbach-Bruse S, et al: Definition of a fluorescence in-situ hybridization score identifies high-
and low-level FGFR1 amplification types in squamous cell lung cancer. Mod Pathol 2012
Nov;25(11):1473-1480
Useful For: An aid in identifying patients with myeloproliferative syndromes and the
t(8;var)(p11.2;var) translocation who therefore are likely resistant to current chemotherapies
Interpretation: A neoplastic clone is detected when the percent of cells with an abnormality exceeds
the normal cutoff for any given probe. The presence of a positive clone supports a diagnosis of
malignancy. The absence of an abnormal clone does not rule out the presence of neoplastic disorder.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Huret JL: FGFR1 (fibroblast growth factor receptor 1). Atlas Genet
Cytogenet Oncol Haematol December 2008, Available from URL:
http://AtlasGeneticsOncology.org/Genes/FGFR1113.html Accessed 4/6/2011 2. Patnaik MM, Gangat
N, Knudson RA, et al: Chromosome 8p11.2 translocations: prevalence, FISH analysis for FGFR1 and
MYST3, and clinicopathologic correlates in a consecutive cohort of 13 cases from a single institution.
Am J Hematol 2010;85:238-242 3. WHO Classification of Tumours of Hematopoietic and Lymphoid
Tissues. Edited by SH Swerdlow, E Campo, NL Harris, et al. Published by the International Agency for
Research on Cancer (IARC), 150 cours Albert Thomas, 69372 Lyon Cedex 08, France, 2008, pp 72-73
Useful For: Providing prognostic information and guiding treatment for patients with
cholangiocarcinomas and other tumor types including bladder, thyroid, oral cavity, and brain
Interpretation: A positive result is detected when the percent of cells with an abnormality exceeds
the normal cutoff for the probe set. A positive result suggests rearrangement of the FGFR2 locus and a
tumor that may be responsive to targeted FGFR2-inhibitor therapy. A negative result suggests no
rearrangement of the FGFR2 gene region at 10q26.1.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Mitesh BJ, Champion MD, Egan JB, et al: Integrated Genomic
Characterization Reveals Novel, Therapeutically Relevant Drug Targets in FGFR and EGFR Pathways
in Sporadic Intrahepatic Cholangiocarcinoma. PLOS Genetics 2014 Feb;10(2):e1004135 2. Graham RP,
Barr Fritcher EG, Pestova E, et al: Fibroblast growth factor receptor 2 translocations in intrahepatic
cholangiocarcinoma. Hum Pathol 2014 Aug;45(8):1630-1638 3. Arai Y, Totoki Y, Hosoda F, et al:
Fibroblast growth factor receptor 2 tyrosine kinase fusions define a unique molecular subtype of
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cholangiocarcinoma. Hepatology 2014;59:1427-1434 4. Wu YM, Su F, Kalyana-Sundaram S, et al:
Identification of targetable FGFR gene fusions in diverse cancers. Cancer Discov June
2013;3(6):636-647
Useful For: Confirming a diagnosis of fibrinogen alpha-chain (FGA) gene-related familial visceral
amyloidosis
Interpretation: All detected alterations are evaluated according to American College of Medical
Genetics recommendations.(1) Variants are classified based on known, predicted, or possible
pathogenicity and reported with interpretive comments detailing their potential or known significance.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for
standards of interpretation and reporting of sequence variations: revisions 2007. Genet Med
2008;10(4):294-300 2. Benson MD: The hereditary amyloidoses. Best Pract Res Clin Rhematol
2003;17:909-927 3. Benson MD: Ostertag revisited: The inherited systemic amyloidoses without
neuropathy. Amyloid 2005;12(2):75-87 4. Asselta R, Duga S, Tenchini ML: The molecular basis of
quantitative fibrinogen disorders. Thromb Haemost 2006 Oct;4(10):2115-2129 5. Shiller SM, Dogan A,
Highsmith WE: Laboratory methods for the diagnosis of hereditary amyloidoses. In
Amyloidosis-Mechanisms and Prospects for Therapy. Edited by S Sarantseva. InTech 2011, pp 101-120
Useful For: Evaluation of fibrinogen deficiency Measuring fibrinogen in patients with elevated
plasma levels of fibrin degradation products, patients receiving heparin, and in patients with antibodies
to thrombin (following surgical use of topical bovine thrombin) Identifiying afibrinogenemia,
hypofibrinogenemia and dysfibrinogenemia when ordered in combination with fibrinogen activity (FIB
/ Fibrinogen,Plasma)
Interpretation: This method measures the total amount of fibrinogen protein (ie, fibrinogen antigen)
present in the plasma. Adequate fibrinogen antigen levels in a context of low fibrinogen activity
suggests a dysfibrinogenemia. Fibrinogen antigen levels <100 mg/dL are associated with an increased
risk of bleeding.
Reference Values:
196-441 mg/dL
Interpretation: Fibrinogen may be decreased in acquired conditions such as liver disease and acute
intravascular coagulation and fibrinolysis and disseminated intravascular coagulation (ICF/DIC).
Fibrinogen may be decreased in rare conditions including congenital afibrinogenemia or
hypofibrinogenemia. Fibrinogen may be elevated with acute or chronic inflammatory conditions.
Reference Values:
200-393 mg/dL
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Clinical References: Mackie IJ, Kitchen S, Machin SJ, Lowe GD: Haemostais and Thrombosis Task
Force of the British Committee for standards in Haematology. Guidelines for fibrinogen assays. Br J
Haemotol 2003;121:396-304
Useful For: A preliminary step in obtaining cultured cells for genetic testing
Reference Values:
Not applicable
Clinical References:
Useful For: Producing fibroblast cultures that can be used for genetic analysis Once confluent flasks
are established, the fibroblast cultures are sent to other laboratories, either within Mayo Clinic or to
external sites, based on the specific testing requested.
Useful For: Diagnosing and monitoring oncogenic osteomalacia Possible localization of occult
neoplasms causing oncogenic osteomalacia Diagnosing X-linked hypophosphatemia or autosomal
dominant hypophosphatemic rickets Diagnosing familial tumoral calcinosis with hyperphosphatemia
Predicting treatment response to calcitriol or vitamin D analogs in patients with renal failure
Interpretation: The majority of patients with oncogenic osteomalacia have fibroblast growth factor
23 (FGF23) levels >2 times the upper limit of the reference interval. However, since the condition is a
rare cause of osteomalacia, a full baseline biochemical osteomalacia workup should precede FGF23
testing. This should include measurements of the serum concentrations of calcium, magnesium,
phosphate, alkaline phosphate, creatinine, parathyroid hormone (PTH), 25-hydroxy vitamin D
(25-OH-VitD), 1,25-2OH-VitD, and 24-hour urine excretion of calcium and phosphate. Findings
suggestive of oncogenic osteomalacia, which should trigger serum FGF23 measurements, are a
combination of normal serum calcium, magnesium, and PTH; normal or near normal serum
25-OH-VitD; low or low-normal serum 1,25-2OH-VitD; low-to-profoundly low serum phosphate; and
high urinary phosphate excretion. Once oncogenic osteomalacia has been diagnosed, the causative
tumor should be sought and removed. Complete removal can be documented by normalization of serum
FGF23 levels. Depending on the magnitude of the initial elevation, this should occur within a few hours
to a few days (half-life of FGF23 is approximately 20 to 40 minutes). Persistent elevations indicate
incomplete removal of tumor. Serial FGF23 measurements during follow-up may be useful for early
detection of tumor recurrence, or in partially cured patients, as an indicator of disease progression.
Because FGF23 has a short half-life, selective venous sampling with FGF23 measurements may be
helpful in localizing occult tumors in patients with oncogenic osteomalacia. However, the most useful
diagnostic cutoff for gradients between systemic and local levels has yet to be established. X-linked
hypophosphatemia (XLH) and most cases of autosomal dominant hypophosphatemic rickets (ADHR)
present before the age of 5 as vitamin D-resistant rickets. FGF23 is significantly elevated in the majority
of cases. Genetic testing provides the exact diagnosis. A minority of patients with ADHR may present
later, as older children, teenagers, or young adults. These patients may have clinical features and
biochemical findings, including FGF23 elevations, indistinguishable from oncogenic osteomalacia
patients. Genetic testing may be necessary to establish a definitive diagnosis. Patients with familial
tumoral calcinosis and hyperphosphatemia have loss-of-function FGF23 mutations. The majority of
these FGF23 mutant proteins are detected by FGF23 assays. The detected circulating levels are very
high, in a futile compensatory response to the hyperphosphatemia. Almost all patients with renal failure
have elevated FGF23 levels, and FGF23 levels are inversely related to the likelihood of successful
therapy with calcitriol or active vitamin D analogs. Definitive cutoffs remain to be established, but it
appears that renal failure patients with FGF23 levels of >50 times the upper limit of the reference range
have a low chance of a successful response to vitamin D analogues (<5% response rate).
Reference Values:
Results may be significantly elevated (ie, >900 RU/mL) in normal infants <3 months of age.
3 months-17 years: < or =230 RU/mL
> or =18 years: < or =180 RU/mL
Clinical References: 1. Online Mendelian Inheritance of Man (OMIM) entry *605380 Fibroblast
Growth Factor 23; FGF23, Retrieved 1/25/06, Available from URL:
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605380 2. Yu X, White KE: FGF23 and disorders
of phosphate homeostasis. Cytokine Growth Factor Rev 2005;16:221-232 3. Fukagawa M, Nii-Kono T,
Kazama JJ: Role of fibroblast growth factor 23 in health and chronic kidney disease. Curr Opin Nephrol
Hypertens 2005;14:325-329 4. Jan de Beur SM: Tumor-induced osteomalacia. JAMA
2005;294:1260-1267 5. Tenenhouse HS: Regulation of phosphorus homeostasis by the type IIa
Na/phosphate cotransporter. Ann Rev Nutr 2005;25:197-214
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Clinical Information: FGFR1 is a receptor tyrosine kinase that belongs to the fibroblast growth
factor family. FGFR1 amplification is seen in 13% to 22% of lung squamous cell carcinoma (SQCC) and
has been associated with a worse prognosis. For instance, FGFR1 expression in head and neck SQCC
correlates with poor histologic differentiation, wide invasion, and abundant nuclear pleomorphism.
Anti-FGFR inhibitors are now in early clinical trials and have shown to inhibit growth and induce
apoptosis in lung cancer cell lines.
Clinical References: 1. Nguyen PT, Tsunematsu T, Yanagisawa S, et al: The FGFR1 inhibitor
PD173074 induces mesenchymal-epithelial transition through the transcription factor AP-1. BJC
2013;109:2248-2258 2. Kohler LH, Mireskandari M, Knsel T, et al: FGFR1 expression and gene copy
numbers in human lung cancer. Virchows Arch 2012;461:49-57 3. Kim HR, Kim DJ, Kang DR, et al:
Fibroblast Growth Factor Receptor 1 Gene Amplification is Associated with Poor Survival and Cigarette
Smoking Dosage in Patients with Resected Squamous Cell Lung Cancer. Journal of Clinical Oncology
2013;31(6):731-737
Useful For: Aid in the diagnosis of identifying PRKACA gene rearrangements of patients with
fibrolamellar carcinoma
Interpretation: A positive result with the PRKACA probe is detected when the percent of cells with
an abnormality exceeds the normal cutoff for the probe set. A positive result of PRKACA suggests fusion
of the PRKACA and DNAJB1 genes at 19p13.1. A negative result suggests no fusion of the PRKACA
and DNAJB1 genes has occurred.
Reference Values:
An interpretive report will be provided.
Reference Values:
<0.35 kU/L
Interpretive Criteria:
<1:50 Negative
1.50-3.00 Equivocal
>3.00 Positive
This assay detects Filaria IgG4 associated with infections caused by the major filarial parasites,
including Dirofilaria immitis, Wuchereria brancrofti, Brugia malayi, and Onchocerca volvulus.
Detection of IgG4 subclass antibody offers enhanced specificity without sacrifice of sensitivity. Chronic
filarial infections manifesting as elephantiasis may not show a significant IgG4 response, and cannot be
ruled out by this assay. Equivocal results may represent cross-reactive antibodies induced by infection
with other nematodes.
Reference Values:
Negative
If positive, organism is identified.
Clinical References: Centers for Disease Control and Prevention, Division of Parasitic Diseases
and Malaria. DPDx, Diagnostic Procedures. 2013. Available at
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http://www.cdc.gov/dpdx/diagnosticProcedures/blood/specimencoll.html
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
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bronchospasm) in infants and children less than 5 years due to food sensitivity (milk, egg, soy, and wheat
proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: Prenatal screening for Down syndrome (nuchal translucency, pregnancy-associated plasma
protein A, human chorionic gonadotropin) and trisomy 18 (nuchal translucency, pregnancy-associated
plasma protein A, human chorionic gonadotropin)
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 864
Interpretation: Screen-Negative: A screen-negative result indicates that the calculated screen risk is
below the established cutoff of 1/230 for Down syndrome and 1/100 for trisomy 18. A negative screen
does not guarantee the absence of trisomy 18 or Down syndrome. Screen-negative results typically do
not warrant further evaluation. Screen-Positive: When a Down syndrome risk cutoff of 1/230 is used for
follow-up, the combination of maternal age, pregnancy-associated plasma protein A, human chorionic
gonadotropin, and nuchal translucency has an overall detection rate of approximately 85% with a
false-positive rate of 5% to 10%. In practice, both the detection rate and false-positive rate increase with
age, thus detection and positive rates will vary depending on the age distribution of the screening
population.
Reference Values:
DOWN SYNDROME
Calculated screen risks <1/230 are reported as screen negative.
Risks > or =1/230 are reported as screen positive.
TRISOMY 18
Calculated screen risks <1/100 are reported as screen negative.
Risks > or =1/100 are reported as screen positive. A numeric risk for trisomy 18 risk is provided with
positive results on non-diabetic, non-twin pregnancies.
Clinical References: 1. Malone FD, Canick JA, Ball RH, et al: First-trimester or second-trimester
screening, or both, for Down's syndrome. N Engl J Med 2005 Nov 10;353(19):2001-2011 2. Screening
for fetal chromosomal abnormalities. ACOG Practice Bulletin No. 77. American College of
Obstetricians and Gynecologists. Obstet Gynecol 2007;109:21727 3. Wald NJ, Rodeck C, Hackshaw
AK, Rudnicka A: SURUSS in Perspective. Semin Perinatol 2005;29:225-235
Codfish/Scrod IgG
Crab IgG
Lobster IgG
Oyster IgG
Salmon IgG
Sardine/Pilchard IgG
Shrimp IgG
Sole IgG
Trout IgG
Tuna IgG The reference range listed on the report is the lower limit
of quantitation for the assay. The clinical utility of
food-specific IgG tests has not been established. These
tests can be used in special clinical situations to select
foods for evaluation by diet elimination and challenge in
patients who have food-related complaints. It should be
recognized that the presence of food-specific IgG alone
cannot be taken as evidence of food allergy and only
indicated immunologic sensitization by the food allergen
in question. This test should only be ordered by
physicians who recognize the limitations of the test.
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FLEC Flecainide, Serum
9243 Clinical Information: Flecainide (Tambocor) is a class I cardiac antiarrhythmic agent with
electrophysiologic properties similar to lidocaine, quinidine, procainamide, and tocainide. Flecainide
produces a dose-related decrease in intracardiac conduction in all parts of the heart, with the greatest
effect on the His-Purkinje system. Atrial effects are limited. Flecainide causes a dose-related and plasma
concentration-related decrease in single and multiple premature ventricular contractions and can suppress
recurrence of ventricular tachycardia. Flecainide is eliminated from blood by hepatic metabolism as well
as renal clearance; significant changes in either organ system will cause impaired clearance. During
preclinical trials, patients with congestive heart failure were observed to have radically altered clearance
properties. Cardiac toxicity attributed to flecainide is related to its cardiac conduction slowing properties.
Excessive prolongation of PR, QRS, and QT intervals occurs with increased amplitude of the T wave.
Reductions in myocardial rate, contractility, as well as conduction disturbances, are also associated with
excessive dose and plasma concentration of flecainide. Death can occur from hypotension, respiratory
failure, and asystole. Flecainide is contraindicated in patients with sick sinus syndrome. It causes sinus
bradycardia, sinus pause, or sinus arrest.
Reference Values:
0.2-1.0 mcg/mL
Clinical References: 1. Burtis CA, Ashwood ER, Bruns DE, et al: Tietz Textbook of Clinical
Chemistry and Molecular Diagnosis (Fifth edition), Elsevier, St. Louis, USA, 2012 2. Josephson ME,
Buxton AE, Marchlinski FE: The tachyarrhythmias: tachycardias. In Harrison's Principles of Internal
Medicine. 12th edition. Edited by JD Wilson, E Braunwald, KJ Isselbacher, et al: New York,
McGraw-Hill Book Company, 1991, p 915
Interpretation: All detected alterations are evaluated according to American College of Medical
Genetics recommendations.(1) Variants are classified based on known, predicted, or possible
pathogenicity and reported with interpretive comments detailing their potential or known significance.
Reference Values:
Interpretive report will be provided.
Clinical References: 1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for
standards for interpretation and reporting of sequence variations: Revisions 2007. Genet Med
2008;10(4):294-300 2. Smith FJD, Irvine AD, Terron-Kwiatkowski A, et al: Loss-of-function mutations
in the gene encoding filaggrin cause ichthyosis vulgaris. Nat Genet 2006;38:337-342 3. Thyssen JP,
Godoy-Gijon E, Elias PM: Ichthyosis vulgaris-the filaggrin mutation disease. Br J Dermatol 2013
Jun;168(6):1155-1166 4. Palmer CN, Irvine AD, Terron-Kwiatkowski A, et al: Common
loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for
atopic dermatitis. Nat Genet 2006 Apr;38(4):441-446
Useful For: An aid in phenotyping endothelial-derived tumors, Ewing sarcoma, Merkel cell
carcinoma, lung adenocarcinoma, melanoma, and erythroleukemia
Interpretation: This test includes only technical performance of the stain (no pathologist
interpretation is performed). If diagnostic consultation by a pathologist is required order 70012 /
Pathology Consultation. The positive and negative controls are verified as showing appropriate
immunoreactivity. If a control tissue is not included on the slide, a scanned image of the relevant quality
control tissue is available upon request. Please contact 1-855-516-8404. Interpretation of this test should
be performed in the context of the patient's clinical history and other diagnostic tests by a qualified
pathologist.
Clinical References: 1. Folpe AL, Hill CE, Parham DM, et al: A study of 132 round cell tumors
with emphasis on CD99-positive mimics of Ewing's sarcoma/primitive neuroectodermal tumor. Am J
Surg Pathol 2000;24(12):1657-1662 2. Pusztaszeri MP, Seelentag W, Bosman FT, et al:
Immuno-histochemical expression of endothelial markers CD31, CD34, von Willebrand factor and fli-1
in normal human tissues. J Histochem Cytochem 2006;54:385-395 3. Folpe AL, Chand EM, Goldblum
JR, et al: Expression of fli-1, a nuclear transcription factor, distinguishes vascular neoplasms from
potential mimics. AM J Surg Pathol 2001;25(8):1061-1066
Reference Values:
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<0.35 kU/L
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Levis M, Small D: FLT3: ITDoes matter in leukemia. Leukemia 2003
September;17:1738-1752 2. Gilliland DG, Griffin JD: The roles of FLT3 in hematopoiesis and leukemia.
Blood 2002 September 1;100(5):1532-1542
FL Fluoride, Plasma
8641 Clinical Information: Fluoride induces bone formation by stimulating osteoblasts. Because fluorides
increase bone density, they are used in dental preparations and as an antiosteoporotic agent. However,
prolonged high exposure to fluoride produces changes in bone morphology consistent with osteomalacia,
including prolonged mineralization lag time and increased osteoid thickness. The adverse skeletal effects
of fluoride are associated with plasma fluoride >4 mcmol/L. Chronic fluorosis may produce
osteosclerosis, periostitis, calcification of ligaments and tendons, and crippling deformities. Prolonged
exposure to the fluoride-containing antifungal agent voriconazole can produce high plasma fluoride
concentrations and bone changes (periostitis).
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Useful For: Assessing accidental fluoride ingestion Monitoring patients receiving sodium fluoride
for bone disease or patients receiving voriconazole therapy
Interpretation: Humans exposed to fluoride-treated water typically have plasma fluoride in the
range of 1 to 4 mcmol/L. Those who are not drinking fluoride-treated water have plasma fluoride <1
mcmol/L. Plasma fluoride values >4 mcmol/L indicate excessive exposure and are associated with
periostitis.
Reference Values:
0.0-4.0 mcmol/L
Clinical References: 1. Cardos VES, Whitford GH, Aoyama H, et al: Daily variations in human
plasma fluoride concentrations. J Fluorine Chem 2008:129;1193-1198 2. Wermers RA, Cooper K,
Razonable RR, et al: Long term use of voriconazole, a fluoride containing medication, is associated
with periostitis, fluorosis, and fluoride excess in transplant patients. Clin Infect Dis 2011;52:604-611
Useful For: Identifying individuals at increased risk of toxicity when considering 5-fluorouracil
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 869
(5-FU) and capecitabine chemotherapy treatment Variations detected in the DPYD gene are also
associated with dihydropyrimidine dehydrogenase (DPD) deficiency(4)
Interpretation: Evaluation and categorization of variants is performed using the most recent published
American College of Medical Genetics recommendations as a guideline.(6) Variants are classified based
on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their
potential or known significance.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Caudle KE, Thorn CF, Klein TE, et al: Clinical Pharmacogenetics
Implementation Consortium guidelines for dihydropyrimidine dehydrogenase genotype and
fluoropyrimidine dosing. Clin Pharmacol Ther 2013;94(6):640-645 2. Morel A, Boisdron-Celle M, Fey L,
et al: Clinical relevance of different dihyropyrimidine dehydrogenase gene single nucleotide
polymorphisms on 5-fluorouracil tolerance. Mol Cancer Ther 2006 Nov;5(11):2895-2904 3. FDA Table
of Pharmacogenomic Biomarkers in Drug Labeling. Available at:
http://www.fda.gov/drugs/scienceresearch/researchareas/pharmacogenetics/ucm083378.htm 4.
Dihydropyrimidine Dehydrogenase Deficiency (#274270) In Online Mendelian Inheritance in Man.
Available at www.omim.org 5. Lecomte T, Ferraz JM, Zinzindohoue F, et al: Thymidylate synthase gene
polymorphism predicts toxicity in colorectal cancer patients receiving 5-fluorouracil-based chemotherapy.
Clin Cancer Res 2004;10:5880-5888 6. Richards CS, Bale S, Bellissimo DB, et al: ACMG
recommendations for standards of interpretation and reporting of sequence variations: revisions 2007.
Genet Med 2008;10(4):294-300 7. Offer SM, Fossum CC, Wegner NJ, et al: Comparative functional
analysis of DPYD variants of potential clinical relevance to dihydropyrimidine dehydrogenase activity.
Cancer Res 2014;74(9):2545-2554
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3RG c.-58_-31del28 2R Decreased expression Increased risk for toxicity Possible improved tumor
response c.-58G->C rs2853542 c.-86G->C rs183205964 * Other or novel variations, besides those listed
here, may also impact fluoropyrimidine related side effects and tumor response. The DPYD gene is
located on chromosome 1 and contains 2 transcripts. The longest transcript (NM_000110.3) contains 23
exons, and the shortest transcript (NM_001160301.1) contains 6 exons, with exon 6 being unique to this
transcript. All exons (total of 24 from both transcripts), and exon-intron boundaries are assessed. The
TYMS gene is located on chromosome 18 and contains 7 exons (transcript NM_001071.2). The 5' UTR
region is assessed. Genetic variations involved in the metabolic pathway of fluoropyrimidines have been
shown to contribute to the differences in clinical outcomes including toxicity and tumor response.
Useful For: Identifying individuals at increased risk of toxicity when considering 5-fluorouracil
(5-FU) and capecitabine chemotherapy treatment Variations detected in the DPYD gene are also
associated with dihydropyrimidine dehydrogenase (DPD) deficiency(4) Genotyping patients who prefer
not to have venipuncture done
Interpretation: Evaluation and categorization of variants is performed using the most recent
published American College of Medical Genetics recommendations as a guideline.(6) Variants are
classified based on known, predicted, or possible pathogenicity and reported with interpretive comments
detailing their potential or known significance.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Caudle KE, Thorn CF, Klein TE, et al: Clinical Pharmacogenetics
Implementation Consortium guidelines for dihydropyrimidine dehydrogenase genotype and
fluoropyrimidine dosing. Clin Pharmacol Ther 2013;94(6):640-645 2. Morel A, Boisdron-Celle M, Fey
L, et al: Clinical relevance of different dihyropyrimidine dehydrogenase gene single nucleotide
polymorphisms on 5-fluorouracil tolerance. Mol Cancer Ther 2006 Nov;5(11):2895-2904 3. FDA Table
of Pharmacogenomic Biomarkers in Drug Labeling. Available at:
http://www.fda.gov/drugs/scienceresearch/researchareas/pharmacogenetics/ucm083378.htm 4.
Dihydropyrimidine Dehydrogenase Deficiency (#274270) In Online Mendelian Inheritance in Man.
Available at www.omim.org 5. Lecomte T, Ferraz JM, Zinzindohoue F, et al: Thymidylate synthase
gene polymorphism predicts toxicity in colorectal cancer patients receiving 5-fluorouracil-based
chemotherapy. Clin Cancer Res 2004;10:5880-5888 6. Richards CS, Bale S, Bellissimo DB, et al:
ACMG recommendations for standards of interpretation and reporting of sequence variations: revisions
2007. Genet Med 2008;10(4):294-300 7. Offer SM, Fossum CC, Wegner NJ, et al: Comparative
functional analysis of DPYD variants of potential clinical relevance to dihydropyrimidine
dehydrogenase activity. Cancer Res 2014;74(9):2545-2554
Useful For: Monitoring serum concentration of fluoxetine during therapy Evaluating potential
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toxicity Evaluating patient compliance
Interpretation: Most individuals display optimal response to fluoxetine when combined serum levels
of fluoxetine and norfluoxetine are between 120 and 300 ng/mL. Some individuals may respond well
outside of this range, or may display toxicity within the therapeutic range, thus interpretation should
include clinical evaluation. A toxic range has not been well established.
Reference Values:
Fluoxetine + norfluoxetine: 120-300 ng/mL
Clinical References: 1. Wille SM, Cooreman SG, Neels, HM, Lambert WE: Relevant issues in the
monitoring and toxicology of antidepressants. Crit Rev Clin Lab Sci 2008;45(1):25-89 2. Baumann P,
Hiemke C, Ulrich S, et al: The AGNP-TDM expert group consensus guidelines: therapeutic drug
monitoring in psychiatry. Pharmacopsychiatry 2004;37:243-265
Desalkylflurazepam:
Reference Range: 30 - 150 ng/mL
Flurazepam + Desalkyflurazepam:
Reference Range: 30 - 180 ng/mL
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increased water solubility such that it is excreted in urine. Accordingly, fluticasone 17-beta-carboxylic
acid is detected in urine in individuals recently exposed to inhaled FP therapy. Fluticasone
17-beta-carboxylic acid may be detected in urine as early as 16 to 24 hours following a patient's first
administration of low dose (220 mcg) FP therapy. The window of detection for fluticasone
17-beta-carboxylic acid is 6 days following cessation of FP therapy.
Useful For: Assessing compliance (recent exposure) to fluticasone propionate therapy An aid in the
evaluation of secondary adrenal insufficiency
Reference Values:
Negative
Cutoff concentration: 10 pg/mL
Values for normal patients not taking fluticasone propionate should be less than the cutoff
concentration (detection limit).
Clinical References: 1. Pearce RE, Leeder JS, Kearns GL: Biotransformation of fluticasone: in
vitro characterization. Drug Metab Dispos 2006;34:1035-1040 2. Paton J, Jardine E, McNeill E, et al:
Adrenal responses to low dose synthetic ACTH (Synacthen) in children receiving high dose inhaled
fluticasone. Arch Dis Child 2006;91:808-813 3. Callejas SL, Biddlecombe RA, Jones AE, et al:
Determination of the glucocorticoid fluticasone propionate in plasma by automated solid-phase
extraction and liquid chromatography-tandem mass spectrometry. J Chromatogr B Biomed Sci Appl
1998;718:243-250 4. Bender BG, Bartlett SJ, Rand CS, et al: Impact of interview mode on accuracy of
child and parent report of adherence with asthma-controller medication. Pediatrics. 2007;120:e471-477
5. National Asthma Education and Prevention Program: Expert Panel Report 3 (EPR-3): Guidelines for
the Diagnosis and Management of Asthma-Summary Report 2007. J Allergy Clin Immunol. 2007
Nov;120(5 Suppl):S94-138
Reference Values:
> or =4.0 mcg/L
<4.0 mcg/L suggests folate deficiency
Clinical References: 1. Fairbanks VF, Klee GG: Biochemical aspects of hematology. In Tietz
Textbook of Clinical Chemistry. Edited by CA Burtis, ER Ashwood. Philadelphia, WB Saunders
Company, 1999, pp 1690-1698 2. George L, Mills JL, Johansson AL, et al: Plasma folate levels and risk
of spontaneous abortion. JAMA 2002 October 16;288:1867-1873 3. Klee GG: Cobalamin and folate
evaluation: measurement of methylmalonic acid and homocysteine vs vitamin B12 and folate. Clin Chem
2000 August;46(8 Pt 2):1277-1283 4. Benoist BD: Conclusions of a WHO Technical Consultation on
folate and vitamin B12 deficiencies. Food and Nutrition Bulletin 2008 (volume 29, number 2) S238-S244
Clinical References: 1. Hamid Z, Mrak RE, Ijaz MT, Faas FH: Sensitivity and specificity of
immunohistochemistry in pituitary adenomas. The Endocrinologist 2009;19(1):38-43 2. Osamura RY,
Kajiya H, Takei M, et al: Pathology of the human pituitary adenomas. Histochem Cell Biol
2008;130(3):495-507 3. Osamura RY, Watanabe K: Immunohistochemical studies of human FSH
producing pituitary adenomas. Virchows Archiv A 1988;413(1):61-68 4. Pawlikowski M, Pisarek H,
Kubiak R. et al: Immunohistochemical detection of FSH receptors in pituitary adenomas and adrenal
tumors. Folia Histochem Cytobiol 2012;50(3):325-330
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FSH Follicle-Stimulating Hormone (FSH), Serum
8670 Clinical Information: Gonadotropin-releasing hormone from the hypothalamus controls the
secretion of the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from
the anterior pituitary. The menstrual cycle is divided by a midcycle surge of both FSH and LH into a
follicular phase and a luteal phase. FSH appears to control gametogenesis in both males and females.
Useful For: An adjunct in the evaluation of menstrual irregularities Evaluating patients with
suspected hypogonadism Predicting ovulation Evaluating infertility Diagnosing pituitary disorders
Interpretation: In both males and females, primary hypogonadism results in an elevation of basal
follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels. FSH and LH are generally
elevated in: -Primary gonadal failure -Complete testicular feminization syndrome -Precocious puberty
(either idiopathic or secondary to a central nervous system lesion) -Menopause (postmenopausal FSH
levels are generally >40 IU/L) -Primary ovarian hypofunction in females -Primary hypogonadism in
males Normal or decreased FSH in: -Polycystic ovary disease in females FSH and LH are both
decreased in failure of the pituitary or hypothalamus.
Reference Values:
Males
1-7 days: < or =3.0 IU/L
8-14 days: < or =1.4 IU/L
15 days-3 years: < or =2.5 IU/L
4-6 years: < or =6.7 IU/L
7-8 years: < or =4.1 IU/L
9-10 years: < or =4.5 IU/L
11 years: 0.4-8.9 IU/L
12 years: 0.5-10.5 IU/L
13 years: 0.7-10.8 IU/L
14 years: 0.5-10.5 IU/L
15 years: 0.4-18.5 IU/L
16 years: < or =9.7 IU/L
17 years: 2.2-12.3 IU/L
> or =18 years: 1.0-18.0 IU/L
TANNER STAGES*
Stage l: < or =3.7 IU/L
Stage ll: < or =12.2 IU/L
Stage lll: < or =17.4 IU/L
Stage lV: 0.3-8.2 IU/L
Stage V: 1.1-12.9 IU/L
*Puberty onset occurs for boys at a median age of 11.5 (+/- 2) years. For boys there is no proven
relationship between puberty onset and body weight or ethnic origin. Progression through Tanner stages
is variable. Tanner stage V (adult) should be reached by age 18.
Females
1-7 days: < or =3.4 IU/L
8-14 days: < or =1.0 IU/L
15 days-6 years: < or =3.3 IU/L
7-8 years: < or =11.1 IU/L
9-10 years: 0.4-6.9 IU/L
11 years: 0.4-9.0 IU/L
12 years: 1.0-17.2 IU/L
13 years: 1.8-9.9 IU/L
14-16 years: 0.9-12.4 IU/L
17 years: 1.2-9.6 IU/L
> or =18 years:
Premenopausal
Follicular: 3.9-8.8 IU/L
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Midcycle: 4.5-22.5 IU/L
Luteal: 1.8-5.1 IU/L
Postmenopausal: 16.7-113.6 IU/L
TANNER STAGES*
Stage l: 0.4-6.7 IU/L
Stage ll: 0.5-8.7 IU/L
Stage lll: 1.2-11.4 IU/L
Stage lV: 0.7-12.8 IU/L
Stage V: 1.0-11.6 IU/L
*Puberty onset (transition from Tanner stage I to Tanner stage II) occurs for girls at a median age of
10.5 (+/- 2) years. There is evidence that it may occur up to 1 year earlier in obese girls and in African
American girls. Progression through Tanner stages is variable. Tanner stage V (adult) should be reached
by age 18.
Pediatric ranges derived for DXI method from analytic comparison to reference method in: Elmlinger
MW, Kuhnel W, Ranke MB: Reference ranges for serum concentrations of lutropin (LH), follitropin
(FSH), estradiol (E2), prolactin, progesterone, sex hormone-binding globulin (SHBG),
dehydroepiandrosterone sulfate (DHEAS), cortisol and ferritin in neonates, children and young adults.
Clin Chem Lab Med 2002;40(11):1151-1160
Clinical References: 1. Demers LM, Vance ML: Pituitary function. In Tietz Textbook of Clinical
Chemistry and Molecular Diagnostics. Fourth edition. Edited by CA Burtis, ER Ashwood, DE Bruns. St.
Louis: Elsevier Saunders Company, 2006, pp 1984-1989 2. Haymond S, Gronowski AM: Reproductive
related disorders. In Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Fourth edition.
Edited by CA Burtis, ER Ashwood, DE Bruns. St. Louis: Elsevier Saunders Company, 2006, pp 2101
-2127 3. Instruction manual: UniCel DXI 800 FSH Assay. Beckman Coulter, Inc., Fullerton, CA, 2010
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
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1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 877
Saunders Company, New York, 2007, Part VI, pp 961-971
Peanut IgG4
Soybean IgG4
Wheat IgG4
Yeast (Saccharomyces cerevisiae) IgG4 The reference range listed on the report is the lower limit
of quantitation for the assay. The clinical utility of
food-specific IgG4 tests has not been clearly established.
These tests can be used in special clinical situations to
select foods for evaluation by diet elimination and
challenge in patients who have food-related complaints,
and to evaluate food allergic patients prior to food
challenges. The presence of food-specific IgG4 alone
cannot be taken as evidence of food allergy and only
indicates immunologic sensitization to the food allergen
in question.
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical utility
of food-specific IgG tests has not been established. These tests can be used in special clinical situations to
select foods for evaluation by diet elimination and challenge in patients who have food-related
complaints. It should be recognized that the presence of food-specific IgG alone cannot be taken as
evidence of food allergy and only indicates immunologic sensitization by the food allergen in question.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 878
This test should only be ordered by physicians who recognize the limitations of the test.
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 879
bronchospasm) in infants and children less than 5 years due to food sensitivity (milk, egg, soy, and
wheat proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 881
6 > or =100 Strongly positive Reference values
apply to all ages.
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 882
immunoglobulin E (IgE)-sensitized effector cells (mast cells and basophils) when cell-bound IgE
antibodies interact with allergen. In vitro serum testing for IgE antibodies provides an indication of the
immune response to allergen(s) that may be associated with allergic disease. The allergens chosen for
testing often depend upon the age of the patient, history of allergen exposure, season of the year, and
clinical manifestations. In individuals predisposed to develop allergic disease(s), the sequence of
sensitization and clinical manifestations proceed as follows: eczema and respiratory disease (rhinitis and
bronchospasm) in infants and children less than 5 years due to food sensitivity (milk, egg, soy, and wheat
proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Formic acid is a metabolite of Formaldehyde and an index of exposure to Formaldehyde and (other)
precursors.
Creatinine (mg/L)
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 883
U.S. Population (10th 90th percentiles, median)
All participants:
335 - 2370 mg/L, median: 1180 (n=22,245)
Males:
495 - 2540 mg/L, median: 1370 (n=10,610)
Females:
273 - 2170 mg/L, median 994 (n=11,635)
Reference Values:
An interpretative report will be provided.
Clinical References: 1. Shah SP, Kobel M, Senz J, et al: Mutation of FOXL2 in granulosa-cell
tumors of the ovary. N Engl J Med 2009;360:2719-2729 2. Kim MS, Hur SY, Yoo NJ, et al: Mutational
analysis of FOXL2 codon 134 in granulosa cell tumour of ovary and other human cancers. J Pathol
2010;221:147-152 3. Schrader KA, Gorbatcheva B, Senz J, et al: The specificity of the FOXL2
c.402C->G somatic mutation: a survey of solid tumors. PLoS One 2009 Nov 24;4(11):e7988 4. Benayoun
BA, Kalfa N, Sultan C, et al: The forkhead factor FOXL2: a novel tumor suppressor? Biochim Biophys
Acta 2010;1805:1-5
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 884
is performed). If diagnostic consultation by a pathologist is required order 70012 / Pathology
Consultation. The positive and negative controls are verified as showing appropriate immunoreactivity. If
a control tissue is not included on the slide, a scanned image of the relevant quality control tissue is
available upon request. Please contact 1-855-516-8404. Interpretation of this test should be performed in
the context of the patient's clinical history and other diagnostic tests by a qualified pathologist.
Clinical References: 1. Choi WWL, Weisenburger DD, Greiner TC, et al: A new immunostain
algorithm classifies diffuse large b-cell lymphoma into molecular subtypes with high accuracy. Clin
Cancer Res 2009;15(17):5494-5502 2. Hoeller S, Schneider Au, Haralambieva E, et al: FOXP1 protein
overexpression is associated with inferior outcome in nodal diffuse large b-cell lymphomas with
non-germinal centre phenotype, independent of gains and structural aberrations at 3p14.1.
Histopathology 2010;57:73-80 3. Hans CP, Weisenburger DD, Greiner TC, et al: Confirmation of the
molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue
microarray. Blood 2004;103(1):275-282
Clinical References: 1. Katho M, Katoh M: Human FOX gene family. Int J Oncol 2004
November;25(5):1495-1500 2. Karube K, Ohshima K, Tsuchiya T, et al: Expression of FOXP3, a key
molecule in CD4CD25 regulatory T cells, in adult T-cell leukaemia/lymphoma cells. Br J Haematol
2004 July;126(1):81-84 3. Roncador G, Garcia JF, Garcia JR, et al: FOXP3, a selective marker for a
subset of adult T-cell leukaemia/lymphoma. Leukemia 2005 December;19(12):2247-2253
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 885
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: Determination of carrier status for individuals with a family history of fragile X
syndrome or X-linked mental retardation Confirmation of a diagnosis of fragile X syndrome, fragile X
tremor/ataxia syndrome, or premature ovarian failure caused by expansions in the FMR1 gene Prenatal
diagnosis of fragile X syndrome when there is a documented FMR1 expansion in the family
Clinical References: 1. Jacquemont S, Hagerman RJ, Hagerman PJ, Leehey MA: Fragile-X
syndrome and fragile X-associated tremor/ataxia syndrome: two faces of FMR1. Lancet Neurol
2007;6(1):45-55 2. Mc-Conkie-Rosell A, Finucane B, Cronister A, et al: Genetic counseling for fragile
X Syndrome: updated recommendations of the National Society of Genetic Counselors. J Genet Couns
2005;14(4):249-270 3. Sherman S, Pletcher BA, Driscoll DA: Fragile X syndrome: diagnostic and
carrier testing (ACMG Practice Guideline). Genet Med 2005;7:584-587
This follow-up test is added by the laboratory dependent upon on the result of the PCR analysis (FXS /
Fragile X Syndrome, Molecular Analysis).
Interpretive Criteria:
<1:20 Negative
1:20 - 1:80 Equivocal
> or =1:160 Positive
In the presence of compatible symptoms, a Francisella tularensis antibody titer of 1:160 or greater in
an acute specimen supports a presumptive diagnosis of tularemia. However, a titer > or =1:160 may also
reflect past infection. An equivocal titer may be due to crossreactive antibodies (Brucella, Yersinia, or
Proteus OX19), past infection, or very recent infection. A four-fold rise in titer between acute and
convalescent sera is required for definitive serologic diagnosis of tularemia.
Interpretation: Abnormally high levels of free fatty acids are associated with uncontrolled diabetes
mellitus and with conditions that involve excessive release of a lipoactive hormone such as epinephrine,
norepinephrine, glucagon, thyrotropin, and adrenocorticotropin.
Reference Values:
> or =16 years: 0.00-0.72 mmol/L
Reference values have not been established for patients who are <16 years of age.
Clinical References: 1. Dole VP: A relation between non-esterified fatty acids in plasma and the
metabolism of glucose. J Clin Invest 1956;35:150-154 2. Imrie H, Abbas A, Kearney M: Insulin
resistance, lipotoxicity and endothelial dysfunction. Biochim Biophys Acta, 2010 Mar;1801 (3):320-326
Useful For: Estimating the amount of circulating free thyroxine (free thyroxine index) using the total
thyroxine and thyroid binding capacity (T-uptake)
Interpretation: The free thyroxine index (FTI) is determined by the following calculation: FTI =
Thyroxine (T4)/Thyroid Binding Capacity The FTI is a normalized determination that remains relatively
constant in healthy individuals and compensates for abnormal levels of binding proteins. Hyperthyroidism
causes increased FTI and hypothyroidism causes decreased values.
Reference Values:
Thyroxine Binding Capacity (units are in Thyroxine Binding Index [TBI]):
0-19 years: 0.8-1.2 TBI
> or =20 years: 0.8-1.3 TBI
T4 Total (T4):
0-5 days: 5.0-18.5 mcg/dL
6 days-2 months: 5.4-17.0 mcg/dL
3-11 months: 5.7-16.0 mcg/dL
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1-5 years: 6.0-14.7 mcg/dL
6-10 years: 6.0-13.8 mcg/dL
11-19 years: 5.9-13.2 mcg/dL
> or =20 years: 4.5-11.7 mcg/dL
Clinical References: 1. Whitley RJ, Meikle AW, Watts NB: Thyroid function. In Tietz
Fundamentals of Clinical Chemistry. Fourth edition. Edited by CA Burtis, ER Ashwood. Philadelphia,
WB Saunders Company, 1996, pp 645-646 2. Wilson JD, Foster DW, Kronenburg MD, et al: Williams
Textbook of Endocrinology. Ninth edition, WB Saunders Company, 1998, pp 407-477
Useful For: Aids in the diagnosis of primary amebic meningoencephalitis and granulomatous amebic
encephalitis in spinal fluid and tissue in conjunction with clinical findings
Interpretation: A positive result indicates the presence of free-living amoeba DNA and is consistent
with active or recent infection. While positive results are highly specific indicators of disease, they
should be correlated with symptoms and clinical findings of primary amebic meningoencephalitis and
granulomatous amebic encephalitis.
Reference Values:
Negative
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FFRED Friedreich Ataxia Repeat Expansion Analysis - Unknown
91819 Mutation
Reference Values:
A final report will be attached in MayoAccess.
Useful For: Diagnosing individuals with Friedreich ataxia in blood spot specimens Monitoring frataxin
levels in patients with Friedreich ataxia
Interpretation: Normal results (> or =15 ng/mL for pediatric and > or =21 ng/mL for adult patients) in
properly submitted specimens are not consistent with Friedreich ataxia. For results outside the normal
reference range an interpretative comment will be provided.
Reference Values:
Pediatric (<18 years) normal frataxin: > or =15 ng/mL
Adults (> or =18 years) normal frataxin: > or =21 ng/mL
Clinical References: 1. Deutsch EC, Oglesbee D, Greeley NR, Lynch DR: Usefulness of frataxin
immunoassays for the diagnosis of Friedreich ataxia. J Neurol Neurosurg Psychiatry 2014
Sep;85(9):994-1002 2. Babady NE, Carelle N, Wells RD, et al: Advancements in the pathophysiology of
Friedreich ataxia and new prospects for treatments. Mol Genet Metab 2007;92:23-35 3. Boehm T,
Scheiber-Mojdehkar B, Kluge B, et al: Variations of frataxin protein levels in normal individuals. Neurol
Sci 2011 Apr;32(2):327-30 doi: 10.1007/s10072-010-0326-1
Useful For: Diagnosing individuals with Friedreich ataxia in whole blood specimens Monitoring
frataxin levels in patients with Friedreich ataxia
Interpretation: Normal results (> or =19 ng/mL for pediatric and > or =21 ng/mL for adult patients)
in properly submitted specimens are not consistent with Friedreich ataxia. For results outside the normal
reference range an interpretative comment will be provided.
Reference Values:
Pediatric (<18 years) normal frataxin: > or =19 ng/mL
Adults (> or =18 years) normal frataxin: > or =21 ng/mL
Clinical References: 1. Deutsch EC, Oglesbee D, Greeley NR, Lynch DR: Usefulness of frataxin
immunoassays for the diagnosis of Friedreich ataxia. J Neurol Neurosurg Psychiatry 2014
Sep;85(9):994-1002 2. Babady NE, Carelle N, Wells RD, et al: Advancements in the pathophysiology
of Friedreich ataxia and new prospects for treatments. Mol Genet Metab 2007;92:23-35 3. Boehm T,
Scheiber-Mojdehkar B, Kluge B, et al: Variations of frataxin protein levels in normal individuals.
Neurol Sci 2011 Apr;32(2):327-330 doi: 10.1007/s10072-010-0326-1
Reference Values:
200-285 mcmol/L
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FROS Fructose, Semen or Seminal Plasma
81164 Clinical Information: Fructose is produced in the male reproductive tract by the seminal vesicles and
is released into the semen during ejaculation. Fructose is the energy source for sperm motility.
Useful For: Fructose testing should be considered for patients with azoospermia and low volume
ejaculates to establish the origin of the azoospermia.
Reference Values:
Positive
Clinical References: Lipshultz LI, Howards SS: Infertility in the Male. Second edition. Edited by
DK Marshall. St. Louis, MO, Mosby-Year Book, Inc., 1991, pp 133-135, 194, 209
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical utility
of food-specific IgG tests has not been established. These tests can be used in special clinical situations to
select foods for evaluation by diet elimination and challenge in patients who have food-related
complaints. It should be recognized that the presence of food-specific IgG alone cannot be taken as
evidence of food allergy and only indicates immunologic sensitization by the food allergen in question.
This test should only be ordered by physicians who recognize the limitations of the test.
Useful For: Second-tier test for confirming glutamate formiminotransferase deficiency (indicated by
biochemical testing or newborn screening) Ruling out other diseases associated with high levels of urine
formiminoglutamate Carrier screening in cases where there is a family history of glutamate
formiminotransferase deficiency but disease-causing mutations have not been identified in an affected
individual
Interpretation: All detected alterations are evaluated according to American College of Medical
Genetics recommendations.(1) Variants are classified based on known, predicted, or possible
pathogenicity and reported with interpretive comments detailing their potential or known significance.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for
standards of interpretation and reporting of sequence variations: revisions 2007. Genet Med
2008;10(4):294-300 2. Hilton JF, Christensen KE, Watkins D, et al: The molecular basis of glutamate
formiminotransferase deficiency. Hum Mutat 2003;22:67-73 3. Solans A, Estivill X, de la Luna S:
Cloning and characterization of human FTCD on 21q22.3, a candidate gene for glutamate
formiminotransferase deficiency. Cytogenet Cell Genet 2000;88:43-49
Useful For: Diagnosis and treatment of the etiologic agents of fungemia Select patient population
that presents with signs and symptoms of sepsis, especially fever of unknown origin
Interpretation: Positive cultures of yeast and filamentous fungi are reported with the organism
identification. Positive cultures are usually an indication of infection and are reported as soon as
detected. Correlation of culture results and the clinical situation is required for optimal patient
management. A final negative report is issued after 30 days of incubation.
Reference Values:
Negative
If positive, notification is made as soon as the positive culture is detected or identified.
Clinical References: 1. Reimer LG, Wilson ML, Weinstein MP: Update on detection of
bacteremia and fungemia. Clin Microbiol Rev 1997;10:444-465 2. Procop GW, Cockerill FR III, Vetter
EA, et al: Performance of five agar media for recovery of fungi from isolator blood cultures. J Clin
Microbiol 2000;38(10):3827-3829
Useful For: Recovery and identification of dermatophyte fungi from hair, skin, and nail infection
specimens
Interpretation: Positive cultures are reported with organism identification. Negative reports are issued
after 30 days incubation.
Reference Values:
Negative
If positive, fungus or yeast will be identified.
Useful For: Diagnosing fungal infections from specimens other than blood, skin, hair, nail, and vagina
(separate tests are available for these specimen sites)
Interpretation: Positive cultures of yeast and filamentous fungi are reported with the organism
identification. The clinician must determine whether or not the presence of an organism is significant. A
final negative report is issued after 24 days of incubation.
Reference Values:
Negative
If positive, fungus will be identified.
Clinical References: Shea YR: General approaches for detection and identification of fungi. In
Manual of Clinical Microbiology. 10th edition. Edited by J Versalovic, KC Carroll, et al. Washington,
DC, ASM Press, 2011, pp 1776-1792
Useful For: Diagnosing fungal infections from cerebrospinal fluid (separate tests are available for other
specimen sites)
Interpretation: Positive cultures of yeast and filamentous fungi are reported with the organism
identification. The clinician must determine whether or not the presence of an organism is significant. A
final negative report is issued after 24 days of incubation.
Reference Values:
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 894
Negative
If positive, fungus will be identified.
Clinical References: Shea YR: General approaches for detection and identification of fungi. In
Manual of Clinical Microbiology. 10th edition. Edited by J Versalovic, KC Carroll, et al: Washington
DC, ASM Press, 2011, pp 1776-1792
Useful For: Monitoring therapy Managing chronic recurring disease Determining the etiology of
infectious vaginitis when other tests have been uninformative
Interpretation: Meaningful diagnosis of vaginal candidiasis requires that 1) yeast are demonstrable
in the affected area and 2) clinical symptoms and signs are consistent with the disease. Since in up to
20% of healthy women, yeast cells are part of the normal vaginal flora, the presence of Candida on
culture may be meaningless or misleading unless other clinical factors are considered.
Reference Values:
Negative
If positive, yeast will be identified.
Clinical References: 1. McCormack WM: Vulvovaginitis and cervicitis. In Principles and Practice
of Infectious Diseases. Sixth edition. Edited by GL Mandell, JE Bennett, R Dolin: Philadelphia,
Elsevier Inc, 2005, pp 1357-1372 2. Sutton DA: Specimen collection, transport, and processing:
Mycology. In Manual of Clinical Microbiology. Ninth edition. Edited by PR Murray, EJ Baron, et al:
Washington DC. ASM Press, 2007, pp 1728-1736
FS Fungal Smear
84390 Clinical Information: Many fungi in the environment cause disease in severely compromised
human hosts. Accordingly, the range of potential pathogenic fungi has increased as the number of
immunosuppressed individuals (persons with AIDS, patients receiving chemotherapy or transplant
rejection therapy, etc.) has increased. Few fungal diseases can be diagnosed clinically; most are
diagnosed by isolating and identifying the infecting fungus in the clinical laboratory.
Reference Values:
Negative
Clinical References: Lockhart SR, Diekema DJ, Pfaller MA: The epidemiology of fungal
infections. In Clinical Mycology. Edited by EJ Anaissie, MR McGinnis, MA Pfaller. Second edition.
Elsevier, Inc, 2009, pp 1-14
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the following pathogens: Candida spp., Acremonium, Aspergillus spp., Coccidioides immitis, Fusarium
spp., Histoplasma capsulatum, Trichosporon spp., Sporothrix schenckii, Saccharomyces cerevisiae, and
Pneumocystis jiroveci. The Fungitell Beta-D Glucan assay does not detect certain fungal species such as
the genus Cryptococcus, which produces very low levels of (1,3) Beta-D-glucan, nor the
Zygomycetes, such as Absidia, Mucor, and Rhizopus, which are not known to produce (1,3)
Beta-D-glucan. Studies indicate Blastomyces dermatitidis is usually not detected due to little (1,3)
Beta-D-glucan produced in the yeast phase.
Interpretation: The performance characteristics of the Fungitell assay in BAL have been determined
by Viracor-IBT Laboratories; there are no established criteria for the interpretation of Fungitell results
from BAL fluid. Research studies have evaluated the use of the Fungitell assay in BAL in both
immunocompromised patients (Mycopathologia (2013) 175:33-41) and acute eosinophilic pneumonia
(Chest (2013) 123:1302-1307).
Reference Values:
A reference range for specimens other than serum has not been established.
Interpretation: The performance characteristics of the Fungitell assay in bronchial wash have been
determined by Viracor-IBT Laboratories; there are no established criteria for the interpretation of
Fungitell results from bronchial wash fluid. Research studies have evaluated the use of the Fungitell assay
in BAL in both immunocompromised patients (Mycopathologia (2013) 175:33-41) and acute eosinophilic
pneumonia (Chest (2013) 123:1302-1307).
Reference Values:
A reference range for specimens other than serum has not been established.
Interpretation: The performance characteristics of the Fungitell assay in CSF have been determined
by Viracor-IBT Laboratories; there are no established criteria for the interpretation of Fungitell results
from CSF fluid. Research studies have evaluated the use of the Fungitell assay in CSF during a fungal
meningitis outbreak (J. Clin. Microbiol. 2013, 51(4):1285-1287).
Reference Values:
A reference range for specimens other than serum has not been established.
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FUNGS Fungitell, Serum
57874 Interpretation: Glucan values of less than 60 pg/mL are interpreted as negative. Glucan values of 60
to 79 pg/mL are interpreted as indeterminate, and suggest a possible fungal infection. Additional
sampling and testing of sera is required to interpret the results. Glucan values of greater than or equal to
80 pg/mL are interpreted as positive. Due to the potential for environmental contamination when
transferred to pour-off tubes, which can lead to false positive results, interpret positive results from
samples provided in pour-off tubes with caution. Results should be used in conjunction with clinical
findings, and should not form the sole basis for a diagnosis or treatment decision. The Fungitell test is
approved or cleared for in vitro diagnostic use by the U.S. Food and Drug Administration.
Modifications to the approved package insert have been made and the performance characteristics for
these modifications were determined by Viracor Eurofins. The Fungitell assay does not detect certain
fungal species such as the genus Cryptococcus (Tanaka et. al. 1991) which produces very low levels of
(1-3)-Beta-D-Glucan. The assay also does not detect the Zygomycetes such as Absidia, Mucor and
Rhizopus (Mitsuya et al. 1994) which are not known to produce (1-3)-Beta-D-Glucan. In addition, the
yeast phase of Blastomyces dermatitidis produces little (1-3)-Beta-D-Glucan and may not be detected
by the assay (Girouard et al. 2007).
Reference Values:
Less than 60 pg/mL
Clinical References: 1. Kwiatkowski TJ Jr, Bosco DA, LeClerc AL, et al: Mutations in the
FUS/TLS Gene on Chromosome 16 Cause Familial Amyotrophic Lateral Sclerosis. Science,
2009;323:1205-1208 2. Loy CT, McCusker E, Kril JJ, et al: Very Early-Onset Frontotemporal
Dementia with no Family History Predicts Underlying Fused In Sarcoma Pathology. Brain
2010;133:1-2 3. Munoz DG, Neumann M, Kusaka H, et al: FUS Pathology in Basophilic Inclusion
Body Disease. Acta Neuropathol 2009;118:617-627 4. Neumann M, Bentmann E, Dormann D, et al:
FET Proteins TAF15 and EWS are Selective Markers that Distinguish FTLD with FUS Pathology from
Amyotrophic Lateral Sclerosis with FUS Mutations. Brain 2011;134:2595-2609 5. Neumann M,
Rademakers R, Roeber S, et al: A New Subtype of Frontotemporal Lobar Degeneration with FUS
Pathology. Brain 2009;132:2922-2931 6. Neumann M, Roeber S, Kretzchmar HA, et al: Abundant
FUS-Immunoreactive Pathology in Neuronal Intermediate Filament Inclusion Disease. Acta
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 897
Neuropathol 2009;118:605-616 7. Urwin H, Josephs KA, Rohrer JD, et al: FUS Pathology Defines the
Majority of Tau- and TDP-43- Negative Frontotemporal Lobar Degeneration. Acta Neuropathol
2010;120:33-41
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Reference Values:
<0.35 kU/L
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 898
GABA Gabapentin, Serum
80826 Clinical Information: Gabapentin is an antiepileptic drug that is effective in treating seizures,
neuropathies, and a variety of neurological and psychological maladies. Although designed as a gamma
amino butyric acid (GABA) analogue, gabapentin does not bind to GABA receptors, nor does it affect
the neuronal uptake or degradation of GABA. In fact, the precise mechanism by which it exerts its
analgesic and anticonvulsant effects is unknown. After oral administration and absorption, gabapentin
circulates essentially unbound to serum proteins. In addition, gabapentin does not undergo hepatic
metabolism unlike most other antiepileptic drugs and is eliminated almost entirely by renal excretion
with a clearance that approximates the glomerular filtration rate. The elimination half-life is 5 to 7 hours
in patients with normal renal function. Since gabapentin does not bind to serum proteins, it does not
exhibit pharmacokinetic variability and interactions with other highly protein-bound medications (ie,
phenytoin). In addition, the lack of hepatic metabolism eliminates the interactions with other hepatically
cleared medications which can induce/inhibit hepatic drug metabolizing enzyme systems (cytochrome
P450s). Therefore, gabapentin serum concentrations are not changed following the addition or
discontinuation of other common anticonvulsants (ie, phenobarbital, phenytoin, carbamazepine, or
valproic acid), nor are their serum concentration altered upon the addition or discontinuation of
gabapentin. In general, adverse effects with gabapentin are infrequent and usually resolve with
continued treatment. The most common side effects include somnolence, dizziness, ataxia, and fatigue.
Experience to date indicated that gabapentin is safe and relatively nontoxic.
Useful For: Monitoring serum gabapentin concentrations Assessing compliance Adjusting dosage in
patients
Interpretation: Therapeutic ranges are based on specimens drawn at trough (ie, immediately before
the next dose). Most individuals display optimal response to gabapentin with serum levels of 2 to 20
mcg/mL. Some individuals may respond well outside of this range, or may display toxicity within the
therapeutic range; thus, interpretation should include clinical evaluation. Some patients require high
doses to achieve response, resulting in concentrations as high as 80 mcg/mL. Dosage reduction should
be based on signs of toxicity, not the serum concentration.
Reference Values:
2.0-20.0 mcg/mL
Units: ug/mL
Reference Values:
0-17 years: not established
> or =18 years: <0.7 mcg/24 hour
Reference Values:
<0.5 mcg/g
Clinical References: 1. Otherson JB, Maize JC, Woolson RF, Budisavljevic MN: Nephrogenic
systemic fibrosis after exposure to gadolinium in patients with renal failure. Nephrol Dial Transplant
2007;10:1093-1100 2. Perazella MA: Nephrogenic systemic fibrosis, kidney disease, and gadolinium: is
there a link? Clin J AM Soc Nephrol 2007;2:200-202 3. Saitoh T, Hayasaka K, Tanaka Y, et al:
Dialyzability of gadodiamide in hemodialysis patients. Radiat Med 2006;24:445-451 4. High WA,
Ayers RA, Cowper SE: Gadolinium is quantifiable within the tissue of patients with nephrogenic
systemic fibrosis. J Am Acad Dermatol 2007;56:710-712 5. High WA, Ayers RA, Chandler J, et al:
Gadolinium is detectable within the tissue of patients with nephrogenic systemic fibrosis. J Am Acad
Dermatol 2007;56:21-26 6. Christensen KN, Lee CU, Hanley MM, et al: Quantification of gadolinium
in fresh skin and serum samples from patients with nephrogenic systemic fibrosis. J Am Acad Dermat
2011;64(1):91-96 7. Girardi M, Kay J, Elston DM, et al: Nephrogenic systemic fibrosis:
Clinicopathological definition and workup recommendations. J Am Acad Dermatol 2011;65:1095-1106
Reference Values:
<0.5 ng/mL
Clinical References: 1. Othersen JB, Maize JC, Woolson RF, Budisavljevic MN: Nephrogenic
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 901
systemic fibrosis after exposure to gadolinium in patients with renal failure. Nephrol Dial Transplant
2007;22:3179-3185 2. Perazella MA: Nephrogenic systemic fibrosis, kidney disease, and gadolinium: is
there a link? Clin J Am Soc Nephrol 2007;2:200-202 3. Leung N, Pittelkow M, Lee CU, et al: Chelation
of gadolinium with deferoxamine in a patient with nephrogenic systemic fibrosis. NDT Plus
2009;2:309-311 4. Christensen KN, Lee CU, Hanley MM, et al: Quantification of gadolinium in fresh
skin and serum samples from patients with nephrogenic systemic fibrosis. J Am Acad Dermat
2011;64(1):91-96 5. Girardi M, Kay J, Elston DM, et al: Nephrogenic systemic fibrosis:
Clinicopathological definition and workup recommendations. J Am Acad Dermatol 2011;65:1095-1106
6. Telgmann L, Sperling M, Karst U: Determination of gadolinium-based MRI contrast agents in
biological and environmental samples: A review. Analytica Chimica Acta 2013;764:1-16
Useful For: An aid in documenting past exposure to gadolinium-containing chelates and to monitor the
effectiveness of dialysis
Interpretation: Elevated gadolinium (>0.7 mcg/g creatinine) observed in a random urine specimen
collected more than 96 hours after administration of gadolinium-containing contrast media may indicate
impaired ability to eliminate gadolinium or continued exposure, suggesting either reduced renal function
or exposure to anthropogenic sources. Patients with reduced renal function who have been exposed to
gadolinium may have an increased risk to develop nephrogenic systemic fibrosis. The normal value is less
than 0.8 mcg/g creatinine; 95% of unexposed patients will have values below 0.1 mcg/g creatinine. The
lower limit of detection is 0.1 mcg/g creatinine.
Reference Values:
0-17 years: not established
> or =18 years: <0.8 mcg/g creatinine
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 902
GATOL Galactitol, Quantitative, Urine
62440 Clinical Information: Galactosemia is an autosomal recessive disorder that results from a
deficiency of 1 of the 3 enzymes catalyzing the conversion of galactose to glucose:
galactose-1-phosphate uridyltransferase (GALT), galactokinase (GALK), and uridine diphosphate
galactose-4-epimerase (GALE). GALT deficiency is the most common cause of galactosemia and is
often referred to as classic galactosemia. The complete or near complete deficiency of the GALT
enzyme is life threatening. If left untreated, complications include liver failure, sepsis, cognitive and
intellectual disabilities, and death. Galactosemia is treated with a galactose-free diet, which allows for
rapid recovery from the acute symptoms and a generally good prognosis. Despite adequate treatment
from an early age, children with galactosemia remain at increased risk for developmental delays, speech
problems, abnormalities of motor function, and females are at increased risk for premature ovarian
failure. Based upon reports by newborn screening programs, the frequency of classic galactosemia in
the United States is approximately 1 in 30,000. Galactose levels may be continuously elevated in
individuals affected with galactosemia even with a galactose-restricted diet regimen due to an
endogenous production of galactose. The reduction of galactose to galactitol is an alternate pathway of
galactose disposition when galactose metabolism is impaired. The excretion of abnormal quantities of
galactitol in the urine of patients is characteristic of this disorder, and patients may have abnormal levels
of galactitol even with dietary compliance. Daily consumption of galactose may cause urine levels to
rise thus providing information on effectiveness of or compliance with treatment, but unlike erythrocyte
galactose-1-phosphate (GAL1P) and plasma galactose, urine galactitol levels usually do not provide
insight into acute and transient effects of galactose intake.
Interpretation: The concentration of galactitol is provided along with reference ranges for patients
with galactosemia and normal controls.
Reference Values:
0-11 months: <109 mmol/mol creatinine
1-3 years: <52 mmol/mol creatinine
417 years: <16 mmol/mol creatinine
> or =18 years: <13 mmol/mol creatinine
Clinical References: 1. Online Mendelian Inheritance in Man. 230400, 230200, and 230350,
respectively. National Center for Biotechnology Information. Available at
www.ncbi.nlm.nih.gov/Omim 2. Berry GT: Classic Galactosemia and Clinical Variant Galactosemia. In
GeneReviews, Edited by RA Pagon, MP Adam, HH Ardinger, et al. University of Washington, Seattle;
1993-2015. 2000 Feb 4 (Updated 2014 Apr 3). Available at:
http://www.ncbi.nlm.nih.gov/books/NBK1518/ 3. Holton JB, Walter JH, Tyfield LA: Galactosemia. In
The Metabolic and Molecular Basis of Inherited Disease. Vol 1. Eighth edition. Edited by CR Scriver,
AL Beadut. New York, McGraw-Hill Book Company, 2001, pp 1553-1587
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 904
The upper limit of normal may change with the specific activity of the substrate. Elevated values have no
known clinical significance.
Reference Values:
> or =1.20 nmol/h/mg protein
Useful For: Diagnosis of galactokinase deficiency, the second most common cause of galactosemia
Interpretation: An interpretive report will be provided. See Galactosemia Testing Algorithm in
Special Instructions for additional information. For galactose-1-phosphate uridyltransferase deficiency,
see GALT / Galactose-1-Phosphate Uridyltransferase, Blood. For epimerase deficiency, see GALE /
UDP-galactose 4 epimerase (GALE), Blood.
Reference Values:
> or =0.7 nmol/h/mg of hemoglobin
Clinical References: 1. Li, Y, Ptolemy AS, Harmonay L, et al: Ultra fast and sensitive liquid
chromatography tandem mass spectrometry based assay for galactose-1-phosphate uridylyltransferase
and galactokinase deficiencies. Mol Gen Metab 2011;102(1):33-40 2. Ko DH, Jun SH, Park HD, et al:
Multiplex enzyme assay for galactosemia using ultraperformance liquid chromatography-tandem mass
spectrometry. Clin Chem 2010;56:764-771 3. Hennermann JB, Schadewaldt P, Vetter B, et al: Features
and outcome of galactokinase deficiency in children diagnosed by newborn screening. J Inherit Metab
Dis 2011;34:399-407 4. Walter JH, Fridovich-Keil JL: Galactosemia. In The Online Metabolic and
Molecular Bases of Inherited Disease. Edited by D Valle, AL Beaudet, B Vogelstein, et al.
McGraw-Hill, New York, 2014, Accessed January 26, 2016. Available at:
http://ommbid.mhmedical.com/content.aspx?bookid=971&Sectionid=62672411
Reference Values:
1-7 days: <5.4 mg/dL
8-14 days: <3.6 mg/dL
>14 days: <2.0 mg/dL
Clinical References: 1. Berry GT: Classic Galactosemia and Clinical Variant Galactosemia. In
GeneReviews. Edited by RA Pagon, MP Adam, HH Ardinger, et al. Available from URL
http://www.ncbi.nlm.nih.gov/books/NBK1518/. Retrieved 03/11/2015 2. Walter JH, Fridovich-Keil JL:
Galactosemia. In The Metabolic and Molecular Bases of Inherited Disease. Edited by Valle D, Beaudet
AL, Vogelstein B, et al. New York, McGraw-Hill, 2014. Accessed January 26, 2016. Available at
http://ommbid.mhmedical.com/content.aspx?bookid=971&Sectionid=62672411
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 906
prognosis. Despite adequate treatment from an early age, individuals with galactosemia remain at
increased risk for developmental delays, speech problems, and abnormalities of motor function. Females
with galactosemia are at increased risk for premature ovarian failure. Based upon reports by newborn
screening programs, the frequency of classic galactosemia in the United States is approximately 1 in
30,000, although literature reports range from 1 in 10,000 to 1 in 60,000 live births. A comparison of
plasma and urine galactose and blood galactose-1-phosphate (Gal-1-P) levels may be useful in
distinguishing among the 3 forms of galactosemia; however, these are only general patterns and further
confirmatory testing would be required to make a diagnosis. Deficiency Galactose (Plasma/Urine)
Gal-1-P (Blood) GALK Elevated Normal GALT Elevated Elevated GALE Normal-Elevated Elevated For
more information regarding diagnostic strategy, refer to Galactosemia: Current Testing Strategy and Aids
for Test Selection, Mayo Medical Laboratories Communique 2005 May;30(5). See Galactosemia Testing
Algorithm in Special Instructions for additional information.
Reference Values:
<30 mg/dL
Clinical References: 1. Berry GT: Classic Galactosemia and Clinical Variant Galactosemia. In
GeneReviews. Edited by RA Pagon, MP Adam, HH Ardinger, et al. Available at:
http://www.ncbi.nlm.nih.gov/books/NBK1518/. Retrieved 03/11/2015 2. Walter JH, Fridovich-Keil JL:
Galactosemia. In The Metabolic and Molecular Bases of Inherited Disease. Edited by Valle D, Beaudet
AL, Vogelstein B, et al. New York, McGraw-Hill, 2014. Accessed January 26, 2016. Available at:
http://ommbid.mhmedical.com/content.aspx?bookid=971&Sectionid=62672411
Useful For: Monitoring dietary therapy of patients with galactosemia due to deficiency of
galactose-1-phosphate uridyltransferase or uridine diphosphate galactose-4-epimerase
Reference Values:
Non-galactosemic: 5-49 mcg/g of hemoglobin (<1 mg/dL)
Galactosemic on galactose restricted diet: 80-125 mcg/g of hemoglobin (1-4 mg/dL)
Galactosemic on unrestricted diet: >125 mcg/g of hemoglobin (>4 mg/dL)
Clinical References: 1. Berry GT: Classic Galactosemia and Clinical Variant Galactosemia. In
GeneReviews. Edited by RA Pagon, MP Adam, HH Ardinger, et al. Available from URL
http://www.ncbi.nlm.nih.gov/books/NBK1518/. Retrieved 03/11/2015 2. Walter JH, Fridovich-Keil JL:
Chapter 72: Galactosemia. In The Metabolic and Molecular Bases of Inherited Disease. Eighth edition.
Edited by D Valle. AL Beaudet, B Vogelstein. New York, McGraw-Hill Book Company. Accessed
03/11/2015. Available at: http:// www.ommbid.com
Reference Values:
> or =24.5 nmol/h/mg of hemoglobin
Clinical References: 1. Berry GT: Classic Galactosemia and Clinical Variant Galactosemia. In
GeneReviews. Edited by RA Pagon, MP Adam, HH Ardinger, et al. Retrieved 03/11/2015. Available at:
http://www.ncbi.nlm.nih.gov/books/NBK1518/ 2. Walter JH, Fridovich-Keil JL: Galactosemia. In The
Metabolic and Molecular Bases of Inherited Disease. Edited by Valle D, Beaudet AL, Vogelstein B, et
al. New York, McGraw-Hill, 2014. Accessed January 26, 2016. Available at
http://ommbid.mhmedical.com/content.aspx?bookid=971&Sectionid=62672411
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 909
low galactose diet during infancy. The LA variant, which consists of N314D and a second mutation,
L218L, is associated with higher levels of GALT enzyme activity than the Duarte-variant allele. In
general, molecular genetic analysis with a panel of common mutations is typically performed to
determine the specific genotype. If the enzymatic and molecular results are incongruent, biochemical
phenotyping and/or molecular sequence analysis may be beneficial to help clarify results to determine a
treatment strategy and recurrence risks. For more information regarding diagnostic strategy, refer to
Galactosemia: Current Testing Strategy and Aids for Test Selection, Mayo Medical Laboratories
Communique 2005 May;30(5). See Galactosemia Testing Algorithm in Special Instructions for
additional information.
Useful For: Determining the biochemical phenotype for galactosemia when enzymatic and molecular
results are incongruent A quantitative galactose-1-phosphate uridyltransferase level (GALT /
Galactose-1-Phosphate Uridyltransferase [GALT], Blood) is required for accurate interpretation.
Reference Values:
Descriptive report
Clinical References: 1. Berry GT. Classic Galactosemia and Clinical Variant Galactosemia. In
GeneReviews. Edited by Pagon RA, Adam MP, Ardinger HH, et al. Available at
http://www.ncbi.nlm.nih.gov/books/NBK1518/. Retrieved 03/11/2015 2. Walter JH, Fridovich-Keil JL:
Galactosemia. In The Metabolic and Molecular Bases of Inherited Disease. Edited by Valle D, Beaudet
AL, Vogelstein B, et al. New York, McGraw-Hill, 2014. Accessed January 26, 2016. Available at
http://ommbid.mhmedical.com/content.aspx?bookid=971&Sectionid=62672411
Previous reports (JACI 2009; 123:426-433) have demonstrated that patients with IgE antibodies to
galactose-a-1,3-galactose are at risk for delayed anaphylaxis, angioedema, or urticaria following
consumption of beef, pork, or lamb.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 910
state to state. The diagnosis of galactosemia is established by follow-up quantitative measurement of
GALT enzyme activity. If enzyme levels are indicative of carrier or affected status, molecular testing for
common GALT mutations may be performed. If 1 or both disease-causing mutations are not detected by
targeted mutation analysis and biochemical testing has confirmed the diagnosis of galactosemia,
sequencing of the GALT gene is available to identify private mutations. The GALT gene maps to 9p13.
Several disease-causing mutations are common in patients with classic galactosemia (G/G genotype). The
most frequently observed is the Q188R classic mutation. This mutation accounts for 60% to 70% of
classical galactosemia alleles. The S135L mutation is the most frequently observed mutation in African
Americans and accounts for approximately 50% of the mutant alleles in this population. The K285N
mutation is common in those of eastern European descent and accounts for 25% to 40% of the alleles in
this population. The L195P mutation is observed in 5% to 7% of classical galactosemia. The 5 kb deletion
is common in individuals of Ashkenazi Jewish descent. The Duarte mutation (N314D and
-119_-116delGTCA) is observed in 5% of the general United States population. The rest of the mutations
detected by this method (ie, D98N, S135L, T138M, M142K, F171S, Y209C, and Q344K) are all
uncommon, but known to be recurrent in the general population. These mutations, in addition to the LA
variant, are included in GAL14 / Galactosemia Gene Analysis (14-Mutation Panel) and in GCT /
Galactosemia Reflex, Blood. See Galactosemia Testing Algorithm in Special Instructions for additional
information. Refer to Galactosemia: Current Testing Strategy and Aids for Test Selection, Mayo Medical
Laboratories Communique 2005 May;30(5) for more information regarding diagnostic strategy.
Useful For: Second-tier test for confirming a diagnosis of galactosemia (indicated by enzymatic
testing or newborn screening) Carrier testing family members of an affected individual of known
genotype (has mutations included in the panel) Resolution of Duarte variant and Los Angeles (LA)
variant genotypes
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Elsas LJ 2nd, Lai K: The molecular biology of galactosemia. Genet Med
1998 Nov-Dec;1(1):40-48 2. Kaye CI, Committee on Genetics, Accurso F, et al: Newborn screening
fact sheets. Pediatrics 2006 Sep;118(3):e934-963 3. Novelli G, Reichardt JK: Molecular basis of
disorders of human galactose metabolism: past, present, and future. Mol Genet Metab 2000
Sep-Oct;71(1-2):62-65
Useful For: Preferred test for diagnosis, carrier detection, and determination of genotype of
galactose-1-phosphate uridyltransferase deficiency, the most common cause of galactosemia
Differentiating Duarte variant galactosemia from classic galactosemia Confirming results of newborn
screening programs
Reference Values:
> or =24.5 nmol/h/mg of hemoglobin
Clinical References: 1. Berry GT: Classic Galactosemia and Clinical Variant Galactosemia. In
GeneReviews. Edited by RA Pagon, MP Adam, HH Ardinger, et al. Retrieved 03/11/2015. Available at
www.ncbi.nlm.nih.gov/books/NBK1518/ 2. Walter JH, Fridovich-Keil JL: Chapter 72: Galactosemia. In
The Metabolic and Molecular Bases of Inherited Disease. Eighth edition. Edited by D Valle. AL Beaudet,
B Vogelstein. New York, McGraw-Hill Book Company. Accessed 03/11/2015. Available at
www.ommbid.com
Useful For: An aid in distinguishing normal/benign thyroid gland from thyroid carcinoma
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 912
Interpretation: This test includes only technical performance of the stain (no pathologist
interpretation is performed). If diagnostic consultation by a pathologist is required order 70012 /
Pathology Consultation. The positive and negative controls are verified as showing appropriate
immunoreactivity. If a control tissue is not included on the slide, a scanned image of the relevant quality
control tissue is available upon request. Please contact 1-855-516-8404. Interpretation of this test should
be performed in the context of the patient's clinical history and other diagnostic tests by a qualified
pathologist.
Useful For: An aid in prognosis for patients diagnosed with heart failure Risk-stratification of heart
failure patients An early indication of treatment failure and as a therapeutic target
Reference Values:
<24 months: not established
2-17 years: < or =25.0 ng/mL
> or =18 years: < or =22.1 ng/mL
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 913
Clinical References: 1. Weintraub NL, Collins SP, Pang PS, et al: Acute heart failure syndromes:
emergency department presentation, treatment, and disposition: current approaches and future aims: a
scientific statement from the American Heart Association. Circulation 2010;122:1975-1996 2. Felker GM,
Fiuzat M, Shaw LK, et al: Galectin-3 in ambulatory patients with heart failure: results from the
HF-ACTION Study. Circ Heart Fail 2012 Jan;5(1):72-78 3. Lok DJ, Van Der Meer P, de la Porte PW, et
al: Prognostic value of galectin-3, a novel marker of fibrosis, in patients with chronic heart failure: data
from the DEAL-HF study. Clin Res Cardiol 2010 May;99(5):323-328 4. de Boer RA, Lok DJ, Jaarsma T,
et al: Predictive value of plasma galectin-3 levels in heart failure with reduced and preserved ejection
fraction. Ann Med 2011 Feb;43(1):60-68 5. Christenson RH, Duh SH, Wu AH, et al: Multi-center
determination of galectin-3 assay performance characteristics: Anatomy of a novel assay for use in heart
failure. Clin Biochem 2010 May;43(7-8):683-690 6. Meeusen JW, Johnson JN, Gray A, et al: Soluble
ST2 and galectin-3 in pediatric patients without heart failure. Clin Biochem 2015;Dec;48(18):1337-1340
Useful For: Identifying mutations in individuals who test negative for the common mutations and who
have a biochemical diagnosis of galactosemia or galactose-1-phosphate uridyltransferase activity levels
indicative of carrier status
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 914
Interpretation: All detected alterations will be evaluated according to the American College of
Medical Genetics and Genomics (AMCG) recommendations.(1) Variants will be classified based on
known, predicted, or possible pathogenicity and reported with interpretive comments detailing their
potential or known significance.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for
standards for interpretation and reporting of sequence variations: Revisions 2007. Genet Med
2008;10(4):294-300 2. Elsas LJ 2nd, Lai K: The molecular biology of galactosemia. Genet Med 1998
Nov-Dec;1(1):40-48 3. Novelli G, Reichardt JK: Molecular basis of disorders of human galactose
metabolism: past, present, and future. Mol Genet Metab 2000 Sep-Oct;71(1-2):62-65 4. Bosch AM, Ijlst
L, Oostheim W, et al: Identification of novel mutations in classical galactosemia. Hum Mutat 2005
May;25(5):502
Useful For: An adjunct in the interpretation of hemoglobin electrophoresis results Evaluation for
suspected gamma variants or nondeletional hereditary persistence of fetal hemoglobin (HPFH) Assess
for unstable gamma chain variants (there are occasionally newborns who are jaundiced at birth, often
requiring phototherapy, in which all other tests for causes of hemolysis are unrevealing)
Interpretation: An interpretive report will be provided and will include specimen information, assay
information, and whether the specimen was positive for any mutations in the gene. If positive, the
mutation will be correlated with clinical significance, if known.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Crowley MA, Mollan TL, Abdulmalik OY, et al: A hemoglobin variant
associated with neonatal cyanosis and anemia. N Engl J Med 2011;364:1837-1843 2. Cui J, Baysdorfer
C, Azimi M, et al: Identification of three novel Hb F variants: Hb F-Hayward [G(NA1)Gly->Asp,
GGT>GAT], Hb F-Chori-I [AT16(A13)Gly->Asp, GGC>GAC] and Hb F-Chori-II
[AI29(B11)Gly->Glu, GGA>GAA]. Hemoglobin 2012;36:305-309 3. Akinsheye I, Alsultan A,
Solovieff N, et al: Fetal hemoglobin in sickle cell anemia. Blood 2011;118:19-27 4. Disorders of
Hemoglobin Genetics, Pathophysiology, and Clinical Management. Second edition. Edited by M
Steinberg, B Forget, D Higgs, D Weatherall. New York, Cambridge University Press, 2009 5.
Molecular Hematology. Third edition. Edited by D Provan, J Gribben. Malden, Massachusets,
Blackwell Publishing, 2010 6. Color Atlas of Hemoglobin Disorders: A Compendium Based on
Proficiency Testing. Edited by JD Hoyer, SH Kroft. Northfield, IL. College of American Pathologists,
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 915
2003 7. Merchant S, Oliveira JL, Hoyer JD, Viswanatha DS: Chapter 24. Molecular diagnosis in
hematopathology. In Hematopathology: A Volume in the Series: Foundations in Diagnostic Pathology.
Second edition. Edited by J Goldblum. E Hsi. Churchill Livingstone. 2012
Useful For: Diagnosing and monitoring hepatobiliary disease, it is currently the most sensitive
enzymatic indicator of liver disease Ascertaining whether observed elevations of alkaline phosphatase are
due to skeletal disease (normal gamma-glutamyltransferase: GGT) or reflect the presence of hepatobiliary
disease (elevated GGT) A screening test for occult alcoholism
Reference Values:
Males
1-6 years: 7-19 U/L
7-9 years: 9-22 U/L
10-13 years: 9-24 U/L
14-15 years: 9-26 U/L
16-17 years: 9-27 U/L
18-35 years: 9-31 U/L
36-40 years: 8-35 U/L
41-45 years: 9-37 U/L
46-50 years: 10-39 U/L
51-54 years: 10-42 U/L
55 years: 11-45 U/L
> or =56 years: 12-48 U/L
Reference values have not been established for patients <12 months of age.
Females
>1 year: 6-29 U/L
Reference values have not been established for patients <12 months of age.
Reference Values:
Trough: 1.0-3.0 mcg/mL
Peak: 3.0-12.5 mcg/mL
Clinical References: 1. Perrottet N, Decosterd LA, Meylan P, et al: Valganciclovir in adult solid
organ transplant recipients: pharmacokinetic and pharmacodynamic characteristics and clinical
interpretation of plasma concentration measurements. Clin Pharmacokinet 2009;48(6):399-418 2. Uges
D: Therapeutic and toxic drug concentrations. In The International Association of Forensic
Toxicologists. 2009 Dec. Available from URL: www.tiaft.org
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syndrome. Anti-GQ1b antibodies are seen in more than 80 percent of patients with Miller-Fisher
syndrome and may be elevated in GBS patients with ophthalmoplegia. The role of isolated anti-GM2
antibodies is unknown. These tests by themselves are not diagnostic and should be used in conjunction
with other clinical parameters to confirm disease.
Reference Values:
29 IV or less: Negative
30 50 IV: Equivocal
51 100 IV: Positive
101 IV or greater: Strong Positive
Useful For: Supporting diagnosis of neurological diseases-primarily motor neuron disease and motor
neuropathies
Interpretation: High titers (>1:2,000) have been found only in patients with multifocal motor
neuropathy and not with motor neuron disease. About 30% to 50% of patients with these clinical
syndromes or the pure motor variant of chronic inflammatory demyelinating polyneuropathy have
increased antibody titers. Increased antibody titers, therefore, appear to be a specific but not sensitive
marker of those related disorders. Borderline elevation of titers against ganglioside epitopes may be seen
in patients with motor neuron disease or motor neuropathy For IgG and IgM antibodies directed against
monosialo GM1 and disialo GD1b, 99% of 182 age- and sex-stratified normal individuals had titers
<1:1,000; 99% of 121 patients with well-defined motor neuron disease had titers <1:2,000; and all
patients with titers >1:2,000 had motor neuropathy.
Reference Values:
IgG monosialo GM1 1:500
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IgM monosialo GM1 =1:2,000
Clinical References: 1. Taylor BV, Gross L, Windebank AJ: The sensitivity and specificity of
anti-GM1 antibody testing. Neurology 1996;47:951-955 2. Vernino S,Wolfe GI: Antibody testing in
peripheral neuropathies. Neurol Clin 2007;25:29-46 3. Kaida K, Ariga T, Yu RK: Antiganglioside
antibodies and their pathophysiological effects on Guillain-Barre syndrome and related disorders-a
review. Glycobiology 2009;19:676-692
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical
utility of food-specific IgG tests has not been established. These tests can be used in special clinical
situations to select foods for evaluation by diet elimination and challenge in patients who have
food-related complaints. It should be recognized that the presence of food-specific IgG alone cannot be
taken as evidence of food allergy and only indicates immunologic sensitization by the food allergen in
question. This test should only be ordered by physicians who recognize the limitations of the test.
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: An aid in the characterization of islet cell tumors and endocrine tumors of the
gastrointestinal tract
Interpretation: This test includes only technical performance of the stain (no pathologist interpretation
is performed). If diagnostic consultation by a pathologist is required order 70012 / Pathology
Consultation. The positive and negative controls are verified as showing appropriate immunoreactivity. If
a control tissue is not included on the slide, a scanned image of the relevant quality control tissue is
available upon request. Please contact 1-855-516-8404. Interpretation of this test should be performed in
the context of the patient's clinical history and other diagnostic tests by a qualified pathologist.
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GAST Gastrin, Serum
8512 Clinical Information: Gastrin is a peptide hormone produced by mucosal G cells of the gastric
antrum. It is synthesized as preprogastrin, cleaved to progastrin, which undergoes several
posttranslational modifications, in particular sulfation, and is finally processed into the mature 34-amino
acid, gastrin-34. Gastrin-34 may be cleaved further into the shorter 17-amino acid, gastrin-17. Either
may be secreted as a c-terminal amidated or unamidated isoform. A number of additional, smaller
gastrin fragments, as well as gastrin molecules with atypical posttranslational modifications (eg, absent
sulfation), may also be secreted in small quantities. Gastrin half-life is short, 5 minutes for amidated
gastrin-17, and 20 to 25 minutes for amidated gastrin-34. Elimination occurs through peptidase cleavage
and renal excretion. Gastrin-17 I (nonsulfated form) and gastrin-17 II (sulfated) appear equipotent.
Their biological effects are chiefly associated with the amidated isoforms and consist of promotion of
gastric epithelial cell proliferation and differentiation to acid-secreting cells, direct promotion of acid
secretion, and indirect stimulation of acid production through histamine release. In addition, gastrin
stimulates gastric motility and release of pepsin and intrinsic factor. Most gastrin isoforms with atypical
posttranslational modifications and most small gastrin fragments display reduced or absent bioactivity.
This assay measures predominately gastrin-17. Larger precursors and smaller fragments have little or no
cross-reactivity in the assay. Intraluminal stomach pH is the main factor regulating gastrin production
and secretion. Rising gastric pH levels result in increasing serum gastrin levels, while falling pH levels
are associated with mounting somatostatin production in gastric D cells. Somatostatin, in turn,
downregulates gastrin synthesis and release. Other, weaker factors that stimulate gastrin secretion are
gastric distention, protein-rich foods, and elevated secretin or serum calcium levels. Serum gastrin
levels may also be elevated in gastric distention due to gastric outlet obstruction, and in a variety of
conditions that lead to real or functional gastric hypo- or achlorhydria (gastrin is secreted in an
attempted compensatory response to achlorhydria). These include atrophic gastritis with or without
pernicious anemia; a disorder characterized by destruction of acid-secreting (parietal) cells of the
stomach, gastric dumping syndrome, and surgically excluded gastric antrum. In atrophic gastritis, the
chronic cell-proliferative stimulus of the secondary hypergastrinemia may contribute to the increased
gastric cancer risk observed in this condition. Gastrin levels are pathologically increased in gastrinoma,
a type of neuroendocrine tumor that can occur in the pancreas (20%-40%) or in the duodenum
(50%-70%). The triad of nonbeta islet cell tumor of the pancreas (gastrinoma), hypergastrinemia, and
severe ulcer disease is referred to as the Zollinger-Ellison syndrome. Over 50% of gastrinomas are
malignant and can metastasize to regional lymph nodes and the liver. About 25% of gastrinomas occur
as part of the multiple endocrine neoplasia type 1 (MEN 1) syndrome and are associated with
hyperparathyroidism and pituitary adenomas. These MEN 1-associated tumors have been observed to
occur at an earlier age than sporadic tumors and often follow a more benign course.
Useful For: Investigation of patients with achlorhydria or pernicious anemia Investigation of patients
suspected of having Zollinger-Ellison syndrome Diagnosis of gastrinoma; basal and secretin-stimulated
serum gastrin measurements are the best laboratory tests for gastrinoma
Interpretation: Achlorhydria is the most common cause of elevated serum gastrin levels. The most
common cause for achlorhydria is treatment of gastroduodenal ulcers, nonulcer dyspepsia, or
gastroesophageal reflux with proton pump inhibitors (substituted benzimidazoles, eg, omeprazole).
Other causes of hypo- and achlorhydria include chronic atrophic gastritis with or without pernicious
anemia, gastric ulcer, gastric carcinoma, and previous surgical or traumatic vagotomy. If serum B12
levels are significantly low (<150 ng/L), even if the intrinsic factor blocking antibody tests are negative,
a serum gastrin level above the reference range makes it likely the patient is nonetheless suffering from
pernicious anemia. Hypergastrinemia with normal or increased gastric acid secretion is suspicious of a
gastrinoma (Zollinger-Ellison syndrome). Gastrin levels <100 pg/mL are observed so uncommonly in
untreated gastrinoma patients with intact upper gastrointestinal anatomy as to virtually exclude the
diagnosis. The majority (>60%) of patients with gastrinoma have very significantly elevated serum
gastrin levels (>400 pg/mL). Levels of >1,000 pg/mL in a gastric- or duodenal-ulcer patient without
previous gastric surgery, on no drugs, who has a basal gastric acid output of >15 mmol/hour (>5
mmol/hour in patients with prior acid-reducing surgery) are considered diagnostic of gastrinoma. If
there are any doubts about gastric acid output, an infusion of 0.1 N HCl into the stomach reduces the
serum gastrin in patients with achlorhydria, but not in those with gastrinoma. Other conditions that may
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be associated with hypergastrinemia in the face of normal or increased gastric acid secretion include
gastric and, rarely, duodenal ulcers, gastric outlet obstruction, bypassed gastric antrum, and gastric
dumping. Occasionally, diabetes mellitus, autonomic neuropathy with gastroparesis,
pheochromocytoma, rheumatoid arthritis, thyrotoxicosis, and paraneoplastic syndromes can also result
in hypergastrinemia with normal acid secretion. None of these conditions tends to be associated with
fasting serum gastrin levels >400 pg/mL, and levels >1,000 pg/mL are virtually never observed. Several
provocative tests can be used to distinguish these patients from individuals with gastrinomas. Patients
with gastrinoma, who have normal or only mildly to modestly increased fasting serum gastrin levels,
respond with exaggerated serum gastrin increases to intravenous infusions of secretin or calcium.
Because of its greater safety, secretin infusion is preferred. The best validated protocol calls for a
baseline fasting gastrin measurement, followed by an injection of 2 clinical units of secretin per kg body
weight (0.4 microgram/kg) over 1 minute and further serum gastrin specimens at 5-, 10-, 15-, 20-, and
30-minutes postinjection. A peak-gastrin increase of >200 pg/mL above the baseline value has >85%
sensitivity and near 100% specificity for gastrinoma. Secretin or calcium infusion tests are not carried
out in the clinical laboratory, but are usually performed at gastroenterology or endocrine testing units
under the supervision of a physician. They are progressively being replaced (or supplemented) by
imaging procedures, particularly duodenal and pancreatic endoscopic ultrasound. All patients with
confirmed gastrinoma should be evaluated for possible multiple endocrine neoplasia type 1 (MEN 1),
which is the underlying cause in approximately 25% of cases. If clinical, biochemical, or genetic testing
confirms MEN 1, other family members need to be screened.
Reference Values:
<100 pg/mL
There is no evidence that fasting serum gastrin levels differ between adults and children. Although
8-hour fasts are difficult or impossible to enforce in small children, serum gastrin levels after shorter
fasting periods (3-8 hours) may be 50% to 60% higher than the 8-hour fasting value.
Clinical References: 1. Ellison EC, Johnson JA: The Zollinger-Ellison syndrome: a comprehensive
review of historical, scientific, and clinical considerations. Curr Probl Surg. 2009;46:13-106 2. McColl
KE, Gillen D, El-Omar E: The role of gastrin in ulcer pathogenesis. Ballieres Best Pract Res Clin
Gastroenterol 2000;14:13-26 3. Dockray GJ, Varro A, Dimaline R, Wang T: The gastrins: their
production and biological activities. Ann Rev Phys 2001;63:119-139 4. Brandi ML, Gagel R, Angeli A, et
al: Consensus: guidelines for the diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol
Metab 2001;86:5658-5671 5. Ward PC: Modern approaches to the investigation of vitamin B12
deficiency. Clin Lab Med 2002;22:435-445
Useful For: Rapid detection of gastrointestinal infections caused by: -Campylobacter species
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(Campylobacter jejuni/Campylobacter coli/Campylobacter upsaliensis) -Clostridium difficile toxin A/B
-Plesiomonas shigelloides -Salmonella species -Vibrio species (Vibrio parahaemolyticus, Vibrio
vulnificus, Vibrio cholerae) -Vibrio cholerae -Yersinia species -Enteroaggregative Escherichia coli
(EAEC) -Enteropathogenic E coli (EPEC) -Enterotoxigenic E coli (ETEC) -Shiga toxin -E coli O157
-Shigella/Enteroinvasive E coli (EIEC) -Cryptosporidium species -Cyclospora cayetanensis -Entamoeba
histolytica -Giardia -Adenovirus F 40/41 -Astrovirus -Norovirus GI/GII -Rotavirus A -Sapovirus
Interpretation: A negative result should not rule-out infection in patients with a high pretest
probability for gastrointestinal infection. The assay does not test for all potential infectious agents of
diarrheal disease. Positive results do not distinguish between a viable/replicating organism and the
presence of a nonviable organism or nucleic acid, nor do they exclude the potential for coinfection by
organisms not contained within the panel. Results of the panel are intended to aid in the diagnosis of
illness and are meant to be used in conjunction with other clinical and epidemiological findings.
Reference Values:
Negative (for all targets)
Clinical References: 1. Centers for Disease Control and Prevention. Incidence and Trends of
Infection with Pathogens Transmitted Commonly Through Food-Foodborne Diseases Active
Surveillance Network, 10 U.S. Sites, 1996-2012. MMWR Morb Mortal Wkly Rep 2013;62(15):283-287
2. Khare R, Espy MJ, Cebelinski E, et al: Comparative evaluation of two commercial multiplex panels
for detection of gastrointestinal pathogens by use of clinical stool specimens. J Clin Microbiol 2014
Oct;52(10):3667-3673 3. Centers for Disease Control and Prevention. Summary of Notifiable
Diseases-United States, 2012. MMWR Morb Mortal Wkly Rep 2014;61(53):1-121 4. DuPont HL:
Persistent Diarrhea: A Clinical Review. JAMA 2016;315(24):2712-2723 doi:10.1001/jama.2016.7833
Useful For: Characterizing carcinomas, including primary bladder and breast carcinomas, and some
types of mesenchymal and neuroectodermal tumors
Interpretation: This test includes only technical performance of the stain (no pathologist
interpretation is performed). If diagnostic consultation by a pathologist is required, order 70012 /
Pathology Consultation. The positive and negative controls are verified as showing appropriate
immunoreactivity. If a control tissue is not included on the slide, a scanned image of the relevant quality
control tissue is available upon request; contact 855-516-8404. Interpretation of this test should be
performed in the context of the patient's clinical history and other diagnostic tests by a qualified
pathologist.
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GBAZ Gaucher Disease, Full Gene Analysis
35438 Clinical Information: Gaucher disease is a relatively rare lysosomal storage disorder resulting from a
deficiency of acid beta-glucocerebrosidase. Reduced or absent activity of this enzyme results in
accumulation of its substrate in lysosomes, interfering with cell function. There are 3 major types of
Gaucher disease: nonneuropathic (type 1), acute neuropathic (type 2), and subacute neuropathic (type 3).
In addition, there are 2 rare presentations of Gaucher disease: a perinatal lethal form associated with skin
abnormalities and nonimmune hydrops fetalis, and a cardiovascular form presenting with calcification of
the aortic and mitral valves, mild splenomegaly, and corneal opacities. Gaucher disease demonstrates
large clinical variability, even within families. Type 1 accounts for over 95% of all cases of Gaucher
disease and is the presentation commonly found among Ashkenazi Jewish patients. The carrier rate of
Gaucher disease in the Ashkenazi Jewish population is 1:18. There is a broad spectrum of disease in type
1 Gaucher disease, with some patients exhibiting severe symptoms and others very mild disease. Type 1
disease does not involve nervous system dysfunction; patients may display anemia, low blood platelet
levels, massively enlarged livers and spleens, lung infiltration, and extensive skeletal disease. Type 2 is
characterized by early-onset neurologic disease with rapid progression to death by 2 to 4 years of age.
Type 3 may have early onset of symptoms, but generally a slower disease progression than type 2.
Mutations in the GBA gene cause the clinical manifestations of Gaucher disease. Over 250 mutations
have been reported to date. The N370S and L444P mutations have the highest prevalence in most
populations. N370S is associated with type 1 Gaucher disease, and individuals with at least 1 copy of this
mutation do not develop the primary neurologic disease seen in types 2 and 3. Conversely, L444P is
associated with neurologic disease. For carrier screening of the general population, the recommended test
is GAUP / Gaucher Disease, Mutation Analysis, GBA, which tests for the 8 most common GBA
mutations. For diagnostic testing (ie, potentially affected individuals), enzyme testing (BGL /
Beta-Glucosidase, Leukocytes) should be performed prior to mutation analysis. In individuals with
abnormal enzyme activity and 1 or no mutations detected by a panel of common mutations, sequence
analysis of the GBA gene should be utilized to detect private mutations.
Useful For: Confirmation of a diagnosis of Gaucher disease Carrier screening in cases where there is a
family history of Gaucher disease, but an affected individual is not available for testing or disease-causing
mutations have not been identified
Interpretation: All detected alterations are evaluated according to American College of Medical
Genetics recommendations.(1) Variants are classified based on known, predicted, or possible
pathogenicity and reported with interpretive comments detailing their potential or known significance.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for
standards of interpretation and reporting of sequence variations: revisions 2007. Genet Med
2008;10(4):294-300 2. Guggenbuhl P, Grosbois B, Chales G: Gaucher disease. Joint Bone Spine
2008;75(2):116-124 3. Hruska KS, LaMarca ME, Scott CR, et al: Gaucher disease: mutation and
polymorphism spectrum in the glucocerebrosidase gene (GBA). Hum Mutat 2008;29(5):567-583
Useful For: Confirmation of a suspected clinical diagnosis of Gaucher disease Carrier testing for
individuals of Ashkenazi Jewish ancestry or who have a family history of Gaucher disease Prenatal
diagnosis of Gaucher disease in at-risk pregnancies
Useful For: An aid in the identification of extramammary Paget's disease, carcinomas of the salivary
glands, sweat glands, and prostate
Interpretation: This test includes only technical performance of the stain (no pathologist
interpretation is performed). If diagnostic consultation by a pathologist is required order 70012 /
Pathology Consultation. The positive and negative controls are verified as showing appropriate
immunoreactivity. If a control tissue is not included on the slide, a scanned image of the relevant quality
control tissue is available upon request. Please contact 1-855-516-8404. Interpretation of this test should
be performed in the context of the patient's clinical history and other diagnostic tests by a qualified
pathologist.
Reference Values:
<0.35 kU/L
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
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proteins. There are also hereditary forms of amyloidosis. The hereditary amyloidoses comprise a group of
autosomal dominant, late-onset diseases that show variable penetrance. A number of genes have been
associated with hereditary forms of amyloidosis including those that encode transthyretin, apolipoprotein
AI, apolipoprotein AII, fibrinogen alpha chain, cystatin C, lysozyme, and gelsolin. Apolipoprotein AI,
apolipoprotein AII, lysozyme, and fibrinogen amyloidosis present as non-neuropathic systemic
amyloidosis, with renal dysfunction being the most prevalent manifestation. Gelsolin (GSN) amyloidosis
(amyloidosis V) is characterized by corneal lattice dystrophy, cranial neuropathy, and skin changes.
Peripheral neuropathy may be present but is typically mild. Like the other hereditary amyloidoses, it is an
autosomal dominant disorder; however, homozygosity has been reported and is associated with
accelerated renal disease. Due to the clinical overlap between the acquired and hereditary forms, it is
imperative to determine the specific type of amyloidosis in order to provide an accurate prognosis and
consider appropriate therapeutic interventions. Tissue-based, laser capture tandem mass spectrometry
might serve as a useful test preceding gene sequencing to better characterize the etiology of the
amyloidosis, particularly in cases that are not clear clinically.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for
standards of interpretation and reporting of sequence variations: revisions 2007. Genet Med
2008;10(4):294-300 2. Benson MD: The hereditary amyloidoses. Best Pract Res Clin Rhematol
2003;17:909-927 3. Kiuru S: Gelsolin-related familial amyloidosis, Finnish type (FAF), and its variants
found worldwide. Amyloid 1998;5:55-66 4. Shiller SM, Dogan A, Highsmith WE: Laboratory methods
for the diagnosis of hereditary amyloidoses. In Amyloidosis-Mechanisms and Prospects for Therapy.
Edited by S Sarantseva. InTech, 2011 pp 101-120
Units: ug/mL
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Useful For: Monitoring adequacy of drug clearance during gentamicin therapy
Interpretation: Goal levels depend on the type of infection being treated. Peak targets are generally
between 5.0 and 8.0 mcg/mL for less severe infections and 8.0 and 10.0 mcg/mL for severe infections.
Prolonged exposure to peak levels exceeding 12.0 mcg/mL may lead to toxicity.
Reference Values:
Peak: 3.0-12.0 mcg/mL
Toxic peak: >12.0 mcg/mL
Useful For: Monitoring adequacy of serum concentration during gentamicin therapy This test is used
whenever a specimen is submitted or collected without collection timing information
Interpretation: Goal peak concentrations levels depend on the type of infection being treated. Goal
trough levels should be <2.0 mcg/mL. Peak targets are generally between 3.0 and 12.0 mcg/mL for
conventional dosing. Prolonged exposure to either peak levels exceeding 12.0 mcg/mL or to trough levels
exceeding 2.0 mcg/mL may lead to toxicity.
Reference Values:
Gentamicin, Peak
Therapeutic: 3.0-12.0 mcg/mL
Toxic: >12.0 mcg/mL
Gentamicin, Trough
Therapeutic: <2.0 mcg/mL
Toxic: >2.0 mcg/mL
Reference Values:
Therapeutic: <2.0 mcg/mL
Toxic: >2.0 mcg/mL
Clinical References: 1. Wilson JW, Estes LL: Mayo Clinic Antimicrobial Therapy Quick Guide,
2008 2. Hammett-Stabler CA, Johns T: Laboratory guidelines for monitoring of antimicrobial drugs.
Clin Chem 1998 May;44(5):1129-1140 3. Gonzalez LS III, Spencer JP: Aminoglcosides: a practical
review. Am Fam Physician 1998 Nov 15;58(8):1811-1820
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
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0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Supporting the diagnosis of germ cell tumors when used in conjunction with an anatomic
pathology consultation
Interpretation: A neoplastic clone is detected when the percent of cells with an abnormality exceeds
the normal cutoff for the i(12p) probe set. A positive result is consistent with the diagnosis of a germ cell
tumors (GCT). A negative result suggests that the i(12p) marker is not present, but does not exclude the
diagnosis of a GCT.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Wehle D, Yonescu R, Long PP, et al: Fluorescence in situ hybridization of
12p in germ cell tumors using a bacterial artificial chromosome clone 12p probe on paraffin-embedded
tissue: clinical test validation. Cancer Genet Cytogenet 2008 June;183(2):99-104 2. Poulos C, Cheng L,
Zhang S, et al: Analysis of ovarian teratomas for Isochromosome 12p: evidence supporting a dual
histogenetic pathway for teratomatous elements. Mod Pathology 2006;19:766-771 3. Chaganti RS,
Houldsworth J: Genetics and biology of adult human male germ cell tumors. Cancer Res. 2000 Mar
15;60(6):1475-82.
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Clinical Information: Germinal center B-cell expressed transcript 1 (GCET1), is also known as
Centerin and SERPIN9 (serine protease inhibitor). GCET1 is expressed in B cells in the germinal center
of normal lymph node and tonsil tissues. Most follicular lymphomas strongly express GCET1. In
addition, a proportion of diffuse large B-cell lymphomas (DLBCL) are positive. In the diagnosis of
B-cell lymphomas, GCET1 can be useful in an immunohistochemical panel to assign a germinal center
phenotype.
Clinical References: 1. Choi WWL, Weisenburger DD, Greiner TC, et al: A new immunostain
algorithm classifies diffuse large b-cell lymphoma into molecular subtypes with high accuracy. Clin
Cancer Res 2009;15(17):5494-5502 2. Paterson MA, Hosking PS, Coughlin PB, et al: Expression of the
serpin centerin defines a germinal center phenotype in b-cell lymphomas. Am J Clin Pathol
2008;130:117-126 3. Montes-Moreno S, Roncador G, Maestre L, et al: GCET1 (centerin), a highly
restricted marker for a subset of germinal center-derived lymphomas. Blood 2008;111(1):351-368
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 931
wheat proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
INTERPRETIVE CRITERIA:
<1:16 Antibody Not Detected
1:16 Equivocal; submission of a second specimen (collected 3-4 weeks after initial specimen) suggested
if clinically warranted
> or = 1:32 Antibody Detected
A polyvalent conjugate (recognizing IgG, IgM and IgA) is used to detect the presence of antibodies to
Giardia lamblia. A four-fold or greater increase in titer between acute and convalescent sera indicates an
acute active phase. A single positive reaction represents previous exposure, since antibody titers are
known to remain high for at least six months.
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Giardiasis is the most common intestinal parasitic infection in the United States that is reported to the
CDC and is a common cause of diarrhea in children (especially in day care centers), travelers, and
campers. It is also responsible for waterborne epidemics. Although G lamblia may be detected using the
microscopy-based stool parasitic exam (OAP / Parasitic Examination), up to 7 specimens may be
necessary for optimal sensitivity. Instead, this test detects antigen using an enzyme-linked immunosorbent
assay (ELISA), which is a more sensitive method for detection and is, therefore, a preferred method for
detection. See Parasitic Investigation of Stool Specimens Algorithm and Laboratory Testing for Infectious
Causes of Diarrhea in Special Instructions for other diagnostic tests that may be of value in evaluating
patients with diarrhea.
Useful For: Sensitive screening for the detection of Giardia lamblia antigens present in stool
specimens
Reference Values:
Negative
Clinical References: 1. Janoff EN, Craft JC, Pickering LK, et al: Diagnosis of Giardia lamblia
infections by detection of parasite-specific antigens. J Clin Microbiol 1989;27:431-435 2. Hanson KL,
Cartwright CP. Use of an enzyme immunoassay does not eliminate the need to analyze multiple stool
specimens for sensitive detection of Giardia lamblia. J Clin Microbiol 2001;39(2):474-477
Recent or current infection by Giardia lamblia is suggested by either detection of IgM antibody or a
four-fold increase in IgG and/or IgA antibody titers between acute and convalescent sera. Positive IgG
and/or IgA titers without detectable IgM suggest past infection.
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
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Interpretation: Detection of IgE antibodies in serum (Class 1 or greater) indicates an increased
likelihood of allergic disease as opposed to other etiologies and defines the allergens that may be
responsible for eliciting signs and symptoms. The level of IgE antibodies in serum varies directly with the
concentration of IgE antibodies expressed as a class score or kU/L.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: Diagnosis and management of patients with gastrointestinal stromal tumors (GIST)
Interpretation: An interpretive report will be provided.
Reference Values:
An interpretative report will be provided.
Clinical References: 1. Schildhaus HU, Cavlar T, Binot E, et al: Inflammatory fibroid polyps
harbour mutations in the platelet-derived growth factor receptor alpha (PDGFRA) gene. J Pathol
2008;216(2):176-182 2. Robson ME, Blogowski E, Sommer G, et al: Pleomorphic characteristics of a
germ-line KIT mutation in a large kindred with gastrointestinal stromal tumors, hyperpigmentation, and
dysphagia. Clin Cancer Res 2004;10:1250-1254 3. Li FP, Fletcher JA, Heinrich MC, et al: Familial
gastrointestinal stromal tumor syndrome: phenotypic and molecular features in a kindred. J Clin Oncol
2005;23:2735-2743 4. Corless CL, Fletcher JA, Heinrich MC: Biology of gastrointestinal stromal tumors.
J Clin Oncol 2004;22:3813-3825 5. Debiec-Rychter M, Raf Sciot R, Le Cesne A, et al: KIT mutations and
dose selection for imatinib in patients with advanced gastrointestinal stromal tumors. Eur J Cancer
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 934
2006;42:1093-1103 6. Heinrich MC, Corless CL, Demetri GD, et al: Kinase mutations and imatinib
mesylate response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol
2003;21:4342-4349 7. Debiec-Rychter M, Dumez H, Judson I, et al: Use of c-KIT/PDGFRA mutational
analysis to predict the clinical response to imatinib in patients with advanced gastrointestinal stromal
tumors entered on phase I and II studies of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J
Cancer 2004;40:689-695
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patient situation. Algorithms for the cascade tests are available in Special Instructions. -CDCOM /
Celiac Disease Comprehensive Cascade: complete testing including HLA DQ -CDSP / Celiac Disease
Serology Cascade: complete testing excluding HLA DQ -CDGF / Celiac Disease Gluten-Free Cascade:
for patients already adhering to a gluten-free diet To order individual tests, see Celiac Disease
Diagnostic Testing Algorithm in Special Instructions.
Useful For: Evaluating patients suspected of having celiac disease; this includes patients with
symptoms compatible with celiac disease, patients with atypical symptoms, and individuals at increased
risk of celiac disease Evaluating the response to treatment with a gluten-free diet
Interpretation: Positive test results for deamidated gliadin antibodies, IgA or IgG, are consistent with
the diagnosis of celiac disease. Negative results indicate a decreased likelihood of celiac disease.
Decreased levels of deamidated gliadin antibodies, IgA or IgG, following treatment with a gluten-free diet
are consistent with adherence to the diet. Persistence of high levels of antibodies following dietary
treatment suggest poor adherence to the diet or the presence of refractory disease. See Celiac Disease
Diagnostic Testing Algorithm in Special Instructions for the recommended approach to a patient
suspected of celiac disease. An algorithm is available for monitoring the patient's response to treatment,
see Celiac Disease Routine Treatment Monitoring Algorithm in Special Instructions.
Reference Values:
Negative: <20.0 U
Weak positive: 20.0-30.0 U
Positive: >30.0 U
Reference values apply to all ages.
Clinical References: 1. Green PH, Cellier C: Celiac disease. New Engl J Med 2007;357:1731-1743
2. Green PH, Jabri B: Celiac disease. Annu Rev Med 2006;57:207-221 3. Harrison MS, Wehbi M,
Obideen K: Celiac disease: More common than you think. Cleve Clin J Med 2007;74:209-215 4. Dale JC,
Homburger HA, Masoner DE, et al: Update on celiac disease: New standards and new tests. Mayo
Communique 2008;33(6):1-9 5. Rashtak S, Ettore MW, Homburger HA, et al: Comparative usefulness of
deamidated gliadin antibody measurements in the diagnosis of celiac disease. Clin Gastroenterol Hepatol
2008 Apr;6(4):426-432 6. Sugai E, Vazquez H, Nachman F, et al: Accuracy of testing for antibodies to
synthetic gliadin-related peptides in celiac disease. Clin Gastroenterol Hepatol 2006;4:1112-1117
Useful For: Evaluating patients suspected of having celiac disease; this includes patients with
symptoms compatible with celiac disease, patients with atypical symptoms, and individuals at increased
risk of celiac disease Evaluating the response to treatment with a gluten-free diet
Interpretation: Positive test results for deamidated gliadin antibodies, IgA or IgG, are consistent
with the diagnosis of celiac disease. Negative results indicate a decreased likelihood of celiac disease.
Decreased levels of deamidated gliadin antibodies, IgA or IgG, following treatment with a gluten-free
diet are consistent with adherence to the diet. Persistence of high levels of antibodies following dietary
treatment suggest poor adherence to the diet or the presence of refractory disease. See Celiac Disease
Diagnostic Testing Algorithm in Special Instructions for the recommended approach to a patient
suspected of celiac disease. An algorithm is available for monitoring the patient's response to treatment,
see Celiac Disease Routine Treatment Monitoring Algorithm in Special Instructions.
Reference Values:
Negative: <20.0 U
Weak positive: 20.0-30.0 U
Positive: >30.0 U
Reference values apply to all ages.
Clinical References: 1. Green PH, Cellier C: Celiac disease. New Eng J Med 2007;357:1731-1743
2. Green PH, Jabri B: Celiac disease. Annu Rev Med 2006;57:207-221 3. Harrison MS, Wehbi M,
Obideen K: Celiac disease: More common than you think. Cleve Clin J Med 2007;74:209-215 4. Dale
JC, Homburger HA, Masoner DE, Murray JA: Update on celiac disease: New standards and new tests.
Mayo Communique 2008;33(6):1-9 5. Rashtak S, Ettore MW, Homburger HA, Murray JA:
Comparative usefulness of deamidated gliadin antibodies in the diagnosis of celiac disease. Clin
Gastroenterol Hepatol 2008 Apr;6(4):426-432 6. Sugai E, Vazquez H, Nachman F, et al: Accuracy of
testing for antibodies to synthetic gliadin-related peptides in celiac disease. Clin Gastroenterol Hepatol
2006;4:1112-1117
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 937
DGGL Gliadin (Deamidated) Antibody, IgG, Serum
89030 Clinical Information: Celiac disease (gluten-sensitive enteropathy, celiac sprue) results from an
immune-mediated inflammatory process that occurs in genetically susceptible individuals following
ingestion of wheat, rye, or barley proteins.(1) The inflammation in celiac disease occurs primarily in the
mucosa of the small intestine, which leads to villous atrophy.(1) Common clinical manifestations related
to gastrointestinal inflammation include abdominal pain, malabsorption, diarrhea, and/or constipation.(2)
Clinical symptoms of celiac disease are not restricted to the gastrointestinal tract. Other common
manifestations of celiac disease include failure to grow (delayed puberty and short stature), iron
deficiency, recurrent fetal loss, osteoporosis, chronic fatigue, recurrent aphthous stomatitis (canker sores),
dental enamel hypoplasia, and dermatitis herpetiformis.(3) Patients with celiac disease may also present
with neuropsychiatric manifestations including ataxia and peripheral neuropathy, and are at increased risk
for development of non-Hodgkin lymphoma.(1,2) The disease is also associated with other clinical
disorders including thyroiditis, type I diabetes mellitus, Down syndrome, and IgA deficiency.(1,3) Celiac
disease tends to occur in families; individuals with family members who have celiac disease are at
increased risk of developing the disease. Genetic susceptibility is related to specific HLA markers. More
than 97% of individuals with celiac disease in the United States have DQ2 and/or DQ8 HLA markers,
compared to approximately 40% of the general population.(3) A definitive diagnosis of celiac disease
requires a jejunal biopsy demonstrating villous atrophy.(1-3) Given the invasive nature and cost of the
biopsy, serologic tests may be used to identify individuals with a high probability of having celiac disease.
Because no single laboratory test can be relied upon completely to establish a diagnosis of celiac disease,
those individuals with positive laboratory results should be referred for small intestinal biopsy, thereby
decreasing the number of unnecessary invasive procedures. Celiac disease is associated with a variety of
autoantibodies, including endomysial, tissue transglutaminase (tTG), and deamidated gliadin
antibodies.(4) Although the IgA isotype of these antibodies usually predominates in celiac disease,
individuals may also produce IgG isotypes, particularly if the individual is IgA deficient.(2) The most
sensitive and specific serologic tests are tTG and deamidated gliadin antibodies. Testing for IgA and IgG
antibodies to unmodified gliadin proteins is no longer recommended because of the low sensitivity and
specificity of these tests for celiac disease; however, recent studies have identified specific B-cell epitopes
on the gliadin molecule that, when deamidated by the enzyme tissue transglutaminase, have increased
sensitivity and specificity for celiac disease.(5,6) The tests for deamidated gliadin antibodies, IgA and
IgG, replace the older gliadin antibody tests, which have been discontinued at Mayo Clinic. The
sensitivity and specificity of test DGLDN / Gliadin (Deamidated) Antibodies Evaluation, IgG and IgA,
Serum for untreated, biopsy-proven celiac disease were comparable to TSTGP / Tissue Transglutaminase
(tTG) Antibodies, IgA and IgG Profile, Serum in a recent study conducted at Mayo Clinic.(5) The
treatment for celiac disease is maintenance of a gluten-free diet.(1-3) In most patients who adhere to this
diet, levels of associated autoantibodies decline and villous atrophy improves. This is typically
accompanied by an improvement in clinical symptoms. For evaluation purposes, all serologic tests
ordered for the diagnosis of celiac disease should be performed while the patient is on a gluten-containing
diet. Once a patient has initiated the gluten-free diet, serologic testing may be repeated to assess the
response to treatment. In some patients, it may take up to 1 year for antibody titers to normalize.
Persistently elevated results suggest poor adherence to the gluten-free diet or the possibility of refractory
celiac disease.(1) See Celiac Disease Diagnostic Testing Algorithm in Special Instructions for the
recommended approach to a patient suspected of celiac disease. An algorithm is available for monitoring
the patient's response to treatment, see Celiac Disease Routine Treatment Monitoring Algorithm in
Special Instructions. For your convenience, we recommend utilizing cascade testing for celiac disease.
Cascade testing ensures that testing proceeds in an algorithmic fashion. The following cascades are
available; select the appropriate one for your specific patient situation. Algorithms for the cascade tests
are available in Special Instructions. -CDCOM / Celiac Disease Comprehensive Cascade: complete
testing including HLA DQ -CDSP / Celiac Disease Serology Cascade: complete testing excluding HLA
DQ -CDGF / Celiac Disease Gluten-Free Cascade: for patients already adhering to a gluten-free diet To
order individual tests, see Celiac Disease Diagnostic Testing Algorithm in Special Instructions.
Useful For: Evaluating patients suspected of having celiac disease; this includes patients with
symptoms compatible with celiac disease, patients with atypical symptoms, and individuals at increased
risk of celiac disease Evaluating the response to treatment with a gluten-free diet
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 938
Interpretation: Positive test results for deamidated gliadin antibodies, IgA or IgG, are consistent
with the diagnosis of celiac disease. Negative results indicate a decreased likelihood of celiac disease.
Decreased levels of deamidated gliadin antibodies, IgA or IgG, following treatment with a gluten-free
diet are consistent with adherence to the diet. Persistence of high levels of antibodies following dietary
treatment suggest poor adherence to the diet or the presence of refractory disease.
Reference Values:
Negative: <20.0 U
Weak positive: 20.0-30.0 U
Positive: >30.0 U
Reference values apply to all ages.
Clinical References: 1. Green PH, Cellier C: Celiac disease. New Eng J Med 2007;357:1731-1743
2. Green PH, Jabri B: Celiac disease. Annu Rev Med 2006;57:207-221 3. Harrison MS, Wehbi M,
Obideen K: Celiac disease: More common than you think. Cleve Clinic J Med 2007;74:209-215 4. Dale
JC, Homburger HA, Masoner DE, Murray JA: Update on celiac disease: New standards and new tests.
Mayo Communique 2008;33(6):1-9 5. Rashtak S, Ettore MW, Homburger HA, Murray JA:
Comparative usefulness of deamidated gliadin antibodies in the diagnosis of celiac disease. Clin
Gastroenterol Hepatol 2008 Apr;6(4):426-432 6. Sugai E, Vazquez H, Nachman F, et al: Accuracy of
testing for antibodies to synthetic gliadin-related peptides in celiac disease. Clin Gastroenterol Hepatol
2006;4:1112-1117
Clinical References: 1. Halliday GM, Cullen KM, Kril JJ, et al: Glial fibrillary acidic protein
(GFAP) immunohistochemistry in human cortex: A quantitative study using different antisera. Nuerosci
Lett 1996;209(1):29-32 2. Meis JM, Ho KL, Nelson JS: Gliosarcoma: A histologic and
immunohistochemical reaffirmation. Modern Pathology 1990;3(1): 19-24 3. Paulus W: GFAP, Ki67 and
IDH1: Perhaps the golden triad of glioma immunohistochemistry. Acta Neuropathol 2009;118:603-604
4. Santos GC, Carvalho KC, Falzoni R, et al: Glial fibrillary acidic protein in tumor types with
cartilaginous differentiation. Modern Pathology 2009;22:1321-1327
Plasma insulin concentrations have been shown to increase only when plasma glipizide concentrations
exceeded 200 ng/mL.
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Toxic range has not been established.
Useful For: Evaluating patients with rapid onset renal failure or pulmonary hemorrhage, as an aid in
the diagnosis of Goodpasture syndrome
Interpretation: Positive results are consistent with Goodpasture syndrome. Glomerular basement
membrane antibodies detected by immunoassay have been reported to be highly specific for Goodpasture
syndrome. The sensitivity of this test approaches 87% in untreated patients with systemic disease.(1)
Reference Values:
<1.0 U (negative)
> or =1.0 U (positive)
Reference values apply to all ages.
Clinical References: 1. Pusey CD: Anti-glomerular basement membrane disease. Kidney Int
2003;64:1535-1550
Useful For: An aid in the study of islet-cell tumors and some endocrine tumors of the gastrointestinal
tract
Interpretation: This test includes only technical performance of the stain (no pathologist interpretation
is performed). If diagnostic consultation by a pathologist is required order 70012 / Pathology
Consultation. The positive and negative controls are verified as showing appropriate immunoreactivity. If
a control tissue is not included on the slide, a scanned image of the relevant quality control tissue is
available upon request. Please contact 1-855-516-8404. Interpretation of this test should be performed in
the context of the patient's clinical history and other diagnostic tests by a qualified pathologist.
Useful For: Diagnosis and follow-up of glucagonomas and other glucagon-producing tumors
Assessing diabetic patients with problematic hyper- or hypoglycemic episodes (extremely limited
utility) Glucagon is routinely measured along with serum glucose, insulin, and C-peptide levels, during
the mixed-meal test employed in the diagnostic workup of suspected postprandial hypoglycemia.
However, it plays only a minor role in the interpretation of this test.
Interpretation: Elevated glucagon levels in the absence of hypoglycemia may indicate the presence
of a glucagon-secreting tumor. Successful treatment of a glucagon-secreting tumor is associated with
normalization of glucagon levels. Inappropriate elevations in glucagon levels in hyperglycemic type I
diabetic patients indicate that paradoxical glucagon release may contribute to disease severity. This can
be observed if insulin treatment is inadequate and patients are ketotic. However, glucagon measurement
plays little, if any, role in the diagnostic workup of diabetic ketoacidosis, which is based on
demonstrating significantly elevated plasma or serum glucose (>250 mg/dL), circulating ketones
(beta-hydroxy butyrate), and acidosis (typically with increased anion gap). In diabetic patients, low
glucagon levels (undetectable or in the lower quartile of the normal range) in the presence of
hypoglycemia indicate impairment of hypoglycemic counter-regulation. These patients may be
particularly prone to recurrent hypoglycemia. This can be a permanent problem due to islet alpha-cell
destruction or other, less well understood processes (eg, autonomous neuropathy). It can also be
functional, most often due to over tight blood-glucose control, and may be reversible after decreasing
insulin doses.
Reference Values:
< or =6 hours: 100-650 pg/mL
1-2 days: 70-450 pg/mL
2-4 days: 100-650 pg/mL
4-14 days: declining gradually to adult levels
>14 days: < or =80 pg/mL (range based on 95% confidence limits)
Glucagon levels are inversely related to blood glucose levels at all ages. This is particularly
pronounced at birth and shortly thereafter, until regular feeding patterns are established. This explains
the higher levels immediately after birth, which then first fall as the glucagon release mobilizes the
infant's glucose stores, then rise again as stores are depleted, finally normalizing towards adult levels as
regular feeding patterns are established.
Clinical References: 1. Sherwood NM, Krueckl SL, McRory JE: The origin and function of the
pituitary adenylate cyclase-activating polypeptide (PACAP)/glucagon superfamily. Endocrin Rev 2000
Dec;21(6):619-670 2. Tomassetti P, Migliori M, Lalli S, et al: Epidemiology, clinical features and
diagnosis of gastroenteropancreatic endocrine tumours. Ann Oncol 2001;12 Suppl 2:S95-99 3. Cryer
PE: Hypoglycemia risk reduction in type 1 diabetes. Exp Clin Endocrinol Diabetes 2001;109 Suppl
2:S412-423 4. Jhiang G, Zhang BB: Glucagon and regulation of glucose metabolism. Am J Physiol
Metab 2003;284:E671-E678 5. vanBeek AP, de Haas ER, van Vloten WA, et al: The glucagonoma
syndrome and necrolytic migratory erythema: a clinical review. Eu J Endocrinol 2004;151:531-537
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GPSY Glucopsychosine, Blood Spot
62236 Clinical Information: Gaucher disease is an autosomal recessive lysosomal storage disorder caused
by a deficiency of the enzyme, beta-glucosidase. Beta-glucosidase facilitates the lysosomal degradation of
glucosylceramide (glucocerebroside) and glucopsychosine (glucosylsphingosine). Gaucher disease is
caused by mutations in the GBA gene. There are 3 described types of Gaucher disease with varying
clinical presentations and age of onset from a perinatal lethal disorder to an asymptomatic type. Features
of all types of Gaucher disease include hepatosplenomegaly and hematological abnormalities. Gaucher
disease type I is the most common, representing more than 90% of cases. It is generally characterized by
bone disease, hepatosplenomegaly, anemia and thrombocytopenia, coagulation abnormalities, lung
disease, but no central nervous system (CNS) involvement. Gaucher disease types II and III are
characterized by the presence of primary neurologic disease. In addition, Type II typically presents with
limited psychomotor development, hepatosplenomegaly, and lung disease, resulting in death usually
between 2 and 4 years of age. Individuals with Gaucher disease type III may present prior to 2 years of
age, but the progression is not as rapid and patients may survive into the third and fourth decade. Further
subtypes of Gaucher disease include a perinatal lethal form associated with skin abnormalities and
nonimmune hydrops fetalis, and a cardiovascular form presenting with calcification of the aortic and
mitral valves, mild splenomegaly, corneal opacities, and gaze impairment. Treatment is available in the
form of enzyme replacement therapy and/or substrate reduction therapy for types I and III. These
treatment options have generally made bone marrow transplantation obsolete. Currently, only supportive
therapy is available for type II because of the inability of enzyme provided by replacement therapy to
cross the blood-brain barrier. The incidence of Gaucher disease type I ranges from 1 in 30,000 to 1 in
100,000 in the general population, but is much more frequent among Ashkenazi Jews with an incidence of
approximately 1 in 900. Types II and III both have an incidence of approximately 1 in 100,000 in the
general population. A diagnostic workup for Gaucher disease may demonstrate the characteristic finding
of Gaucher cells on bone marrow examination, other hematologic abnormalities, and
hepatosplenomegaly. The diagnosis can be confirmed by the demonstration of reduced or absent acid
beta-glucosidase activity in leukocytes (BGL / Beta-Glucosidase, Leukocytes) and molecular genetic
analysis of the GBA gene (GAUP / Gaucher Disease, Mutation Analysis, GBA; or GBAZ / Gaucher
Disease, Full Gene Analysis). Glucopsychosine is elevated in symptomatic patients and supports a
diagnosis of Gaucher disease. It may also be helpful in determining treatment response.
Useful For: Quantification of glucopsychosine (glucosylsphingosine) in dried blood spots supports the
biochemical diagnosis of Gaucher disease May aid in monitoring a patients response to treatment
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Useful For: A second-order test in the evaluation of individuals with chronic hemolysis
Interpretation: Glucose phosphate isomerase (GPI) deficiency causes a moderately severe anemia.
GPI values can be 25% of normal. Increased GPI activity may be seen when young red blood cells are
being produced in response to the anemia (reticulocytosis) or in the case of a newborn.
Reference Values:
> or =12 months: 39.3-57.7 U/g Hb
Reference values have not been established for patients who are <12 months of age.
Clinical References: Fairbanks VF, Klee GG: Biochemical aspects of hematology. In Tietz
Textbook of Clinical Chemistry. Third Edition. Edited by CA Burtis, ER Ashwood, Philadelphia, WB
Saunders Company, 1999, pp 1642-1646
Reference Values:
< or =0.15 g/24 hours
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polyuria, abnormally elevated blood and urine glucose values, excessive thirst, constant hunger, sudden
weight loss, and possibly elevated blood and urine ketones. Complications from diabetes are the third
leading cause of death in the United States. There are approximately 16 million diabetics in the United
States, and that number is growing. It is estimated that at least 5 million of these people have not been
diagnosed. The prevalence in the population age 65 and older is 18.4%, representing 6.3 million cases.
The cost of diabetes to the US economy exceeds $92 billion annually. Overproduction or excess
administration of insulin causes a decrease in blood glucose to levels below normal. In severe cases, the
resulting extreme hypoglycemia is followed by muscular spasm and loss of consciousness, known as
insulin shock.
Useful For: Diagnosing and managing diabetes mellitus and other carbohydrate metabolism disorders
including gestational diabetes, neonatal hypoglycemia, idiopathic hypoglycemia, and pancreatic islet cell
carcinoma
Interpretation: Any of the following results, confirmed on a subsequent day, can be considered
diagnostic for diabetes: -Fasting plasma or serum glucose > or =126 mg/dL after an 8-hour fast -2-Hour
plasma or serum glucose > or =200 mg/ dL during a 75-gram oral glucose tolerance test (OGTT)
-Random glucose >200 mg/dL, plus typical symptoms Patients with "impaired" glucose regulation are
those whose fasting serum or plasma glucose fall between 101 and 126 mg/dL, or whose 2-hour value on
oral glucose tolerance test fall between 140 and 199 mg/dL. These patients have a markedly increased risk
of developing type 2 diabetes and should be counseled for lifestyle changes and followed up with more
testing. Indications for screening and testing include strong family history, marked obesity, history of
babies over 9 pounds, and recurrent skin and genitourinary infections. Glucose levels < or =25 mg/dL in
infants <1 week are considered to be potentially life threatening; as are glucose levels < or =40 mg/dL in
infants >1 week. Glucose levels > or =400 mg/dL are considered a critical value.
Reference Values:
0-11 months: not established
> or =1 year: 70-140 mg/dL
Clinical References: Tietz Textbook of Clinical Chemistry. Fourth edition. Edited by CA Burtis, ER
Ashwood, DE Bruns. WB Saunders Company, Philadelphia, 2006,25:837-907
Useful For: An indicator of abnormal proximal tubule function Limited usefulness in the screening or
management of diabetes mellitus
Interpretation: Elevated urine glucose concentration reflects either the presence of hyperglycemia or a
defect in proximal tubule function. As a screening test for diabetes mellitus, urine glucose testing has a
low sensitivity (though reasonably good specificity).
Reference Values:
< or =15 mg/dL
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Clinical References: Tietz Textbook of Clinical Chemistry, Third edition. Edited by CA Burtix,
ER Ashwood. Philadelphia, WB Saunders Company, 1999
Reference Values:
Spinal fluid glucose concentration should be approximately 60% of the plasma/serum concentration and
should be compared with concurrently measured plasma/serum glucose for adequate clinical
interpretation.
Clinical References: Tietz Textbook of Clinical Chemistry. Fourth edition. Edited by CA Burtis,
ER Ashwood, D Burns. Philadelphia, WB Saunders Company, 2006 pp 837-891
Interpretation: Abnormal values are usually 0% to 20% of normal mean. Intermediate values can
occur in some genetic variants and in female carriers.
Reference Values:
> or =12 months: 8.8-13.4 U/g Hb
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Reference values have not been established for patients who are <12 months of age.
Clinical References: 1. Relling MV, McDonagh EM, Chang T, et al: Clinical Pharmacogenetics
Implementation Consortium (CPIC) guidelines for rasburicase therapy in the context of G6PD deficiency
genotype. Clin Pharmacol Ther 2014 Aug;96(2):169-174 2. Beutler E: Glucose-6-phosphate
dehydrogenase deficiency. In Hematology. Fifth Edition. Edited by E Beutler, MA Lichtman, BS Coller,
TJ Kipps. New York, McGraw-Hill Book Company, 1995, pp 564-586
Useful For: Genetic test for individuals at high risk for G6PD deficiency (for initial or time-sensitive
screening for G6PD deficiency, refer to phenotyping enzyme assay G6PD / Glucose-6-Phosphate
Dehydrogenase [G-6-PD], Quantitative, Erythrocytes) Aiding in the diagnosis of glucose-6-phosphate
dehydrogenase (G6PD) deficiency Determining G6PD deficiency status in individuals with inconclusive
or unexpected phenotyping results Differentiation of heterozygous females with skewed X-inactivation
from homozygous and compound heterozygous females Definitive diagnosis of carrier status in females
Evaluation of neonates (particularly males) with unexplained jaundice Identifying individuals at risk of
drug-induced acute hemolytic anemia (AHA) related to G6PD deficiency
Interpretation: All detected alterations will be evaluated according to the latest American College of
Medical Genetics recommendations.(1) Variants will be classified based on known, predicted, or possible
effect on gene pathogenicity and reported with interpretive comments detailing their potential or known
significance.
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Reference Values:
An interpretive report will be provided.
Clinical References: 1. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the
interpretation of sequence variants: a joint consensus recommendation of the American College of
Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med
2015;(17):105-423 Available at
https://www.acmg.net/docs/Standards_Guidelines_for_the_Interpretation_of_Sequence_Variants.pdf 2.
Cappellini MD, Fiorelli G: Glucose-6-phosphate dehydrogenase deficiency. Lancet 2008;371:64-67 3.
Luzzatto L, Seneca E: G6PD deficiency: a classic example of pharmacogenetics with on-going clinical
implications. Br J Haematol 2014;164:469-480 4. OMIM 305900 Glucose-6-phosphate dehydrogenase.
Available at http://www.omim.org/entry/305900 5. Relling MV, McDonagh EM, Chang T, et al:
Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for rasburicase therapy in the
context of G6PD deficiency genotype. Clin Pharmacol Ther 2014 Aug;96(2):169-174
Clinical References: 1. Haber RS, Rathan A, Weiser KR, et al: GLUT1 glucose transporter
expression in colorectal carcinoma-a marker for poor prognosis. Cancer 1998;83(1):34-40 2. Goldman
NA, Katz EB, Glenn AS, et al: GLUT1 and GLUT8 in endometrium and endometrial adenocarcinoma.
Modern Pathology 2006;19:1429-1436 3. Chung JH, Cho KJ, Lee S, et al: Overexpression of glut 1 in
lymphoid follicles correlates with false-positive f-fdg pet results in lung cancer staging. J Nuel Med
2004;45:999-1003
Useful For: Assessing susceptibility to autoimmune (type 1, insulin-dependent) diabetes mellitus and
related endocrine disorders (eg, thyroiditis and pernicious anemia). Titers generally < or =0.02 nmol/L. A
second islet cell antibody (IA-2) is more predictive for development of type 1 diabetes, but less frequent
than glutamic acid decarboxylase (GAD65) antibody amongst diabetic patients. Insulin autoantibodies
also serve as a marker of susceptibility to type 1 diabetes. Distinguishing between patients with type 1 and
type 2 diabetes. Assays for IA-2, insulin, gastric parietal cell, thyroglobulin, and thyroid peroxidase
antibodies, complement GAD65 antibody in this context; titers generally < or =0.02 nmol/L. Confirming
a diagnosis of stiff-man syndrome, autoimmune encephalitis, cerebellitis, brain stem encephalitis,
myelitis; titers generally > or =0.03 nmol/L Confirming susceptibility to organ-specific neurological
disorders (eg, myasthenia gravis, Lambert-Eaton syndrome); titers generally < or =0.02 nmol/L
Interpretation: High titers (> or =0.02 nmol/L) are found in classic stiff-man syndrome (93% positive)
and in related autoimmune neurologic disorders (eg, acquired cerebellar ataxia, some acquired
nonparaneoplastic encephalomyelopathies). Diabetic patients with polyendocrine disorders also generally
have glutamic acid decarboxylase (GAD65) antibody values > or =0.02 nmol/L. Values in patients who
have type 1 diabetes without a polyendocrine or autoimmune neurologic syndrome are usually < or =0.02
nmol/L. Low titers (0.03-19.9 nmol/L) are detectable in the serum of approximately 80% of type 1
diabetic patients. Conversely, low titers are detectable in the serum of <5% of type 2 diabetic patients.
Low titers are found in approximately 25% of patients with myasthenia gravis, Lambert-Eaton syndrome,
and rarer autoimmune neurological disorders. Eight percent of healthy Olmsted County residents over age
50 have low-positive values. These are not false positive; the antibodies are inhibited by unlabeled
GAD65 antigen and are accompanied in at least 50% of cases by related organ-specific autoantibodies.
Values > or =0.03 nmol/L are consistent with susceptibility to autoimmune (type 1) diabetes and related
endocrine disorders (thyroiditis and pernicious anemia).
Reference Values:
< or =0.02 nmol/L
Reference values apply to all ages.
Clinical References: 1. Walikonis JE, Lennon VA: Radioimmunoassay for glutamic acid
decarboxylase (GAD65) autoantibodies as a diagnostic aid for stiff-man syndrome and a correlate of
susceptibility to type 1 diabetes mellitus. Mayo Clin Proc 1998 December;73(12):1161-1166 2. Kawasaki
E, Yu L, Gianani R, et al: Evaluation of islet cell antigen (ICA) 512/IA-2 autoantibody radioassays using
overlapping ICA512/IA-2 constructs. J Clin Endocrinol Metab 1997 February;82(2):375-380 3. Saiz A,
Arpa J, Sagasta A, et al: Autoantibodies to glutamic acid decarboxylase in three patients with cerebellar
ataxia, late-onset insulin-dependent diabetes mellitus and polyendocrine autoimmunity. Neurology 1997
October;49(4):1026-1030 4. Pittock SJ, Yoshikawa H, Ahlskog JE, et al: Glutamic acid decarboxylase
autoimmunity with brainstem, extrapyramidal and spinal cord dysfunction. Mayo Clin Proc
2006;81:1207-1214
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 948
idiopathically acquired epilepsies, some rare acquired encephalomyelopathies with and without neoplasia,
and in myasthenia gravis and Lambert-Eaton myasthenic syndrome. GAD65 antibodies account for the
majority of clinically recognized pancreatic islet cell antibodies, and are an important serological marker
of predisposition to type 1 (insulin-dependent) diabetes. GAD65 autoantibodies also serve as a marker of
predisposition to autoimmune disorders that commonly or sometimes coexist with type 1 diabetes,
including autoimmune thyroid disease (eg, thyrotoxicosis, Graves disease, Hashimoto thyroiditis,
hypothyroidism), pernicious anemia, premature ovarian failure, Addison disease (idiopathic
adrenocortical failure), and vitiligo. GAD65 antibodies are found in the serum of approximately 8% of
healthy subjects older than age 50, usually in low titer, but often accompanied by related "thyrogastric"
autoantibodies.
Useful For: Possible use in evaluating patients with stiff-man syndrome, autoimmune cerebellitis and
other acquired central nervous system disorders affecting gabaminergic neurotransmission
Interpretation: Intrathecal synthesis of GAD65 antibody has been demonstrated in patients with
stiff-man syndrome, but cerebrospinal fluid (CSF) values are log orders lower than serum. We have not
determined the frequency of GAD65 antibodies in CSF of patients with various diagnoses.
Reference Values:
< or =0.02 nmol/L
Useful For: Classification of hepatic adenomas and the identification of focal nodular hyperplasia
Interpretation: This test includes only technical performance of the stain (no pathologist
interpretation is performed). If diagnostic consultation by a pathologist is required order 70012 /
Pathology Consultation. The positive and negative controls are verified as showing appropriate
immunoreactivity. If a control tissue is not included on the slide, a scanned image of the relevant quality
control tissue is available upon request. Please contact 1-855-516-8404. Interpretation of this test should
be performed in the context of the patient's clinical history and other diagnostic tests by a qualified
pathologist.
Clinical References: 1. van Aalten SM, Verheij J, Terkivatan T, et al: Validation of a liver
adenoma classification system in a tertiary referral centre: implications for clinical practice. J Hepatol
2011;55(1):120-125 2. Bioulac-Sage P, Cubel G, Balabaud C, et al: Revisiting the pathology of resected
benign hepatocellular nodules using new immunohistochemical markers. Semin Liver Dis
2011;31(1):91-103 3. Bioulac-Sage P, Rebouissou S, Thomas C, et al: Hepatocellular adenoma subype
classification using molecular markers and immunohistochemistry. Hepatology 2007;46(3):740-748
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 949
FGLUT Gluten IgG
57559 Interpretation: mcg/mL of IgG Lower Limit of Quantitation* 2.0 Upper Limit of Quantitation** 200
Reference Values:
< 2 mcg/mL
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical utility
of food-specific IgG tests has not been established. These tests can be used in special clinical situations to
select foods for evaluation by diet elimination and challenge in patients who have food-related
complaints. It should be recognized that the presence of food-specific IgG alone cannot be taken as
evidence of food allergy and only indicates immunologic sensitization by the food allergen in question.
This test should only be ordered by physicians who recognize the limitations of the test.
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 950
TGGB Glycerol-Corrected Triglycerides, Serum
63445 Clinical Information: Triglycerides are esters of glycerol with 3 long-chain fatty acids. Increased
plasma triglyceride concentrations are indicative of a metabolic abnormality and, along with elevated
cholesterol, are considered a risk factor for atherosclerotic disease. Hyperlipidemia may be inherited or
associated with biliary obstruction, diabetes mellitus, nephrotic syndrome, renal failure, or metabolic
disorders related to endocrinopathies. Increased triglycerides may also be medication-induced (eg,
prednisone). See Lipids and Lipoproteins in Blood Plasma in Special Instructions. Traditional,
nonglycerol-blanked methods for measuring triglycerides break down plasma and serum triglycerides
into glycerol and fatty acids. The glycerol is then measured in an enzymatic colorimetric assay.
Consequently, patients with elevated free glycerol in circulation will have a falsely elevated triglyceride
concentration, pseudohypertriglyceridemia, when using a nonglycerol-blanked triglyceride assay.
Glycerol is an intermediate in the conversion of glucose to lipids and serves as the precursor for
triglyceride and other glycerolipids. Patients with type 2 diabetes mellitus, hyperthyroidism, those who
are obese, or those receiving oral or parenteral supplementation with glycerol may have slightly higher
free glycerol in circulation, however this increase is unlikely to affect triglyceride result interpretation.
Glycerol kinase deficiency (GKD) is an X-linked genetic condition leading to impaired function of
glycerol kinase (GK), the primary regulator of glycerol entry into metabolic pathways. Insufficient GK
activity leads to extreme elevations in plasma glycerol concentrations (ie, hyperglycerolemia) and
glyceroluria. Patients with GKD may be placed on a glycerol-restricted diet and instructed to avoid
prolonged periods of fasting. GKD is divided into 3 clinical forms: -Complex GKD involves mutations
in the GK locus and 2 others (adrenal hypoplasia congenital: AHC and Duchenne muscular dystrophy:
DMD) on Xp21 and manifests in infants. -Juvenile GKD is associated with metabolic and central
nervous system instability and deterioration. Juvenile GKD usually presents in the early years of life as
repeated vomiting, acidemia, and central nervous system depression. - Adult GKD is mainly benign
with detection usually found incidentally by pseudohypertriglyceridemia.
Interpretation: Patients with glycerol kinase deficiency typically have serum free glycerol
concentrations greater than 10 fold above normal.
Reference Values:
TRIGLYCERIDE, TOTAL and CORRECTED
The National Cholesterol Education Program (NCEP) has set the following guidelines in adults ages
18 and up:
Normal: <150 mg/dL
Borderline high: 150-199 mg/dL
High: 200-499 mg/dL
Very high: > or =500 mg/dL
The National Cholesterol Education Program (NCEP) and National Health and Nutrition Examination
Survey (NHANES) has set the following guidelines in children ages <2:
<2 years: Reference values have not been established for patients who are <24 months of age.
2-9 years:
Acceptable: <75 mg/dL
Borderline high: 75-99 mg/dL
High: > or =100 mg/dL
10-17 years:
Normal: <90 mg/dL
Borderline high: 90-129 mg/dL
High: > or =130 mg/dL
GLYCEROL, CALCULATED
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 951
<18 years: Reference values have not been established for patients who are <18 years of age.
>18 years: 40-370 mcmol/L
Clinical References: 1. Tietz Textbook of Clinical Chemistry. Fifth edition. Edited by CA Burtis,
ER Ashwood. Philadelphia, WB Saunders Company, 2001 2. Stinshoff K, Weisshaar D, Staehler F, et al:
Relation between concentrations of free glycerol and triglycerides in human sera. Clin Chem 1977
Jun;23(6):1029-1032 3. Sjarif DR, Ploos van Amstel JK, Duran M, et al: Isolated and contiguous glycerol
kinase gene disorders: a review. J Inherit Metab Dis 2000 Sep;23(6):529-547 4. Jacobson TA, Ito MK,
Maki KC, et al: National Lipid Association recommendations for patient-centered management of
dyslipidemia: part 1 - executive summary. J Clin Lipidol 2014 Sep-Oct;8(5):473-488 5. Expert Panel on
Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents;
National Heart, Lung, and Blood Institute: Expert panel on integrated guidelines for cardiovascular health
and risk reduction in children and adolescents. Pediatrics 2011 Dec;128 Suppl 5:S213-S256
Useful For: Follow up of abnormal biochemical results consistent with glycogen storage disease
Identifying mutations within genes known to be associated with glycogen storage disease, allowing for
predictive testing of at-risk family members
Interpretation: All detected alterations are evaluated according to American College of Medical
Genetics and Genomics recommendations.(1) Variants are classified based on known, predicted, or
possible pathogenicity and reported with interpretive comments detailing their potential or known
significance. Multiple in silico evaluation tools may be used to assist in the interpretation of these results.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 952
The accuracy of predictions made by in silico evaluation tools is highly dependent upon the data available
for a given gene, and predictions made by these tools may change over time. Results from in silico
evaluation tools should be interpreted with caution and professional clinical judgment.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for
standards for interpretation and reporting of sequence variations: Revisions 2007. Genet Med
2008;10(4):294-300 2. Chen YT, Kishani PS, Koeberl D: Glycogen Storage Disease. The Online
Metabolic and Molecular Bases of Inherited Diseases. Edited by D Valle, B Vogelstein, KW Kinzler, et
al. 3. Hicks J, Wartchow, E, Mierau G: Glycogen Storage Diseases: A Brief Review and Update on
Clinical Features, Genetic Abnormalities, Pathologic Features, and Treatmen. Ultrastruct Pathol
2011;35(5):183-196
FGLMA GlycoMark
91742 Reference Values:
Age Range
<18 y Not Established
Adult Males 10.7 32.0
Adult Females 6.8 29.3
Glycemic control goal for diabetic patients: >10
GlycoMark is intended for use with managing glycemic control in diabetic patients. A low result
corresponds to high glucose peaks.
1, 5-AG blood levels can be affected by clinical conditions or medications.
Clinical References: 1. Dong HY, Wilkes S, Yang H: CD71 is selectively and ubiquitously
expressed at high levels in erythroid precursors of all maturation stages: A comparative
immunochemical study with glycophorin A and hemoglobin A. Am J Surg Pathol 2011;35(5):723-732
2. Kurec AS, Cruz VE, Barrett D, et al: Immunophenotyping of acute leukemias using paraffin
embedded tissue. Am J Clin Pathol 1990;93(4):502-509 3. Liu W, Hasserjian RP Hu Y, et al: Pure
erythroid leukemia: A reassessment of the entity using the 2008 World Health Organization
Classification. Modern Pathology 2011;24:375-383 4. Pileri SA, Ascani S, Milani M, et al: Acute
leukaemia immunophenotyping in bone marrow routine sections. British Journal of Haematology
1999;105:394-401
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: An aid in differentiating hepatocellular carcinomas from other malignancies and hepatic
adenomas
Interpretation: This test includes only technical performance of the stain (no pathologist interpretation
is performed). If diagnostic consultation by a pathologist is required order 70012 / Pathology
Consultation. The positive and negative controls are verified as showing appropriate immunoreactivity. If
a control tissue is not included on the slide, a scanned image of the relevant quality control tissue is
available upon request. Please contact 1-855-516-8404. Interpretation of this test should be performed in
the context of the patient's clinical history and other diagnostic tests by a qualified pathologist.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 954
Clinical References: 1. Yamauchi N, Watanabe A, Hishinuma M, et al: The glypican 3 oncofetal
protein is a promising diagnostic marker for hepatocellular carcinoma. Modern Pathology 2005
Dec;18(12):1591-1598 2. Ligato S, Mandich D, Cartun RW: Utility of glypican-3 in differentiating
hepatocellular carcinoma from other primary and metastatic lesions in FNA of the liver: an
immunocytochemical study. Modern Pathology 2008 May;21 (5):626-631 3. Kandil DH, Cooper K:
Glypican-3: a novel diagnostic marker for hepatocellular carcinoma and more. Advanced Anatomic
Pathology 2009 Mar;16(2):125-129
Useful For: Molecular diagnosis or carrier status of mucolipidosis II alpha/beta and mucolipidosis III
alpha/beta in conjunction with identification of characteristic clinical, radiographic, and biochemical
findings, and genetic counseling for family members
Clinical References: 1. Kudo M, Brem MS, Canfield WM: Mucolipidosis II (I-cell disease) and
mucolipidosis IIIA (classical pseudo-hurler polydystrophy) are caused by mutations in the
GlcNAc-phosphotransferase alpha/beta-subunits precursor gene. Am J Hum Genet 2006;78:451-463 2.
Cathey SS, Leroy JG, Wood T, et al: Phenotype and genotype in mucolipidoses II and III alpha/beta: a
study of 61 probands. J Med Genet 2010;47:38-48
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 956
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 957
sensitization and clinical manifestations proceed as follows: eczema and respiratory disease (rhinitis and
bronchospasm) in infants and children less than 5 years due to food sensitivity (milk, egg, soy, and
wheat proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Reference Values:
Adult Reference Range(s):
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 959
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: Identifying microorganisms in normally sterile body fluids Screening sputum specimens
for acceptability for bacterial culture Guiding initial antimicrobial therapy
Interpretation: During the staining process, the crystal violet and iodine form a complex within the
heat fixed cell. In gram-negative organisms, this complex is readily washed out by the acetone-alcohol.
They appear red because they retain only the safranin dye (counterstain). Gram-positive organisms retain
the crystal violet-iodine complex after decolorization and remain purple.
Reference Values:
No organisms seen or descriptive report of observations.
Clinical References: Atlas RM, Snyder JW: Reagents, Stains, and Media: Bacteriology. In Manual
of Clinical Microbiology. Vol 1. 10th edition, Edited by J Versalovic. Washington DC, American Society
for Microbiology, 2011, pp 272-307
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 960
GSBV Gram Stain for Bacterial Vaginosis
61565 Clinical Information: Bacterial vaginosis is so-named because bacteria are the cause and an
associated inflammatory response is lacking. It results in an increase in thin, gray, homogeneous vaginal
discharge and vaginal malodor and is caused by a change in the vaginal flora. Bacterial vaginosis is a
synergistic polymicrobial infection not caused by a specific organism. The standard scoring system
termed the "Nugent score" is a technique for assessing bacterial vaginosis using microscopic
examination of a Gram-stained smear of vaginal discharge.
Reference Values:
One of the 3 following reports dependent on the weighted sum balance of Lactobacillus,
Gardnerella/Bacteroides, and Mobiluncus species:
1. Consistent with normal bacterial vaginal flora.
2. Altered vaginal flora not consistent with bacterial vaginosis. This frequently represents a transitional
stage. If signs or symptoms persist, repeat testing is warranted.
3. Consistent with bacterial vaginosis.
Interpretation: A negative or positive result is reported for each gene type assayed. A positive result
confirms the presence of a particular beta-lactamase gene in the bacterial isolate tested.
Reference Values:
Not applicable
Clinical References: 1. Patel JB, Richter SS: Mechanisms of resistance to antibacterial agents. In
Manual of Clinical Microbiology. 11th edition. Edited by JH Jorgensen, MA Pfaller, KC Carrol, et al.
Washington, DC, ASM Press, 2015, section 69, pp 1212-1245 2. Abbot, AN, Fange FC: Molecular
detection of antibacterial drug resistance. In Manual of Clinical Microbiology, 11th edition. Edited by JH
Jorgensen, MA Pfaller, KC Carrol, et al. Washington, DC, ASM Press, 2015, section 77, pp 1379-1389 3.
Cunningham SA, Vasoo S, Patel R: Evaluation of the Check-Points Check MDR CT103 and CT103 XL
Microarray Kits Using Preparatory Rapid Cell Lysis. J Clin Microbiol 2015;54:1368-1371
Useful For: The work-up of individuals having febrile, nonhemolytic transfusion reactions The
detection of individuals with autoimmune neutropenia
Interpretation: A positive result in an individual being worked up for a febrile transfusion reaction
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 962
indicates the need for leukocyte-poor (filtered) red blood cells. This test cannot distinguish between allo-
and autoantibodies
Reference Values:
Not applicable
Clinical References: Verheugt FW, von dem Borne AE, Decary F, Engelfreit CP: The detection of
granulocyte alloantibodies with an indirect immunofluorescence test. Br J Haematol 1997;36:533-534
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical
utility of food-specific IgG tests has not been established. These tests can be used in special clinical
situations to select foods for evaluation by diet elimination and challenge in patients who have
food-related complaints. It should be recognized that the presence of food-specific IgG alone cannot be
taken as evidence of food allergy and only indicates immunologic sensitization by the food allergen in
question. This test should only be ordered by physicians who recognize the limitations of the test.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 963
bronchospasm) in infants and children less than 5 years due to food sensitivity (milk, egg, soy, and
wheat proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 965
6 > or =100 Strongly positive Reference values
apply to all ages.
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 966
immunoglobulin E (IgE)-sensitized effector cells (mast cells and basophils) when cell-bound IgE
antibodies interact with allergen. In vitro serum testing for IgE antibodies provides an indication of the
immune response to allergen(s) that may be associated with allergic disease. The allergens chosen for
testing often depend upon the age of the patient, history of allergen exposure, season of the year, and
clinical manifestations. In individuals predisposed to develop allergic disease(s), the sequence of
sensitization and clinical manifestations proceed as follows: eczema and respiratory disease (rhinitis and
bronchospasm) in infants and children less than 5 years due to food sensitivity (milk, egg, soy, and wheat
proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 967
Clinical References: 1. Ellison DW, Dalton J, Kocak M, et al: Medulloblastoma clinicopathological
correlates of SHH, WNT, and non-SHH/WNT molecular subgroups. Acta Neuropathol 2011;121:381-396
2. Northcott PA, Korshunov A, Witt H, et al: Medulloblastoma comprises four distinct molecular variants.
J Clin Oncol 2011 Apr 10;29(11):1408-1414 3. Thompson MC, Fuller C, Hogg TL, et al: Genomics
identifies medulloblastoma subgroups that are enriched for specific genetic alterations. J Clin Oncol
2006;24:1924-931
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 968
antibodies interact with allergen. In vitro serum testing for IgE antibodies provides an indication of the
immune response to allergen(s) that may be associated with allergic disease. The allergens chosen for
testing often depend upon the age of the patient, history of allergen exposure, season of the year, and
clinical manifestations. In individuals predisposed to develop allergic disease(s), the sequence of
sensitization and clinical manifestations proceed as follows: eczema and respiratory disease (rhinitis and
bronchospasm) in infants and children less than 5 years due to food sensitivity (milk, egg, soy, and wheat
proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 969
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 970
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 971
GSTB Green String Bean, IgE
82610 Clinical Information: Clinical manifestations of immediate hypersensitivity (allergic) diseases are
caused by the release of proinflammatory mediators (histamine, leukotrienes, and prostaglandins) from
immunoglobulin E (IgE)-sensitized effector cells (mast cells and basophils) when cell-bound IgE
antibodies interact with allergen. In vitro serum testing for IgE antibodies provides an indication of the
immune response to allergen(s) that may be associated with allergic disease. The allergens chosen for
testing often depend upon the age of the patient, history of allergen exposure, season of the year, and
clinical manifestations. In individuals predisposed to develop allergic disease(s), the sequence of
sensitization and clinical manifestations proceed as follows: eczema and respiratory disease (rhinitis and
bronchospasm) in infants and children less than 5 years due to food sensitivity (milk, egg, soy, and wheat
proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 972
sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 973
analysis performed on liver biopsy; however, this has been replaced by molecular testing, which forms
the basis of confirmatory or carrier testing in most cases. PH2 is inherited as an autosomal recessive
disorder caused by mutations in the GRHPR gene, which encodes the enzyme GRHPR. Two common
GRHPR mutations have been identified: c.103delG and c.403_404+2delAAGT. These mutations
account for about one-third of the mutant alleles described in the Northern European Caucasian
population and about 15% in the Asian population. Direct sequencing of the GRHPR gene will identify
these 2 mutations as well as other less common or novel mutations associated with PH2.
Useful For: Confirming a diagnosis of primary hyperoxaluria type 2 (PH2) Carrier testing for
individuals with a family history of PH2 in the absence of known mutations in the family
Interpretation: All detected alterations will be evaluated according to American College of Medical
Genetics and Genomics (ACMG) recommendations.(1) Variants will be classified based on known,
predicted, or possible pathogenicity, and reported with interpretive comments detailing their potential or
known significance.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for
standards of interpretation and reporting of sequence variations: revisions 2007. Genet Med
2008:10(4):294-300 2. Primary Hyperoxaluria Type 2-GeneReviews-NCBI Bookshelf. Available from
URL: http://www.ncbi.nlm.nih.gov/books/NBK2692/, accessed 8-7-2012 3. Rumsby G, Williams E,
Coulter-Mackie M: Evaluation of mutation screening as a first line test for the diagnosis of the primary
hyperoxalurias. Kidney Int 2004;66(3):959-963 4. Cregeen DP, Williams EL, Hulton S, Rumsby G:
Molecular analysis of the glyoxylate reductase (GRHPR) gene and description of mutations underlying
primary hyperoxaluria type 2. Hum Mutat 2003;22(6):497 5. Laboratory and molecular diagnosis of
primary hyperoxaluria and oxalosis. Mayo Medical Laboratories' Communique, April 2007
Useful For: Diagnosis of perianal cellulitis or for screening of patients and health care workers for
Streptococcus pyogenes for the purpose of investigating possible nosocomial transmission
Useful For: Screening for maternal colonization with Streptococcus agalactiae at 35 to 37 weeks
gestation as a guide for intrapartum antibiotic prophylaxis to decrease the risk of infection by
Streptococcus agalactiae in the infant
Reference Values:
<0.35 kU/L
Interpretation: Abnormal results along with clinical findings may be suggestive of mitochondrial
disease. Additional workup is indicated.
Reference Values:
3 months* and older: < or =750 pg/mL
*This test is not recommended for infants <3 months of age due to the high levels of GDF15 contributed
from the placenta during pregnancy.
Clinical References: 1. Hamid A, Mrak RE, Ijaz M, et al: Sensitivity and specificity of
immunohistochemistry in pituitary adenomas. The Endocrinologist 2009;19(1):38-43 2. Osamura RY,
Watanabe K: Immunohistochemical colocalization of growth hormone (GH) and alpha subunit in human
GH secreting pituitary adenomas. Virchows Archiv A 1987;411(4):323-330 3. Yamada Sh, Alba T, Sano
T et al: Growth hormone-producing pituitary adenomas: Correlations between clinical characteristics and
morphology. Neurosurgery 1993;33(1):20-27
Useful For: Diagnosis of acromegaly and assessment of treatment efficacy (in conjunction with
glucose suppression test) Diagnosis of human growth hormone deficiency (in conjunction with growth
hormone stimulation test)
Interpretation: Acromegaly: For suppression testing, normal subjects have a nadir growth hormone
(GH) concentration of <0.3 ng/mL after ingestion of a 75-gram glucose dose. Patients with acromegaly
fail to show normal suppression. Using the Access ultrasensitive hGH assay, a cutoff of 0.53 ng/mL for
nadir GH was found to most accurately differentiate patients with acromegaly in remission from active
disease with a sensitivity of 97% (95% CI, 83%-100%) and a specificity of 100% (95% CI,
82%-100%).(1) Deficiency: A normal response following stimulation tests is a peak GH concentration
>5 ng/mL in children and >4 ng/mL in adults. For children, some experts consider GH values between 5
ng/mL and 8 ng/mL equivocal and only GH peak values >8 ng/mL as truly normal. Low levels,
particularly under stimulation, indicate human growth hormone deficiency.
Reference Values:
Adults
Males: 0.01-0.97 ng/mL
Females: 0.01-3.61 ng/mL
Reference intervals have not been formally verified in-house for pediatric and adolescent patients. The
published literature indicates that reference intervals for adult, pediatric, and adolescent patients are
comparable.
Reference Values:
Levels of IR-GH-RH
Baseline range: 5 - 18 pg/mL
Levels in GH-RH Dysfunction:
Patients with acromegaly: up to 200 pg/mL
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 977
Patients with small cell lung carcinoma: up to 50 pg/mL
GH-RH secreting tumors: 200 -10,000 pg/mL
This test was performed using a kit that has not been cleared or approved by the FDA and is
designated as research use only.
The analytic performance characteristics of this test have been determined by Inter Science Institute.
This test is not intended for diagnosis or patient management decisions without confirmation by other
medically established means.
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 979
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 980
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Reference Values:
<0.35 kU/L
Reference Values:
<0.35 kU/L
Reference Values:
<0.35 kU/L
Reference Values:
<0.35 kU/L
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 981
HIBS Haemophilus influenzae Type B Antibody, IgG, Serum
83261 Clinical Information: Haemophilus influenzae type B (HIB) is an encapsulated gram-negative
cocco-bacillary bacterium that can cause devastating disease in young children including meningitis,
bacteremia, cellulitis, epiglottitis, pneumonia, and septic arthritis. One of the great advances in modern
medicine has been the development of an effective vaccine against HIB. A patient's immunological
response to HIB vaccine can be determined by measuring anti-HIB IgG antibody using this EIA
technique.
Useful For: Assessing a patient's immunological (IgG) response to Haemophilus influenzae type B
(HIB) vaccine Assessing immunity against HIB Aiding in the evaluation of immunodeficiency
Reference Values:
> or =0.15 mg/L
Clinical References: 1. Dunphy CH: Reaction patterns of TRAP and DBA.44 in hairy cell leukemia,
hairy cell variant, and nodal and extranodal marginal zone B-cell lymphomas. Appl Immunohistochem
Mol Morphol 2008;16(2):135-139 2. Hoyer JD, Li CY, Yam LT, et al: Immunohistochemical
demonstration of acid phosphatase isoenzyme 5 (tartrate-resistant) in paraffin sections of hairy cell
leukemia and other hematologic disorders. Am J Clin Pathol 1997;108(3):3-8-315 3. Jones G, Parry-Jones
N, Wilkins B, et al: Revised guidelines for the diagnosis and malignant of hairy cell leukaemia and hairy
cell leukemia variant. British Journal of Haematology 2011.156:186-195 4. Sherman MJ, Hanson CA,
Hoyer JD: An assessment of the usefulness of immunohistochemical stains in the diagnosis of hairy cell
leukemia. Am J Clin Pathol 2011;136:390-399
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
The reference range listed on the report is the lower limit of quantitation for the assay. The clinical
utility of food-specific IgG tests has not been established. These tests can be used in special clinical
situations to select foods for evaluation by diet elimination and challenge in patients who have
food-related complaints. It should be recognized that the presence of food-specific IgG alone cannot be
taken as evidence of food allergy and only indicates immunologic sensitization by the food allergen in
question. This test should only be ordered by physicians who recognize the limitations of the test.
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 984
Useful For: Optimizing dosage Monitoring compliance Assessing toxicity
Interpretation: Studies show a strong relationship between dose and serum concentration (4);
however, there is a modest relationship of clinical response or risk of developing long-term side effects
to either dose or serum concentration. A therapeutic window exists for haloperidol; patients who
respond at serum concentrations between 5 to 16 ng/mL show no additional improvement at
concentrations >16 to 20 ng/mL.(3,5) Some patients may respond at concentrations <5 ng/mL, and
others may require concentrations significantly >20 ng/mL before an adequate response is attained.
Because of such inter-individual variation, the serum concentration should only be used as 1 factor in
determining the appropriate dose and must be interpreted in conjunction with the clinical status.
Although the metabolite, reduced haloperidol, has minimal pharmacologic activity, evidence has been
presented suggesting that an elevated ratio of reduced haloperidol-to-haloperidol (ie, >5) is predictive of
a poor clinical response.(3,6) A reduced haloperidol-to-haloperidol ratio <0.5 indicates noncompliance;
the metabolite does not accumulate except during steady-state conditions.
Reference Values:
HALOPERIDOL
5-16 ng/mL
REDUCED HALOPERIDOL
10-80 ng/mL
Clinical References: 1. Lawson GM: Monitoring of serum haloperidol. Mayo Clin Proc
1994;69:189-190 2. Ereshefsky L, Davis CM, Harrington CA, et al: Haloperidol and reduced
haloperidol plasma levels in selected schizophrenic patients. J Clin Psychopharmacol 1984;4:138-142 3.
Volavka J, Cooper TB: Review of haloperidol blood level and clinical response: looking through the
window. J Clin Psycho-pharmacol 1987;7:25-30 4. Moulin MA, Davy JP, Debruyne JC, et al: Serum
level monitoring and therapeutic effect of haloperidol in schizophrenic patients. Psychopharmacology
76:346-350, 1982 5. Van Putten T, Marder SR, Mintz J, Polant RE: Haloperidol plasma levels and
clinical response: a therapeutic window relationship. Am J Psychiatry 1992;149:500-505 6. Shostak M,
Perel JM, Stiller RL, et al: Plasma haloperidol and clinical response: a role for reduced haloperidol in
antipsychotic activity? J Clin Psychopharmacol 1987;7:394-400
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 985
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Reference Values:
Reference Range:
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 986
alpha-1-antitrypsin and C-reactive protein.
Reference Values:
30-200 mg/dL
Clinical References: 1. Silverman LM: Amino aicds and proteins. In Tietz Textbook of Clinical
Chemistry. Edited by NW Tietz. Philadelphia, WB Saunders Company, 1986, pp 519-618 2. Kanakoudi
F, Drossou V, Tzimouli V, et al: Serum concentrations of 10 acute-phase proteins in healthy term and
preterm infants from birth to age 6 months. Clin Chem 1995;41:605-608 3. Siemens Nephelometer II
Operations Instruction Manual. Siemens, Inc., Newark, DE
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 987
6 > or =100 Strongly positive Reference values
apply to all ages.
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity of
allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB Saunders
Company, New York, 2007, Part VI, pp 961-971
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 988
HDL-3 cholesterol: 22 - 35 mg/dL
Useful For: Screening potentially exposed workers for heavy metal toxicity in settings where a
24-hour collection is problematic
Interpretation: The reference intervals for this test are Occupational Safety and Health
Adminstration (OSHA) thresholds. The ordering physician will be contacted regarding any result
exceeding OSHA thresholds to determine the level of workplace exposure and follow-up action.
Arsenic results exceeding the OSHA threshold will be fractionated to confirm the presence of toxic
forms. Measurement of urine excretion rates either before or after chelation therapy has been used as an
indicator of lead exposure. However, blood lead analysis has the strongest correlation with toxicity.
Normally, the excretion of cadmium is proportional to creatinine. When renal damage has occurred,
cadmium excretion increases relative to creatinine. The correlation between the levels of mercury in the
urine and clinical symptoms is poor, but urinary mercury is the most reliable way to assess exposure to
inorganic mercury.
Reference Values:
ARSENIC/CREATININE
<50 mcg/g
MERCURY/CREATININE
<35 mcg/g
CADMIUM/CREATININE
<3.0 mcg/g
LEAD/CREATININE
<5 mcg/g
Clinical References: See individual test descriptions for: -ASCRU / Arsenic/Creatinine Ratio,
Random, Urine -PBCRU / Lead/Creatinine Ratio, Random, Urine -CDOM / Cadmium Occupational
Monitor, Urine -HGOM / Mercury Occupational Monitor, Urine
Reference Values:
ARSENIC
0-12 ng/mL
Reference values apply to all ages.
LEAD
All ages: 0.0-4.9 mcg/dL
Critical values
Pediatrics (< or =15 years): > or =20.0 mcg/dL
Adults (> or =16 years): > or =70.0 mcg/dL
CADMIUM
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0.0-4.9 ng/mL
Reference values apply to all ages.
MERCURY
0-9 ng/mL
Reference values apply to all ages.
Clinical References: Arsenic: Hall M, Chen Y, Ahsan H, et al: Blood arsenic as a biomarker of
arsenic exposure: results from a prospective study. Toxicology 2006;225:225-233 Lead: 1.
http://www.cdc.gov/exposurereport 2. de Burbure C, Buchet J-P, Leroyer A, et al: Renal and neurologic
effects of cadmium, lead, mercury, and arsenic in children: evidence of early effects and multiple
interactions at environmental exposure levels. Environ Health Perspect 2006;114:584-590 3. Kosnett MJ,
Wedeen RP, Rothenberg SJ, et al: Recommendations for medical management of adult lead exposure.
Environ Health Perspect 2007;115:463-471 4. Jusko T, Henderson C, Lanphear B, et al: Blood lead
concentrations <10 mcg/dL and child intelligence at 6 years of age. Environ Health Perspect
2008;116:243-248 Cadmium: Moreau T, Lellouch J, Juguet B, et al: Blood cadmium levels in a general
population with special reference to smoking. Arch Environ Health 1983;38:163-167 Mercury: 1. Lee R,
Middleton D, Calwell K, et al: A review of events that expose children to elemental mercury in the United
States. Environ Health Perspect 2009;117:871-878 2. Bjorkman L, Lundekvam B, Laegreid T, et al:
Mercury in human brain, blood, muscle and toenails in relation to exposure: an autopsy study.
Environmental Health 2007;6:30-44 3. deBurbure C, Buchet JP, Leroyer A, et al: Renal and neurologic
effects of cadmium, lead, mercury, and arsenic in children: evidence of early effects and multiple
interactions at environmental exposure levels. Environ Health Perspect 2006;114:584-590
Reference Values:
ARSENIC
0-35 mcg/specimen
Reference values apply to all ages.
LEAD
0-4 mcg/specimen
Reference values apply to all ages.
CADMIUM
0-15 years: not established
> or =16 years: 0.0-1.3 mcg/specimen
MERCURY
0-15 years: not established
> or =16 years: 0-9 mcg/specimen
Toxic concentration: >50 mcg/specimen
The concentration at which toxicity is expressed is widely variable between patients. 50 mcg/specimen is
the lowest concentration at which toxicity is usually apparent.
Reference Values:
ARSENIC
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0-35 mcg/L
Reference values apply to all ages.
LEAD
0-4 mcg/L
Reference values apply to all ages.
CADMIUM
0-15 years: not established
> or =16 years: 0.0-1.3 mcg/L
MERCURY
0-15 years: not established
> or =16 years: 0-9 mcg/L
Toxic concentration: >50 mcg/L
The concentration at which toxicity is expressed is widely variable between patients. 50 mcg/L is the
lowest concentration at which toxicity is usually apparent.
LEAD
0.0-3.9 mcg/g of hair
Reference values apply to all ages.
MERCURY
0-15 years: not established
> or =16 years: 0.0-0.9 mcg/g of hair
LEAD
0.0-3.9 mcg/g of nails
Reference values apply to all ages.
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MERCURY
0-15 years: not established
> or =16 years: 0.0-0.9 mcg/g of nails
Useful For: As an aid in the diagnosis of Helicobacter pylori Monitoring the eradication of
Helicobacter pylori after therapy (in most situations, confirmation of eradication is not mandatory) The
utility of this test in asymptomatic individuals is not known, but testing for Helicobacter pylori in such
individuals is not generally recommended
Interpretation: Positive results indicate the presence of Helicobacter pylori antigen in the stool.
Negative results indicate the absence of detectable antigen but does not eliminate the possibility of
infection due to Helicobacter pylori.
Reference Values:
Negative
Clinical References: 1. NIH Consensus Development Panel. Helicobacter pylori in peptic ulcer
disease. JAMA 1994;272:65-69 2. Report of the Digestive Health Initiative. International Update
Conference on H. pylori. Tysons Corner, McLean, VA, Feb 13-16, 1997
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 994
for diagnosing H pylori infection prior to antimicrobial treatment and for assessing whether the organism
has been successfully eradicated following antimicrobial therapy. In 2 recent large prospective studies, the
(13)C-UBT was shown to be as, or more, sensitive and specific for diagnosing H pylori active infection
than culture, PCR, stain, rapid urease testing of biopsy tissue, or serology. When the test is used to assess
eradication, it should be performed 4 to 6 weeks after completion of antimicrobial treatment. See
Helicobacter pylori Diagnostic Algorithm in Special Instructions.
Useful For: Diagnostic testing for Helicobacter pylori infection in patients suspected to have active
H pylori infection or for monitoring response to therapy
Interpretation: The Helicobacter pylori urea breath test can detect very low levels of H pylori and,
by assessing the entire gastric mucosa, avoids the risk of sampling errors inherent in biopsy-based
methods. In the absence of gastric H pylori, the (13)C-urea does not produce (13)CO2 in the stomach. A
negative result does not rule out the possibility of H pylori infection. If clinical signs are suggestive of
H pylori infection, retest with a new specimen or by using an alternative method. A false-positive test
may occur due to urease associated with other gastric spiral organisms observed in humans such as H
heilmannii. A false-positive test could occur in patients who have achlorhydria.
Reference Values:
Negative
Useful For: Recovery of Helicobacter pylori from gastric specimens for antimicrobial susceptibility
testing of the organism
Interpretation: A positive result provides definitive evidence of the presence of Helicobacter pylori.
Organisms may be detected in asymptomatic (colonized) individuals. False-negative culture results may
occur since the organism may die between biopsy collection and laboratory culture.
Reference Values:
No growth after 7 days
Clinical References: Theel ES: Helicobacter pylori Infection: Test Utilization Strategies for
Diagnosis. Mayo Medical Laboratories Communique 2013;38(6):1-8
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infection. Antimicrobial resistance in H pylori is increasing. Disease caused by H pylori resistant to
clarithromycin or metronidazole is associated with a greater incidence of treatment failure than disease
caused by a susceptible strain. The Clinical and Laboratory Standards Institute (CLSI) recommends agar
dilution for H pylori antimicrobial susceptibility testing. Amoxicillin, ciprofloxacin, clarithromycin,
metronidazole and tetracycline are routinely tested. The only antimicrobial for which interpretive
breakpoints have been defined by the CLSI is clarithromycin.
Useful For: Recovery of Helicobacter pylori from gastric specimens for antimicrobial susceptibility
testing of the organism (amoxicillin, ciprofloxacin, clarithromycin, metronidazole and tetracycline are
routinely tested)
Interpretation: A positive result provides definitive evidence of the presence of Helicobacter pylori.
Organisms may be detected in asymptomatic (colonized) individuals. False-negative culture results may
occur since the organism may die between biopsy collection and laboratory culture.
Reference Values:
No growth after 7 days
Susceptibility results are reported as minimum inhibitory concentration (MIC) in mcg/mL and as
susceptible, intermediate, or resistant according to the Clinical and Laboratory Standards Institute (CLSI)
guidelines.
In some instances an interpretive category cannot be provided based on available data and the following
comment will be included: "There are no established interpretive guidelines for agents reported without
interpretations."
Susceptible (S):
The "susceptible" category implies that isolates are inhibited by the usually achievable concentrations of
antimicrobial agent when the dosage recommended to treat the site of infection is used, resulting in likely
clinical efficacy.
Intermediate (I)
The "intermediate" category includes isolates with antimicrobial agent minimum inhibitory
concentrations (MICs) that approach usually attainable blood and tissue levels, and for which response
rates may be lower than for susceptible isolates.
Note: The intermediate category implies clinical efficacy in body sites where the drugs are
physiologically concentrated or when a higher than normal dosage of a drug can be used. This category
also includes a buffer zone, which should prevent small, uncontrolled, technical factors from causing
major discrepancies in interpretations, especially for drugs with narrow pharmacotoxicity margins.
Resistant (R)
The "resistant" category implies that the isolates are not inhibited by the usually achievable
concentrations of the agent with normal dosage schedules and/or that demonstrate MIC that fall in the
range where specific microbial resistance mechanisms are likely, and clinical efficacy of the agent against
the isolate has not been reliably shown in treatment studies.
(Clinical and Laboratory Standards Institute: Performance Standards for Antimicrobial Susceptibility
Testing. 26th Informational Supplement. CLSI document M100S. Wayne, PA, 2016)
Clinical References: Theel ES. Helicobacter pylori Infection: Test Utilization Strategies for
Diagnosis. Mayo Medical Laboratories Communique 2013;38(6):1-8
Useful For: Testing for IgE antibodies may be useful to establish the diagnosis of an allergic disease
and to define the allergens responsible for eliciting signs and symptoms. Testing also may be useful to
identify allergens which may be responsible for allergic disease and/or anaphylactic episode, to confirm
sensitization to particular allergens prior to beginning immunotherapy, and to investigate the specificity
of allergic reactions to insect venom allergens, drugs, or chemical allergens.
Reference Values:
Class IgE kU/L Interpretation
0 Negative
1 0.35-0.69 Equivocal
2 0.70-3.49 Positive
3 3.50-17.4 Positive
Clinical References: Homburger HA: Chapter 53: Allergic diseases. In Clinical Diagnosis and
Management by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. WB
Saunders Company, New York, 2007, Part VI, pp 961-971
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FHSSE Helminthosporium sativum/Drecshlera IgE
57532 Interpretation: Class IgG (kU/L) Comment 0 <0.35 Below Detection 1 0.35 0.69 Low Positive 2
0.70 3.49 Moderate Positive 3 3.50 17.49 Positive 4 17.50 49.99 Strong Positive 5 50.00
99.99 Very Strong Positive 6 >99.99 Very Strong Positive
Reference Values:
<0.35 kU/L
Useful For: Holding the bone marrow or peripheral blood specimen in the laboratory but delaying
chromosome analysis while preliminary morphologic assessment is in process
Interpretation: If notified by the client, this test may be canceled and a processing fee assessed. If no
notification to cancel testing is received, this test will be reported as "reflexed for chromosome analysis"
and depending on the specimen received, CHRBM / Chromosome Analysis, Hematologic Disorders,
Bone Marrow or CHRHB / Chromosome Analysis, Hematologic Disorders, Blood will be performed and
an interpretive report provided.
Reference Values:
Not applicable
Useful For: Reserving nucleic acid on any specimen for which molecular analysis requiring DNA or
RNA may be necessary at a future date, ensuring that adequate material for testing is available
Interpretation: A report of "Performed" will be sent and a $75 processing fee will be assessed. No
interpretation will be given. Should the sample be used in future testing, interpretation would be
incorporated with the final testing.
Reference Values:
Not applicable
Useful For: Reserving nucleic acid on any specimen for which molecular analysis requiring DNA
may be necessary at a future date, ensuring that adequate material for testing is available
Interpretation: A report of "Performed" will be sent and a $50 processing fee will be assessed. No
interpretation will be given. Should the sample be used in future testing, interpretation would be
incorporated with the final testing.
Reference Values:
Not applicable
Useful For: Processing the bone marrow or peripheral blood specimen but delaying FISH analysis
while preliminary morphologic assessment is in process
Interpretation: If notified by the client, this test may be canceled and a processing fee will be
assessed. If no notification to proceed with testing is received, this test will be reported as "canceled."
Reference Values:
Not applicable
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Interpretation: Report will include a morphologic description, a summary of the procedure, the
percent positivity of selected antigens, and an interpretive conclusion based on the correlation of the
clinical history with the morphologic features and immunophenotypic results.
Reference Values:
When performed, an interpretive report will be provided.
This test will be processed as a laboratory consultation. An interpretation of the immunophenotypic
findings and correlation with the morphologic features will be provided by a hematopathologist.
Clinical References: 1. Hanson CA, Kurtin PJ, Katzman JA, et al: Immunophenotypic analysis of
peripheral blood and bone marrow in the staging of B-cell malignant lymphoma. Blood
1999;94:3889-3896 2. Hanson CA: Acute leukemias and myelodysplastic syndromes. In Clinical
Laboratory Medicine. Edited by KD McClatchey. Baltimore, MD, Williams and Wilkins, Inc, 1994, pp
939-969 3. Morice WG, Leibson PJ, Tefferi A: Natural killer cells and the syndrome of chronic natural
killer cell lymphocytosis. Leuk Lymphoma 2001;41(3-4):277-284 4. Langerak AW, van Den Beemd R,
Wolvers-Tettero IL, et al: Molecular and flow cytometric analysis of the Vbeta repertoire for clonality
assessment in mature TCR alpha beta T-cell proliferations. Blood 2001;98(1):165-173 5. Hoffman RA,
Kung PC, Hansen QP, Goldstein G: Simple and rapid measurement of T-lymphocytes and their subclass
in peripheral blood. Proc Natl Acad Sci USA 1980;77:4914-4917 6. Jaffe ES, Cossman J:
Immunodiagnosis of lymphoid and mononuclear phagocytic neoplasms. In Manual of Clinical
Immunology. Third edition. Edited by NR Rose, H Friedman, JL Fahey JL. ASM Press, 1987, pp 779-790
7. Morice WG, Kimlinger T, Katzmann JA, et al: Flow cytometric assessment of TCR-V-beta expression
in the evaluation of peripheral blood involvement by T-cell lymphoproliferative disorders: a comparison
with conventional T-cell immunophenotyping and molecular genetic techniques. Am J Clin Pathol
2004;121(3):373-383 8. Stelzer GT, Shultz KE, Loken MR: CD45 gating for routine flow cytometric
analysis of bone marrow specimens. Ann NY Acad Sci 1993;677:265-280
Useful For: Evaluating chronic lymphocytic leukemia patients at diagnosis or during disease course for
the presence of TP53 gene mutations indicating high risk of disease progression and adverse outcome
Interpretation: The presence of TP53 gene mutations indicates a high risk of disease progression and
an adverse outcome. Results are reported in standard nomenclature according to the most recent Human
Genome Variation Society (HGVS) recommendations and an interpretive comment regarding the nature
of the mutation (eg, known deleterious, suspected deleterious, synonymous change) will be included to
complete the clinical report.
Reference Values:
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Mutations present or absent as compared to a reference sequence of the normal TP53 gene
Useful For: Obtaining a rapid, expert opinion on unprocessed specimens referred by the primary
pathologist Obtaining special studies not available locally
Interpretation: Results of the consultation are reported in a formal pathology report that includes a
description of ancillary test results (if applicable) and an interpretive comment. When the case is
completed, results may be communicated by a phone call. The formal pathology report is faxed. In our
consultative practice, we strive to bring the customer the highest quality of diagnostic pathology, in all
areas of expertise, aiming to utilize only those ancillary tests that support the diagnosis in a
cost-effective manner, and to provide a rapid turnaround time for diagnostic results.
Reference Values:
The laboratory will provide a pathology consultation.
Useful For: Establishing or confirming the clinical diagnosis of hereditary hemochromatosis (HH) in
adults HFE genetic testing is NOT recommended for population screening Testing of individuals with
increased transferrin-iron saturation in serum and serum ferritin With appropriate genetic counseling,
predictive testing of individuals who have a family history of HH
Interpretation: An interpretive report will be provided. For more information about hereditary
hemochromatosis testing, see Hereditary Hemochromatosis Algorithm in Special Instructions.
Reference Values:
An interpretative report will be provided.
Useful For: An aid in the identification of red blood cells and red blood cell precursors
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Interpretation: This test includes only technical performance of the stain (no pathologist
interpretation is performed). If diagnostic consultation by a pathologist is required order 70012 /
Pathology Consultation. The positive and negative controls are verified as showing appropriate
immunoreactivity. If a control tissue is not included on the slide, a scanned image of the relevant quality
control tissue is available upon request. Please contact 1-855-516-8404. Interpretation of this test should
be performed in the context of the patient's clinical history and other diagnostic tests by a qualified
pathologist.
Clinical References: 1. Chuang SS, Li CY: Useful panel of antibodies for the classification of
acute leukemia by immunohistochemical methods in bone marrow trephine biopsy specimens. Am J
Clin Pathol 1997;107(4):410-418 2. Dong HY, Wilkes S, Yang H: CD71 is selectively and ubiquitously
expressed at high levels in erythroid precursors of all maturation stages: A comparative
immunochemical study with glycophorin A and hemoglobin A. Am J Surg Pathol 2011;35(5): 723-732
3. OMalley DP, Young SK, Perkins SL, et al: Morphologic and immunohistochemical evaluation
of splenic hematopoietic proliferations in neoplastic and benign disorders. Modern Pathology
2005;18:1550-1561
Useful For: Evaluating the long-term control of blood glucose concentrations in diabetic patients
Diagnosing diabetes Identifying patients at increased risk for diabetes (prediabetes)
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HbA1c - Action suggested: >8.0% HbA1c -Pediatric patients: - Toddlers and preschoolers: <8.5% (but
>7.5%) - School age (6-12 years): <8% - Adolescents and young adults (13-19 years): <7.5% The ADA
recommendations for clinical practice suggest maintaining a HbA1c value closer to normal yields
improved microvascular outcomes for diabetics.(1) Target goals of <7% may be beneficial in patients
such as those with short duration of diabetes, long life expectancy, and no significant cardiovascular
disease. However, in patients with significant complications of diabetes, limited life expectancy, or
extensive comorbid conditions, targeting a <7% goal may not be appropriate. Since the HbA1c assay
reflects long-term fluctuations in blood glucose concentration, a diabetic patient who has in recent
weeks come under good control may still have a high concentration of HbA1c. The converse is true for
a diabetic previously under good control who is now poorly controlled. HbA1c results <4.0% are
reported with the comment: "Falsely low HbA1c results may be observed in patients with clinical
conditions that shorten erythrocyte life span or decrease mean erythrocyte age. HbA1c may not
accurately reflect glycemic control when clinical conditions that affect erythrocyte survival are present.
Fructosamine may be used as an alternate measurement of glycemic control."
Reference Values:
4.0-5.6%
<18 years: Hemoglobin A1c criteria for diagnosing diabetes have not been established for patients who
are <18 years of age.
> or =18 years: Increased risk for diabetes (prediabetes): 5.7-6.4%
Diabetes: > or =6.5%
Interpretive information based on Diagnosis and Classification of Diabetes Mellitus, American Diabetes
Association.
Clinical References: 1. Goldstein DE, Little RR, Lorenz RA, et al: Tests of glycemia in diabetes.
Diabetes Care 2003 Jan;26:S106-S108 2. Nathan DM, Kuenen J, Borg R, et al: Translating the A1c assay
into estimated average glucose values. Diabetes Care 2008 Aug;31:1473-1478 3. American Diabetes
Association, Position Statement, Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2014
Jan;37:S14-S80 4. Little RR, Wiedmeyer HM, England JD, et al: Interlaboratory standardization of
measurements of glycohemoglobins. Clin Chem 1992;38:2472-2478 5. Hoelzel W, Weykamp C,
Jeppsson JO, et al: IFCC reference system for measurement of hemoglobin A1c in human blood and the
national standardization schemes in the United States, Japan, and Sweden: a method-comparison study.
Clin Chem 2004;50(1):166-174
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Useful For: Diagnosis of thalassemias and hemoglobin variants Evaluation of unexplained
microcytosis
Interpretation: The types of hemoglobin present are identified, quantitated, and an interpretive
report is issued.
Reference Values:
HEMOGLOBIN A
1-30 days: 5.9-77.2%
1-2 months: 7.9-92.4%
3-5 months: 54.7-97.1%
6-8 months: 80.0-98.0%
9-12 months: 86.2-98.0%
13-17 months: 88.8-98.0%
18-23 months: 90.4-98.0%
> or =24 months: 95.8-98.0%
HEMOGLOBIN A2
1-30 days: 0.0-2.1%
1-2 months: 0.0-2.6%
3-5 months: 1.3-3.1%
> or =6 months: 2.0-3.3%
HEMOGLOBIN F
1-30 days: 22.8-92.0%
1-2 months: 7.6-89.8%
3-5 months: 1.6-42.2%
6-8 months: 0.0-16.7%
9-12 months: 0.0-10.5%
13-17 months: 0.0-7.9%
18-23 months: 0.0-6.3%
> or =24 months: 0.0-0.9%
VARIANT
No abnormal variants
VARIANT 2
No abnormal variants
VARIANT 3
No abnormal variants
Clinical References: Hoyer JD, Hoffman DR: The Thalassemia and hemoglobinopathy
syndromes. In Clinical Laboratory Medicine. Second edition. Edited by KD McMlatchey. Philadelphia,
Lippincott Williams and Wilkins, 2002, pp 866-895
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a discriminator between Diamond-Blackfan congenital pure red cell aplasia (elevated) and transient
erythroblastopenia of childhood (normal), but whether this simply reflects the chronicity of anemia
inherent to the former condition rather than a specific finding is unclear. In the common (large
deletional) form of the genetic trait hereditary persistence of HPFH, all of the erythrocytes contain Hb
F. When tested by flow cytometry using specificity for Hb F, these HPFH cases display a homocellular
distribution pattern of Hb F within the red cell population. Other causes of increased Hb F including
delta beta thalassemia, hydroxyurea, and some nondeletional HPFH mutations typically display a
heterocellular distribution of Hb F within the red cells, reflecting disparate populations of F cells and
cells lacking Hb F. Quantification of Hb F percentage should be determined prior to flow cytometry of
Hb F red cell distribution to establish the appropriateness of this test. The flow cytometry analysis of
elevated Hb F levels is useful when Hb F percentage is between 15% to 35% and the clinical differential
diagnosis includes large deletional HPFH. Hb F percentages below 15% are likely not due to large
deletional HPFH and causes of Hb F percentages above 35% are better confirmed by molecular and
family studies.
Useful For: Distinguishing large deletional hereditary persistence of fetal hemoglobin from other
conditions with increased percentage of fetal hemoglobin Determining the distribution of Hb F within red
blood cells
Reference Values:
Reported as heterocellular or homocellular
Useful For: Screening for presence or absence of hemoglobin S (sickle cell disease) Note: for
quantification of hemoglobin S order HBELC / Hemoglobin Electrophoresis Cascade, Blood
Reference Values:
Negative
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Clinical References: Fairbanks VF: Laboratory methods and case studies. In Hemoglobinopathies
and Thalassemias. Edited by BC Decker, New York, Thieme-Stratton Inc, 1980, pp 105-107
Useful For: Monitoring patients with sickling disorders who have received hydroxyurea or
transfusion therapy
Interpretation: Clinically, optimal levels of hemoglobin S (Hb S) and hemoglobin F (Hb F) are
patient specific and depend on a number of factors including response to therapy. This test will be
performed by capillary electrophoresis and any variant present will be reported as their zone only,
including Hb S. No confirmatory functional study such as sickle solubility will be performed.
Information reported: Percentages of hemoglobin A (Hb A), hemoglobin A2 (Hb A2), Hb F and any
variant present. Variants will be reported as zones and are not specific, even if present in Z5 (Zone S). If
the identity of the variant has not been previously confirmed, diagnostic hemoglobin electrophoresis is
necessary (see HBELC / Hemoglobin Electrophoresis Cascade, Blood).
Reference Values:
HEMOGLOBIN A
1-30 days: 5.9-77.2%
1-2 months: 7.9-92.4%
3-5 months: 54.7-97.1%
6-8 months: 80.0-98.0%
9-12 months: 86.2-98.0%
13-17 months: 88.8-98.0%
18-23 months: 90.4-98.0%
> or =24 months: 95.8-98.0%
HEMOGLOBIN A2
1-30 days: 0.0-2.1%
1-2 months: 0.0-2.6%
3-5 months: 1.3-3.1%
> or =6 months: 2.0-3.3%
HEMOGLOBIN F
1-30 days: 22.8-92.0%
1-2 months: 7.6-89.8%
3-5 months: 1.6-42.2%
6-8 months: 0.0-16.7%
9-12 months: 0.0-10.5%
13-17 months: 0.0-7.9%
18-23 months: 0.0-6.3%
> or =24 months: 0.0-0.9%
VARIANT 1
0.0
VARIANT 2
0.0
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VARIANT 3
0.0
Clinical References: 1. The Management of Sickle Cell Disease. Fourth edition. Bethesda, MD:
National Institutes of Health. National Heart, Lung, and Body Institute, 2002 2. Rosse WF, Telen M,
Ware R: Transfusion Support for Patients with Sickle Cell Disease. Bethesda, MD: American Association
of Blood Banks 1998 3. Ferster A, Tahriri P, Vermylen C, et al: Five years of experience with
hydroxyurea in children and young adults with sickle cell disease. Blood 2001;97:3268-3632 4. Charache
S, Terrin ML, Moore RD, et al: Effect of hydroxyurea on the frequency of painful crises in sickle cell
anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. N Engl J Med
1995;332:1317-1322 5. Sebia CapillaryS Manual: 2014(06) Available at
www.iproweb.fr/test/3%20-%20AU%20SOL/SEBIA%20-%20CAPILLARYS%202/MANUAL%202.pdf
6. Keren DF, Shalhoub R, Gulbranson R, et al: Expression of hemoglobin variant migration by capillary
electrophoresis relative to hemoglobin A2 improves precision. Am J Clin Pathol 2012
Apr;137(4):660-664
Reference Values:
Appearance (internal specimens only): normal
Hemoglobin: negative
RBCs (internal specimens only): 0-2 rbcs/hpf
Clinical References: Fairbanks, V.F. and Klee G.G., Textbook of Clinical Chemistry 1986, Chapter
15, p 1562
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disease, disseminated intravascular coagulation, and drug-induced HA. This consultative evaluation looks
for the cause of increased red cell destruction and includes testing for red cell membrane disorders, such
as hereditary spherocytosis, hemoglobinopathies, and red cell enzyme abnormalities. This panel is limited
in use in patients with a history of recent transfusion and should be ordered as remote a date from
transfusion as possible in those that are chronically transfused.
Useful For: Evaluation of lifelong or inherited hemolytic anemias, including red cell membrane
disorders, unstable or abnormal hemoglobin variants, and red cell enzyme disorders Cold agglutinin
disorders and autoimmune disorders should be excluded prior to testing. This evaluation is not suitable
for acquired causes of hemolysis.
Clinical References: 1. Steiner LA, Gallagher PG. Erythrocyte disorders in the perinatal period.
Semin Perinatol 2007 Aug;31(4):254-61. PMID: 17825683 2. Beutler E: Glucose-6-phosphate
dehydrogenase deficiency and other enzyme abnormalities. In Hematology. Fifth edition. Edited by E
Beutler, MA Lichtman, BS Coller, TJ Kipps. New York, McGraw-Hill Book Company, 1995, pp
564-581 3. Hoyer JD, Hoffman DR: The thalassemia and hemoglobinopathy syndromes. In Clinical
Laboratory Medicine. Second edition. Edited by KD McMlatchey. Philadelphia, Lippincott, Williams
and Wilkins, 2002, pp 866-895 4. King MJ, Garon L, Hoyer JD, Iolascon A, et al: International
Council for Standardization in Haematology. ICSH guidelines for the laboratory diagnosis of
nonimmune hereditary red cell membrane disorders. Int J Lab Hematol 2015 Jun;37(3):304-25. PMID:
25790109 5. Lux SE, IV: Anatomy of the red cell membrane skeleton: unanswered questions. Blood
2016 Jan 14;127(2):187-99 DOI: 10.1182/blood-2014-12-512772. PMID: 26537302 6. Gallagher PG.
Abnormalities of the erythrocyte membrane. Pediatr Clin North Am 2013 Dec;60(6):1349-62. PMID:
24237975 7. Bianchi P, Fermo E, Vercellati C, Marcello AP, et al: Diagnostic power of laboratory tests
for hereditary spherocytosis: a comparison study in 150 patients grouped according to molecular and
clinical characteristics. Haematologica 2012 Apr;97(4):516-23. PMID: 22058213 8. Cappellini MD,
Fiorelli G. Glucose-6-phosphate dehydrogenase deficiency. Lancet 2008;371:64-74 9. Hereditary
hemolytic anemias due to red blood cell enzyme disorders. Edited by B Glader. Philadelphia: Wolters
Kluwer/Lippincott, Williams and Wilkins; 2014, pp 728
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 1009
mothers of isolated cases do not have an identifiable germline F8 mutation. Importantly, there is a small
risk for recurrence even when the familial F8 mutation is not identified in the mother of the affected
patient due to the possibility of germline mosaicism.
Useful For: Prenatal testing for hemophilia A when a mutation has not been identified in the family.
Interpretation: An interpretive report will be provided.
Reference Values:
Not applicable
Clinical References: 1. Antonarakis SE, Rossiter JP, Young M, et al: Factor VIII gene inversions in
severe hemophilia A: results of an international consortium study. Blood 1995;86(6):2206-2212 2.
Rossiter JP, Young M, Kimberland ML, et al: Factor VIII gene inversions causing severe hemophilia A
originate almost exclusively in male germ cells. Hum Mol Genet 1994;3(7):1035-1039 3. Castaldo G,
D'Argenio V, Nardiello P, et al: Haemophilia A: molecular insights. Clin Chem Lab Med
2007;45(4):450-461 4. Oldenburg J, Rost S, El-Maarri O, et al: De novo factor VIII gene intron 22
inversion in a female carrier presents as a somatic mosaicism. Blood 2000;96(8):2905-2906 5. Pruthi RK:
Hemophilia: A Practical Approach to Genetic Testing. Mayo Clin Proc 2005;80:1485-1499
Useful For: First-tier molecular testing for males affected with severe hemophilia A when a mutation
has not been identified in the family. Determining hemophilia A carrier status for at-risk females, ie,
individuals with a family history of severe hemophilia A
Clinical References: 1. Antonarakis SE, Rossiter JP, Young M, et al: Factor VIII gene inversions in
severe hemophilia A: results of an international consortium study. Blood 1995;86(6):2206-2212 2.
Rossiter JP, Young M, Kimberland ML, et al: Factor VIII gene inversions causing severe hemophilia A
originate almost exclusively in male germ cells. Hum Mol Genet 1994;3(7):1035-1039 3. Castaldo G,
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 1010
D'Argenio V, Nardiello P, et al: Haemophilia A: molecular insights. Clin Chem Lab Med
2007;45(4):450-461 4. Oldenburg J, Rost S, El-Maarri O, et al: De novo factor VIII gene intron 22
inversion in a female carrier presents as a somatic mosaicism. Blood 2000;96(8):2905-2906 5. Pruthi RK:
Hemophilia: A Practical Approach to Genetic Testing. Mayo Clin Proc 2005;80:1485-1499
Useful For: Prenatal testing for hemophilia A when a F8 intron 1 inversion has been identified in a
family member.
Clinical References: 1. Antonarakis SE, Rossiter JP, Young M, et al: Factor VIII gene inversions
in severe hemophilia A: results of an international consortium study. Blood 1995;86(6):2206-2212 2.
Rossiter JP, Young M, Kimberland ML, et al: Factor VIII gene inversions causing severe hemophilia A
originate almost exclusively in male germ cells. Hum Mol Genet 1994;3(7):1035-1039 3. Castaldo G,
D'Argenio V, Nardiello P, et al: Haemophilia A: molecular insights. Clin Chem Lab Med
2007;45(4):450-461 4. Pruthi RK: Hemophilia: A Practical Approach to Genetic Testing. Mayo Clin
Proc 2005;80:1485-1499
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 1011
associated with severe disease, 1% to 5% activity with moderate disease, and 5% to 40% with mild
disease. In males with severe deficiency, spontaneous bleeding may occur. In individuals with mild HA,
bleeding may occur only after surgery or trauma. FVIII is encoded by the factor VIII (F8) gene.
Approximately 98% of patients with a diagnosis of HA are found to have a mutation in F8 (ie, intron 1
and 22 inversions, point mutations, insertions, and deletions). The intron 1 inversion mutation accounts
for approximately 5% of mutations associated with severe HA. These inversions are typically not
identified in patients with mild or moderate HA. Intron 1 inversion known mutation analysis is only
recommended for individuals when an intron 1 inversion has already been identified in the family. If a
familial mutation has not been identified in a severely affected HA patient the F8 gene intron 1 and 22
inversion analysis (F8INV / Hemophilia A F8 Gene, Intron 1 and 22 Inversion Mutation Analysis,
Whole Blood) should be ordered. If the intron 1 inversion analysis is negative, the tested individual has
not inherited the familial mutation. It is recommended that the F8 mutation be confirmed in the affected
male or obligate carrier female prior to testing at-risk individuals. Affected males are identified by
FVIII activity (F8A / Coagulation Factor VIII Activity Assay, Plasma) and clinical evaluation, while
obligate carrier females are identified by family history assessment. If the intron inversion assays do not
detect an inversion in these individuals, additional analysis (ie, F8 sequencing) may be able to identify
the familial mutation. Of note, not all females with an affected son are germline carriers of a F8
mutation, as de novo mutations in F8 do occur. Approximately 20% of mothers of isolated cases do not
have an identifiable germline F8 mutation. Importantly, there is a small risk for recurrence even when
the familial F8 mutation is not identified in the mother of the affected patient due to the possibility of
germline mosaicism.
Useful For: First-tier molecular testing for males affected with severe hemophilia A, when a familial
intron 1 inversion has been previously identified. Determining hemophilia A carrier status for at-risk
females, ie, individuals with a family history of severe hemophilia A due to F8 intron 1 inversion
Clinical References: 1. Antonarakis SE, Rossiter JP, Young M, et al: Factor VIII gene inversions in
severe hemophilia A: results of an international consortium study. Blood 1995;86(6):2206-2212 2.
Rossiter JP, Young M, Kimberland ML, et al: Factor VIII gene inversions causing severe hemophilia A
originate almost exclusively in male germ cells. Hum Mol Genet 1994;3(7):1035-1039 3. Castaldo G,
D'Argenio V, Nardiello P, et al: Haemophilia A: molecular insights. Clin Chem Lab Med
2007;45(4):450-461 4. Pruthi RK: Hemophilia: A Practical Approach to Genetic Testing. Mayo Clin Proc
2005;80:1485-1499
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 1012
inversion analysis (F8INV / Hemophilia A F8 Gene, Intron 1 and 22 Inversion Mutation Analysis, Whole
Blood) should be ordered. If the intron 22 inversion analysis is negative, the tested individual has not
inherited the familial mutation. It is recommended that the F8 mutation be confirmed in the affected male
or obligate carrier female prior to testing at-risk individuals. Affected males are identified by FVIII
activity (F8A / Coagulation Factor VIII Activity Assay, Plasma) and clinical evaluation, while obligate
carrier females are identified by family history assessment. If the intron inversion assays do not detect an
inversion in these individuals, additional analysis (ie, F8 sequencing) may be able to identify the familial
mutation. Of note, not all females with an affected son are germline carriers of a F8 mutation, as de novo
mutations in F8 do occur. Approximately 20% of mothers of isolated cases do not have an identifiable
germline F8 mutation. Importantly, there is a small risk for recurrence even when the familial F8 mutation
is not identified in the mother of the affected patient due to the possibility of germline mosaicism.
Useful For: First-tier molecular testing for males affected with severe hemophilia A, when a familial
intron 22 inversion has been previously identified. Determining hemophilia A carrier status for at-risk
females, ie, individuals with a family history of severe hemophilia A due to F8 intron 22 inversion
Clinical References: 1. Antonarakis SE, Rossiter JP, Young M, et al: Factor VIII gene inversions
in severe hemophilia A: results of an international consortium study. Blood 1995;86(6):2206-2212 2.
Rossiter JP, Young M, Kimberland ML, et al: Factor VIII gene inversions causing severe hemophilia A
originate almost exclusively in male germ cells. Hum Mol Genet 1994;3(7):1035-1039 3. Castaldo G,
D'Argenio V, Nardiello P, et al: Haemophilia A: molecular insights. Clin Chem Lab Med
2007;45(4):450-461 4. Oldenburg J, Rost S, El-Maarri O, et al: De novo factor VIII gene intron 22
inversion in a female carrier presents as a somatic mosaicism. Blood 2000;96(8):2905-2906 5. Pruthi
RK: Hemophilia: A Practical Approach to Genetic Testing. Mayo Clin Proc 2005;80:1485-1499
Useful For: Prenatal testing for hemophilia A when a F8 intron 22 inversion has been identified in a
family member.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 1013
Interpretation: An interpretive report will be provided.
Reference Values:
Not applicable
Clinical References: 1. Antonarakis SE, Rossiter JP, Young M, et al: Factor VIII gene inversions in
severe hemophilia A: results of an international consortium study. Blood 1995;86(6):2206-2212 2.
Rossiter JP, Young M, Kimberland ML, et al: Factor VIII gene inversions causing severe hemophilia A
originate almost exclusively in male germ cells. Hum Mol Genet 1994;3(7):1035-1039 3. Castaldo G,
D'Argenio V, Nardiello P, et al: Haemophilia A: molecular insights. Clin Chem Lab Med
2007;45(4):450-461 4. Oldenburg J, Rost S, El-Maarri O, et al: De novo factor VIII gene intron 22
inversion in a female carrier presents as a somatic mosaicism. Blood 2000;96(8):2905-2906 5. Pruthi RK:
Hemophilia: A Practical Approach to Genetic Testing. Mayo Clin Proc 2005;80:1485-1499
Useful For: Prenatal testing for a known familial pathogenic mutation in the F9 gene in a fetus who is
at risk for inheriting this mutation
Clinical References: 1. Yoshitake S, Schach BG, Foster DC, et al: Complete nucleotide sequence of
the gene for human factor IX (antihemophilic factor B). Biochemistry 1985;24(14):3736-3750 2.
Giannelli F, Green PM, Sommer SS, et al: Haemophilia B: database of point mutations and short
additions and deletions-eighth edition. Nucleic Acids Res 1998;26(1):265-268 3. Ketterling RP, Bottema
CD, Phillips JA 3rd, Sommer SS: Evidence that descendants of three founders constitute about 25% of
hemophilia B in the United States. Genomics 1991;10(4):1093-1096
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 1014
mutation rate in the F9 gene (ie, de novo mutations). Hemophilia B affects males; however, all male
offspring from an affected male will be normal. Although all female offspring of affected males will be
obligatory carriers, they rarely have symptomatic bleeding. In contrast, female offspring of female carriers
of hemophilia B have a 50% chance of being carriers themselves, and each male offspring has a 50%
chance of being affected. Based on factor IX activity, hemophilia B is classified as severe (factor IX
activity <1%), moderate (factor IX activity 1%-5%), or mild (factor IX activity >5%-40%). In males, low
factor IX activity level establishes the diagnosis of hemophilia B. However, the wide range of normal
factor IX activity precludes an accurate assessment of carrier status in females, thus making molecular
testing essential in assessment of carrier status. Inhibitors to factor IX activity are estimated to occur in
5% to 8% of patients, much less than that of hemophilia A. Inhibitor risk correlates with genotype and
typically occurs in patients with either partial or total deletions of the F9 gene or in certain nonsense
mutations that result in no circulating factor IX antigen. More recently, it has been observed that a subset
of patients with such mutations may be at risk of experiencing anaphylactic reactions to the factor IX
replacement therapy.
Useful For: Diagnostic, targeted testing for hemophilia B when a mutation has been identified in a
family member Carrier testing of females in whom the familial F9 genotype is known
Clinical References: 1. Yoshitake S, Schach BG, Foster DC, et al: Nucleotide sequence of the
gene for human factor IX (antihemophilic factor B). Biochemistry 1985 July 2;24(14):3736-3750 2.
Giannelli F, Green PM, Sommer SS, et al: Haemophilia B: database of point mutations and short
additions and deletions. Eighth edition. Nucleic Acids Res 1998 Jan 1;26(1):265-268 3. Ketterling RP,
Bottema CD, Phillips JA 3rd, et al: Evidence that descendants of three founders constitute about 25% of
hemophilia B in the United States. Genomics 1991 Aug;10(4):1093-1096
Useful For: Prenatal testing for a pathogenic mutation in the F9 gene in a fetus with a strong,
confirmed family history of congenital hemophilia B (factor IX activity deficiency) in the exceptional
circumstance where a familial mutation cannot be otherwise ascertained
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 1015
An interpretive report will be issued that will include specimen information, assay information,
background information, and conclusions based on the test results (ie, information about the mutation
and carrier status).
Clinical References: 1. Yoshitake S, Schach BG, Foster DC, et al: Complete nucleotide sequence of
the gene for human factor IX (antihemophilic factor B). Biochemistry 1985;24(14):3736-3750 2.
Giannelli F, Green PM, Sommer SS, et al: Haemophilia B: database of point mutations and short
additions and deletions-eighth edition. Nucleic Acids Res 1998;26(1):265-268 3. Ketterling RP, Bottema
CD, Phillips JA 3rd, Sommer SS: Evidence that descendants of three founders constitute about 25% of
hemophilia B in the United States. Genomics 1991;10(4):1093-1096
Useful For: Ascertaining the causative mutation in the F9 gene of patients with congenital hemophilia
B (factor IX activity deficiency) Carrier testing of females in whom the familial F9 genotype is unknown
Interpretation: An interpretive report will be issued which will include specimen information, assay
information, background information, and conclusions based on the test results (ie, information about the
mutation and carrier status).
Reference Values:
Not applicable
Clinical References: 1. Yoshitake S, Schach BG, Foster DC, et al: Nucleotide sequence of the gene
for human factor IX (antihemophilic factor B). Biochemistry 1985 July 2;24(14):3736-3750 2. Giannelli
F, Green PM, Sommer SS, et al: Haemophilia B: database of point mutations and short additions and
deletions. Eighth edition. Nucleic Acids Res 1998 Jan 1;26(1):265-268 3. Ketterling RP, Bottema CD,
Phillips JA 3rd, et al: Evidence that descendants of three founders constitute about 25% of hemophilia B
in the United States. Genomics 1991 Aug;10(4):1093-1096
HQ HemoQuant, Feces
9220 Clinical Information: Several noninvasive tests are available to detect gastrointestinal (GI) bleeding.
However, guaiac type and immunochemical tests for occult bleeding are affected by the presence of
reducing or oxidizing substances and are insensitive for the detection of proximal gut bleeding, where
most clinically significant occult GI bleeding occurs. The HemoQuant test is the most reliable,
noninvasive test currently available for detecting bleeding of the esophago-GI tract. Unlike other tests for
blood in feces, this test detects both intact heme and porphyrins from partly degraded heme. Additionally,
test results are not complicated by either the water content of the specimen or the presence of reducing or
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 1016
oxidizing substances. Furthermore, HemoQuant testing is sensitive to both proximal and distal sources of
occult GI bleeding.
Useful For: Detection of blood in feces HemoQuant is the most appropriate fecal occult blood test to
use in the evaluation of iron deficiency Other useful applications include the detection of bleeding as a
complication of anticoagulant therapy and other medication regimens
Interpretation: Elevated levels are an indicator of the presence of blood in the feces, either from
benign or malignant causes. This test is not specific for bowel cancer.
Reference Values:
Normal:
< or =2.0 mg total hemoglobin/g feces
Marginal:
2.0-3.0 mg total hemoglobin/g feces
2.0-4.0 mg total hemoglobin/g feces*
Elevated:
>3.0 mg total hemoglobin/g feces
>4.0 mg total hemoglobin/g feces*
*Alternative reference values for persons who have ingested red meat or aspirin during any of the 3
days preceding specimen collection.
Clinical References: 1. Ahlquist DA, McGill DB, Schwartz S, et al: HemoQuant, a new
quantitative assay for fecal hemoglobin: comparison with Hemoccult. Ann Intern Med
1984;101:297-302 2. Ahlquist DA, Wieand HS, Moertel CG, et al: Accuracy of fecal occult blood
screening for colorectal neoplasia: a prospective study using Hemoccult and HemoQuant tests. JAMA
1993;269:1262-1267 3. Harewood GC, McConnell JP, Harrington JJ, et al: Detection of occult upper
gastrointestinal bleeding: performance differences in fecal blood tests. Mayo Clin Proc
2002;77(1):23-28
Interpretation: A positive hemosiderin indicates excess red cell destruction. Hemosiderinuria may
still be detected after hemoglobin has cleared from the urine and hemoglobin dipstick is negative.
Reference Values:
Hemosiderin: negative (reported as positive or negative)
Hemoglobin (internal specimens only): negative
RBC (internal specimens only): 0-2 rbc/hpf
Clinical References: Henry JB: Clinical Diagnosis and Management by Laboratory Methods. 18th
edition. Philadelphia, WB Saunders Company, 1991, pp 412-413
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 1017
99.99 Very Strong Positive 6 >99.99 Very Strong Positive
Reference Values:
<0.35 kU/L
Useful For: Measuring heparin concentration: -In patients treated with low-molecular-weight heparin
preparations -In presence of prolonged baseline activated partial thromboplastin time (APTT) (eg, lupus
anticoagulant, "contact factor" deficiency, etc) -When unfractionated heparin dose needed to achieve
desired APTT prolongation is unexpectedly higher (>50%) than expected
Clinical References: 1. Marci CD, Prager D: A review of the clinical indications for the plasma
heparin assay. Am J Clin Pathol 1993;99:546-550 2. Houbouyan L, Boutiere B, Contant G, et al:
Validation of analytical hemostasis systems: measurement of anti-Xa activity of
low-molecular-weight-heparins. Clin Chem 1996;42:1223-1230 3. Jeske W, Messmore HL Jr, Fareed J:
Pharmacology of heparin and oral anticoagulants. In Thrombosis and Hemorrhage. Second edition. Edited
by J Loscalzo, AI Schafer. Baltimore, MA, Williams and Wilkins, 1998, pp 1193-1204 4. Monagle P,
Michelson AD, Bovill E, Andrew M: Antithrombotic therapy in children. Chest 2001;119:344-370 5.
Fraser G, McKenna J: Monitoring low molecular weight heparins with antiXa activity: house of cards or
firm foundation? Hospital Pharmacy 2003;38:202-211 6. Nutescu EA, Spinler SA, Wittkowsky A, Dager
WE: Low-molecular-weight heparins in renal impairment and obesity: available evidence and clinical
practice recommendations across medical and surgical settings. Ann Pharmacother 2009;43:1064:1083
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 1018
FHPCF Heparin Cofactor II
91658 Reference Values:
65 - 145%
Interpretation: Results are reported as: 1) Reactivity (%); 2) Heparin inhibition (%); 3) Interpretation.
Typical patterns of results and interpretations are depicted in the following table. Interpretive comments
will also accompany test reports, when indicated. Reactivity (%) Heparin Inhibition (%) Interpretation
Normal Range <20 Not done Negative Positive >40 >50 Positive Equivocal 20-40 >50 Equivocal
Equivocal 20-40 < or =50 Equivocal Equivocal >40 < or =50 Equivocal A negative result of testing for
human platelet factor 4 (H/PF4) antibodies has about a 90% negative predictive value for exclusion of
clinical type II heparin-induced thrombocytopenia (HIT-II). Because up to 10% of patients with clinical
heparin-induced thrombocytopenia (HIT) may have a negative H/PF4 antibody enzyme-linked
immunosorbent assay (ELISA) result, a negative H/PF4 antibody ELISA result does not exclude the
diagnosis of HIT when clinical suspicion remains high. A functional assay for HIT antibodies (eg,
heparin-dependent platelet aggregation or serotonin release assay may be helpful in these circumstances).
Contact Mayo Medical Laboratories for ordering information. A positive result is indicative of the
presence of H/PF4 complex antibodies. However, this test's specificity is as low as 20% to 50% for
clinical diagnosis of HIT, depending on the patient population studied. For example, up to 50% of
surgical patients and up to 20% of medical patients treated with heparin may develop H/PF4 antibodies as
measured by ELISA, and only a small proportion (1%-5%) develop clinical HIT. Accordingly, this test
does not confirm the diagnosis of HIT-II. The diagnosis must be made in conjunction with clinical
findings, including evaluation for other potential causes of thrombocytopenia. The presence of H/PF4
antibodies likely increases the risk of clinical HIT, with risk probably partly dependent on associated
medical and surgical conditions, but currently there are few data about relative risk of HIT in various
populations with positive tests for H/PF4 antibodies.
Reference Values:
<20%
Reference Values:
Negative
Useful For: Detect and quantify Hepatitis A Virus DNA (HAV DNA).
Interpretation: The presence of target-specific nucleic acid is indicative of infection. Mean
Detection: 24.98 copies/mL (12.81 IU/mL) 95% Detection Cutoff: 61.83 copies/mL (31.71 IU/mL)
Reference Values:
Negative
Reference Values:
Negative
Clinical References: 1. Roque-Afonso AM, Desbois D, Dussaix E: Hepatitis A virus: serology and
molecular diagnostics. Future Virology 2010;5(2):233-242 2. De Paula VS: Laboratory diagnosis of
hepatitis A. Future Virology 2012;7(5):461-472 3. Wasley A, Fiore A, Bell BP: Hepatitis A in the era of
vaccination. Epidemiol Rev 2006;28:101-111 4. Nainan OV, Xia G, Vaughan G, Margolis HS: Diagnosis
of hepatitis A infection: a molecular approach. Clin Microbiol Rev 2006;19:63-79
Useful For: Detection and differentiation between acute/recent and past/resolved hepatitis A
Verification of immunity to hepatitis A
Interpretation: A positive antihepatitis A virus (anti-HAV) total (both IgG and IgM) result indicates
acute, recent, past/resolved exposure to hepatitis A, or immunity to hepatitis A from vaccination. Testing
for anti-HAV IgM (HAVM / Hepatitis A IgM Antibody, Serum) is necessary to confirm the presence of
acute or recent hepatitis A. A positive anti-HAV total result with a negative anti-HAV IgM result
indicates immunity to hepatitis A from either past or resolved hepatitis A or vaccination against hepatitis
A. Negative results indicate the absence of recent or past hepatitis A or a lack of immunity to HAV
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 1022
infection. Borderline test results for anti-HAV total may be seen in: 1) acute hepatitis A with rising levels
of anti-HAV IgM, 2) recent hepatitis with rising levels of anti-HAV IgG, or 3) cross-reactivity with
nonspecific antibodies (ie, false-positive results). Retesting of both anti-HAV total and anti-HAV IgM
(HAVM / Hepatitis A IgM Antibody, Serum) is recommended to determine the definitive HAV infection
status.
Reference Values:
Negative
See Viral Hepatitis Serologic Profiles in Special Instructions.
Useful For: An aid in the identification of hepatitis B infection (chronic active state)
Interpretation: This test includes only technical performance of the stain (no pathologist
interpretation is performed). If diagnostic consultation by a pathologist is required order 70012 /
Pathology Consultation. The positive and negative controls are verified as showing appropriate
immunoreactivity. If a control tissue is not included on the slide, a scanned image of the relevant quality
control tissue is available upon request. Please contact 1-855-516-8404. Interpretation of this test should
be performed in the context of the patient's clinical history and other diagnostic tests by a qualified
pathologist.
Clinical References: 1. Bonino F, Pratvisuth T, Brunetto MR, Liaw YF: Diagnostic markers of
chronic hepatitis B infection and disease. Antiviral therapy 2010;15(Suppl 3):35-44 2. Diniz G, Aktas S,
Ortac R, et al: A comparative immunohistochemical study of HBsAg, HBcAg and CD57 in chronic
hepatitis B pediatric patients with and without malignant disorders. Turk J Gastroenterol
2003;14(4):234-238 3. Gerber MA, Thung SN: The diagnostic value of immunohistochemical
demonstration of hepatitis viral antigens in the liver. Human Pathology 1987;18(8):771-774 4.
Sanchez-Quijano A, Jaurequi JI, Leal M, et al: Hepatitis B virus occult infection in subjects with
persistent isolated anti-HBc reactivity. Journal of Hepatology 1993;17(3):288-293 5. Sharma RR,
Dhiman RK, Chawia Y, Vasistha RK: Immunohistochemistry for core and surface antigens in chronic
hepatitis. Trop Gastroenterol 2002;23(1):16-19
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 1023
Special Instructions and The Laboratory Approach to the Diagnosis and Monitoring of Hepatitis B
Infection in Publications.
Useful For: Diagnosis of acute hepatitis B infection Identifying acute hepatitis B virus (HBV) infection
in the serologic window period when hepatitis B surface antigen (HBsAg) and antihepatitis B surface
(anti-HBs) are negative Differentiation between acute and chronic or past hepatitis B infection in the
presence of positive antihepatitis B core.
Interpretation: A positive result indicates recent acute hepatitis B infection. A negative result suggests
lack of recent exposure to the virus in preceding 6 months.
Reference Values:
Negative
Clinical References: 1. Bonino F. Piratvisuth T, Brunetto MR, et al: Diagnostic markers of chronic
hepatitis B infection and disease. Antiviral Therapy 2010;15(Suppl. 3):35-44 2. Badur S, Akgun A:
Diagnosis of hepatitis B infections and monitoring of treatment. J Clin Virol 2001;21:229-237 3. Servoss
JC, Friedman LS: Serologic and molecular diagnosis of hepatitis B virus. Clin Liver Dis 2004;8:267-281
Useful For: Diagnosis of recent or past hepatitis B infection Determination of occult hepatitis B
infection in otherwise healthy hepatitis B virus (HBV) carriers with negative test results for hepatitis B
surface antigen, antihepatitis B surface, antihepatitis B core IgM, hepatitis Be antigen, and anti-HBe. This
assay is not useful for differentiating among acute, chronic, and past/resolved hepatitis B infection. This
assay is FDA-approved for in vitro diagnostic use and not for screening cell, tissue, and blood donors.
Useful For: Detection and differentiation between recent and past/resolved or chronic hepatitis B
viral (HBV) infection Diagnosis of recent HBV infection during the "window period" when both
hepatitis B surface antigen and antibodies to hepatitis B surface antigen are negative
Interpretation: A positive, antibodies to hepatitis B core antigen (anti-HBc) total result may
indicate, either, recent, past/resolved, or chronic hepatitis B viral (HBV) infection. Testing for anti-HBc
IgM (HBIM / Hepatitis B Core Antibody IgM, Serum) is necessary to confirm the presence of acute or
recent hepatitis B. A positive anti-HBc total result with a negative anti-HBc IgM result indicates past or
chronic HBV infection. Differentiation between past/resolved and chronic hepatitis B can be based on
the presence of hepatitis B surface antigen in the latter condition. Negative anti-HBc total results
indicate the absence of recent, past/resolved, or chronic hepatitis B.
Reference Values:
Negative
Interpretation depends on clinical setting. See Viral Hepatitis Serologic Profiles in Special Instructions.
Useful For: Determining infectivity of hepatitis B virus (HBV) carriers Monitoring infection status
of chronically HBV-infected patients Monitoring serologic response of chronically HBV-infected
patients who are receiving antiviral therapy
Reference Values:
Negative
See Viral Hepatitis Serologic Profiles in Special Instructions.
Useful For: Determining infectivity of hepatitis B virus (HBV) carriers Monitoring infection status of
chronically HBV-infected patients Monitoring serologic response of chronically HBV-infected patients
receiving antiviral therapy
Interpretation: Presence of hepatitis B envelope (HBe) antigen and absence of HBe antibody usually
indicate active hepatitis B virus (HBV) replication and high infectivity. Absence of HBe antigen with
appearance of HBe antibody is consistent with loss of HBV infectivity. Although resolution of chronic
HBV infection generally follows appearance of HBe antibody, the HBV carrier state may persist.
Reference Values:
HEPATITIS BE ANTIGEN
Negative
HEPATITIS BE ANTIBODY
Negative
See Viral Hepatitis Serologic Profiles in Special Instructions.
Clinical References: 1. Bonino F, Piratvisuth T, Brunetto MR, et al: Diagnostic markers of chronic
hepatitis B infection and disease. Antiviral Therapy 2010;15(3):35-44 2. Servoss JC, Friedman LS:
Serologic and molecular diagnosis of hepatitis B virus. Clin Liver Dis 2004;8:267-281 3. Badur S, Akgun
A: Diagnosis of hepatitis B infections and monitoring of treatment. J Clin Virol 2001 Jun;21(3):229-237
Useful For: Determining infectivity of hepatitis B virus (HBV) carriers Monitoring infection status of
chronically HBV-infected patients Monitoring serologic response of chronically HBV-infected patients
who are receiving antiviral therapy
Interpretation: Presence of hepatitis Be (HBe) antigen and absence of HBe antibody usually indicate
active hepatitis B virus (HBV) replication and high infectivity. Absence of HBe antigen with appearance
of HBe antibody is consistent with resolution of HBV infectivity.
Reference Values:
Negative
See Viral Hepatitis Serologic Profiles in Special Instructions.
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 1026
Clinical References: 1. Bonino F, Piratvisuth T, Brunetto MR, et al: Diagnostic markers of
chronic hepatitis B infection and disease. Antiviral Therapy 2010;15(3):35-44 2. Servoss JC, Friedman
LS: Serologic and molecular diagnosis of hepatitis B virus. Clin Liver Dis 2004;8:267-281 3. Badur S,
Akgun A: Diagnosis of hepatitis B infections and monitoring of treatment. J Clin Virol 2001
Jun;21(3):229-237
Useful For: Determining hepatitis B virus infection and immunity status in infants born to mothers
with chronic hepatitis B and after receiving perinatal prophylaxis
Interpretation: Hepatitis B surface antigen (HBsAg) is the first serologic marker appearing in blood
at 6 to 16 weeks after exposure to HBV. A confirmed positive HBsAg result is indicative of acute or
chronic hepatitis B. In acute cases, HBsAg usually disappears 1 to 2 months after the onset of
symptoms. Persistence of HBsAg for >6-month duration indicates development of either a chronic
carrier state or chronic hepatitis B. Hepatitis B surface (HBs) antibody appears with the resolution of
HBV infection and disappearance of HBsAg. A positive result indicates recovery from acute or chronic
hepatitis B, or acquired immunity from HBV vaccination. This assay does not differentiate between a
vaccine-induced immune response and recovery from HBV infection. Positive results (HBs Ab levels of
>10.0 mIU/mL) indicate adequate immunity to hepatitis B. After receiving a primary HBV vaccine
series, individuals with HBs Ab levels of > or =10 mIU/mL are considered protected from hepatitis B in
accordance with the CDC guideline (CDC. Immunization of health-care personnel. MMWR
2011;60[No. SS-7]:5). A negative result (HBs levels of <10.0 mIU/mL) indicates a lack of recovery
from acute or chronic hepatitis B or inadequate immune response to HBV vaccination. Hepatitis B core
(HBc) total antibodies (combined IgG and IgM) appear shortly after the onset of symptoms of HBV
infection and may be the only serologic marker remaining years after exposure to HBV. A positive
result indicates exposure to HBV infection. A positive HBs antibody result along with a positive HBc
total antibody result is indicative of recovery from HBV infection. A positive HBs antibody result with
a negative HBc total antibody result is consistent with immunity to hepatitis B from HBV vaccination.
See Viral Hepatitis Serologic Profiles in Special Instructions.
Reference Values:
Negative
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 1027
HBABT Hepatitis B Surface Antibody Monitor, Post-Transplant, Serum
87893 Clinical Information: For patients with chronic hepatitis B virus (HBV) infection (hepatitis B surface
antigen-positive), outcomes following liver transplantation for end-stage liver disease are poor. Recurrent
HBV disease is common and associated with decreased liver graft and patient survival (approximately
50% at 5 years). Studies have shown administration of hepatitis B immune globulin (HBIG) in the
perioperative and early posttransplant periods could delay or prevent recurrent HBV infection in these
transplant recipients. Intravenous or intramuscular administration of HBIG has become the standard of
care for these liver transplant recipients in most liver transplant programs in the United States since
mid-1990. Most therapy protocols administer HBIG in high doses (10,000 IU) during the perioperative
period and first week after transplantation, with the goal of achieving serum hepatitis B surface antibody
(anti-HBs) levels of >500 mIU/mL. Serial levels of anti-HBs are obtained to determine the
pharmacokinetics of HBIG in each patient to guide frequency of HBIG dosing. There is a high degree of
variability in HBIG dosage required to achieve desirable serum anti-HBs levels among transplant
recipients during the first few weeks to months after transplantation. Patients who were hepatitis B
envelope (HBe) antigen positive before transplantation usually require more HBIG to achieve the target
anti-HBs levels, especially in the first week after transplantation. Duration of HBIG therapy varies from 6
months to indefinite among different US liver transplant programs. Protocols providing <12 months of
therapy usually combine HBIG with another effective anti-HBV agent such as lamivudine. See HBV
Infection-Monitoring Before and After Liver Transplantation in Special Instructions.
Useful For: Monitoring serum anti-hepatitis B surface levels during intravenous or intramuscular
hepatitis B immune globulin therapy to prevent hepatitis B virus reinfection in liver transplant recipients
with known previous chronic hepatitis B
Interpretation: Please refer to health care provider's institutional hepatitis B immune globulin (HBIG)
therapy protocol for desirable hepatitis B surface antibody (anti-HBs) levels. Studies indicated that serum
anti-HBs levels needed to prevent hepatitis B virus reinfection were >500 mIU/mL during the first week
after transplantation, >250 mIU/mL during weeks 2 to 12, and >100 mIU/mL after week 12. See HBV
Infection-Monitoring Before and After Liver Transplantation in Special Instructions.
Reference Values:
Not applicable
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 1028
Useful For: Identifying previous exposure to hepatitis B virus Determining adequate immunity from
hepatitis B vaccination
Interpretation: This assay provides both qualitative and quantitative results. A positive result
indicates recovery from acute or chronic hepatitis B virus (HBV) infection, or acquired immunity from
HBV vaccination. This assay does not differentiate between a vaccine-induced immune response and an
immune response induced by infection with HBV. A positive total anti-hepatitis B core (anti-HBc)
result would indicate that the hepatitis B surface antibody (anti-HBs) response is due to past HBV
infection. Positive results (quantitative hepatitis B surface antibody [anti-HBs] levels of > or =12.0
mIU/mL) indicate adequate immunity to hepatitis B from past hepatitis B or HBV vaccination. After
receiving a primary HBV vaccine series, individuals with anti-HBs levels of 12 mIU/mL or greater are
considered protected from hepatitis B in accordance with the CDC guideline.(1) A negative result
(quantitative anti-HBs level of <5.0 mIU/mL) indicates a lack of recovery from acute or chronic
hepatitis B or inadequate immune response to HBV vaccination. The U.S. Advisory Committee on
Immunization Practices does not recommend more than 2 HBV vaccine series in nonresponders.(1)
Indeterminate results (quantitative anti-HBs levels in the range from > or =5 to <12 mIU/mL) indicate
inability to determine if anti-HBs is present at levels consistent with recovery or immunity. Repeat
testing is recommended in 1 to 3 months. See The Laboratory Approach to the Diagnosis and
Monitoring of Hepatitis B Infection in Publications and HBV Infection-Diagnostic Approach and
Management Algorithm in Special Instructions.
Reference Values:
HEPATITIS B SURFACE ANTIBODY
Unvaccinated: negative
Vaccinated: positive
Clinical References: 1. Bonino F, Pratvisuth T, Brunetto MR, Liaw YF: Diagnostic markers of
chronic hepatitis B infection and disease. Antiviral Therapy 2010;15(Suppl 3):35-44 2. Diniz G, Aktas S,
Ortac R, et al: A comparative immunohistochemical study of HBsAg, HBcAg and CD57 in chronic
hepatitis B pediatric patients with and without malignant disorders. Turk J Gastroenterol
2003;14(4):234-238 3. Gerber MA, Thung SN: The diagnostic value of immunohistochemical
demonstration of hepatitis viral antigens in the liver. Human Pathology 1987;18(8):771-774 4.
Sanchez-Quijano A, Jaurequi JI, Leal M, et al: Hepatitis B virus occult infection in subjects with
persistent isolated anti-HBc reactivity. Journal of Hepatology 1993;17(3):288-293 5. Sharma RR, Dhiman
RK, Chawia Y, Vasistha RK: Immunohistochemistry for core and surface antigens in chronic hepatitis.
Trop Gastroenterol 2002;23(1):16-19
Useful For: Diagnosis of acute, recent, or chronic hepatitis B infection in prenatal patients
Interpretation: A reactive screen result confirmed as positive by hepatitis B surface antigen (HBsAg)
confirmatory test is indicative of acute or chronic hepatitis B virus (HBV) infection, or chronic HBV
carrier state. Specimens with reactive screen results but negative (ie, not confirmed) HBsAg confirmatory
test results are likely to contain cross-reactive antibodies from other infectious or immunologic disorders.
Repeat testing is recommended at a later date if clinically indicated. Confirmed presence of HBsAg is
frequently associated with HBV replication and infectivity, especially when accompanied by presence of
hepatitis B envelope (HBe) antigen and/or detectable HBV DNA. See the following in Special
Instructions: -HBV Infection-Diagnostic Approach and Management Algorithm -HBV
Infection-Monitoring Before and After Liver Transplantation -Viral Hepatitis Serologic Profile
Reference Values:
Only orderable as a reflex. For more information see HBAGP / Hepatitis B Surface Antigen Prenatal,
Serum
Negative
Clinical References: 1. Bonino F, Piratvisuth T, Brunetto MR, et al: Diagnostic markers of chronic
hepatitis B infection and disease. Antiviral Therapy 2010;15(3):35-44 2. Servoss JC, Friedman LS:
Serologic and molecular diagnosis of hepatitis B virus. Clin Liver Dis 2004;8:267-281 3. Badur S, Akgun
A: Diagnosis of hepatitis B infections and monitoring of treatment. J Clin Virol 2001;21:229-237
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 1030
transplacentally. Infection of the infant can occur if the mother is a chronic hepatitis B surface antigen
carrier or has an acute HBV infection at the time of delivery. Transmission is rare if an acute infection
occurs in either the first or second trimester of pregnancy.
Useful For: Stand-alone prenatal screening test for chronic hepatitis B in pregnant women
Interpretation: A reactive screen result confirmed as positive by hepatitis B surface antigen
(HBsAg) confirmatory test is indicative of acute or chronic hepatitis B virus (HBV) infection, or
chronic HBV carrier state. Specimens with initially reactive test results, but negative (not confirmed) by
HBsAg confirmation test, are likely to contain cross-reactive antibodies from other infectious or
immunologic disorders. These unconfirmed HBsAg-reactive screening test results should be interpreted
in conjunction with test results of other HBV serologic markers (eg, hepatitis B surface antibody;
hepatitis B core antibody, total and IgM). The presence of HBsAg is frequently associated with HBV
replication and infectivity, especially when accompanied by the presence of hepatitis B envelope (HBe)
antigen and/or detectable HBV DNA.
Reference Values:
Negative
See Viral Hepatitis Serologic Profiles in Special Instructions.
Useful For: Diagnosis of acute, recent, or chronic hepatitis B infection Determination of chronic
hepatitis B infection status
Interpretation: A reactive screen result (signal-to-cutoff ratio [S/CO] > or =1.00, but < or =50.0)
confirmed as positive by hepatitis B surface antigen (HBsAg) confirmatory test (see Method
Description) or a positive screen result (S/CO >50.0) is indicative of acute or chronic hepatitis B virus
(HBV) infection, or chronic HBV carrier state. Specimens with reactive screen results but negative (ie,
not confirmed) HBsAg confirmatory test results are likely to contain cross-reactive antibodies from
other infectious or immunologic disorders. Repeat testing is recommended at a later date if clinically
indicated. Confirmed presence of HBsAg is frequently associated with HBV replication and infectivity,
especially when accompanied by presence of hepatitis B envelope (HBe) antigen and/or detectable
HBV DNA. See the following in Special Instructions: -HBV Infection-Diagnostic Approach and
Management Algorithm -HBV Infection-Monitoring Before and After Liver Transplantation -Viral
Hepatitis Serologic Profile
Reference Values:
Negative
See Viral Hepatitis Serologic Profiles in Special Instructions.
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Clinical References: 1. Bonino F, Piratvisuth T, Brunetto MR, et al: Diagnostic markers of chronic
hepatitis B infection and disease. Antiviral Therapy 2010;15(3):35-44 2. Servoss JC, Friedman LS:
Serologic and molecular diagnosis of hepatitis B virus. Clin Liver Dis 2004;8:267-281 3. Badur S, Akgun
A: Diagnosis of hepatitis B infections and monitoring of treatment. J Clin Virol 2001;21:229-237
Useful For: Confirmation of chronic hepatitis B virus (HBV) infection Quantification of HBV DNA in
serum of patients with chronic HBV infection (previously hepatitis B surface antigen-positive)
Monitoring disease progression in chronic HBV infection and/or response to anti-HBV therapy
Interpretation: The quantification range of this assay is 20 to 170,000,000 IU/mL (1.30-8.23 log
IU/mL). An "Undetected" result indicates that hepatitis B virus (HBV) DNA was not detected in the
specimen. A "Detected" result with the comment, "HBV DNA level is <20 IU/mL (<1.30 log IU/mL).
This assay cannot accurately quantify HBV DNA below this level" indicates that the HBV DNA level is
below the lower limit of quantification for this assay. When clinically indicated, follow-up testing with
this assay is recommended in 1 to 2 months. A quantitative result expressed in IU/mL and log IU/mL
indicates the degree of active HBV viral replication in the patient. Monitoring HBV DNA levels over time
is important for assessing disease progression or monitoring a patient's response to anti-HBV therapy. A
"Detected" result with the comment, "HBV DNA level is >170,000,000 IU/mL (>8.23 log IU/mL). This
assay cannot accurately quantify HBV DNA above this level" indicates that the HBV DNA level is above
the upper limit of quantification for this assay. An indeterminate result with the comment "Inconclusive
Result: Submit a new specimen for testing if clinically indicated" indicates that inhibitory substances may
be present in the specimen. When clinically indicated, collection and testing of a new specimen is
recommended.
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Reference Values:
Undetected
Clinical References: 1. Pawlotsky JM: Hepatitis B virus (HBV) DNA assays (methods and
practical use) and viral kinetics. J Hepatol 2003;39:S31-S35 2. Servoss JC, Friedman LS: Serologic and
molecular diagnosis of hepatitis B virus. Clin Liver Dis 2004;8:267-281 3. Goedel S, Rullkoetter M,
Weisshaar S, et al: Hepatitis B virus (HBV) genotype determination by the COBAS AmpliPrep/COBAS
TaqMan HBV test, v2.0 in serum and plasma matrices. J Clin Virol 2009;45:232-236 4. Chevaliez S,
Bouvier-Alias M, Laperche S, et al: Performance of version 2.0 of the Cobas AmpliPrep/Cobas TaqMan
Real-Time PCR Assay for hepatitis B virus DNA quantification. J Clin Microbiol 2010;48:3641-3647 5.
Lok ASF, McMahon BJ: Chronic hepatitis B: Update 2009. Hepatology 2009;50:661-662
HBV genotype and resistance interpretation is provided by SeqHepB software from Evivar Medical.
The following mutations are reported: reverse transcriptase L80I/V, Il69T, V173L, L180M, A181S/T/V,
T184A/C/F/I/G/S/M/L, S202C/G/I, M204I/V, N236T, M250I/L/V; surface antigen P120T, D144A,
G145R.
Both the HBV RT polymerase and the HBsAg encoding regions are sequenced. Resistance and surface
antigen mutations are reported. In addition, the major HBV genotypes are identified. Mutations in viral
sub-populations below 20% of total may not be detected.
This test is performed pursuant to a license agreement with Roche Molecular Systems, Inc.
Useful For: Testing cadaveric and hemolyzed blood specimens for hepatitis B surface antigen;
FDA-licensed for use with hemolyzed specimens Diagnosis of acute, recent (<6 month duration), or
chronic hepatitis B infection; determination of chronic hepatitis B carrier status
Interpretation: A positive result (reactive screening and confirmed positive by neutralization test;
see Method Description) is indicative of acute or chronic hepatitis B virus (HBV) infection, or chronic
HBV carrier state. A positive (confirmed) neutralization test result is considered the definitive test result
for hepatitis B surface antigen (HBsAg). Specimens that are reactive by the screening test but negative
(not confirmed) by the neutralization test are likely to contain cross-reactive antibodies from other
infectious or immunologic disorders. These unconfirmed HBsAg screening test results should be
interpreted in conjunction with test results of other HBV serological markers (eg, anti-hepatitis B
surface antibody, anti-hepatitis B core total antibody). The presence of HBsAg is frequently associated
with HBV infectivity, especially when accompanied by the presence of hepatitis Be antigen or HBV
DNA.
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Reference Values:
Negative
Clinical References: 1. Servoss JC, Friedman LS: Serologic and molecular diagnosis of hepatitis B
virus. Clin Liver Dis 2004;8:267-281 2. Badur S, Akgun A: Diagnosis of hepatitis B infections and
monitoring of treatment. J Clin Virol 2001 Jun;21(3):229-237
Useful For: Screening and detection of chronic hepatitis C virus infection in nonsymptomatic
individuals Note: In accordance with National Coverage Determination guidance, this test is indicated for
asymptomatic patients born from 1945 through 1965, those with history of injection drug use, or history
of receiving blood transfusion prior to 1992.
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necessarily indicate past or resolved HCV infection. Individuals with such results should be retested for
HCV RNA in 1 to 2 months, to distinguish between patients with past or resolved HCV infection and
those with chronic HCV infection having episodic HCV replication. Presence of HCV antibodies (assay
signal-to-cutoff ratio of <3.8 by EIA or <8.0 by chemiluminescence immunoassay) in individuals with
negative HCV RNA results may be confirmed by HCV Antibody Confirmation, Serum.
Reference Values:
Negative
See Viral Hepatitis Serologic Profiles in Special Instructions.
Clinical References: 1. Carithers RL, Marquardt A, Gretch DR: Diagnostic testing for hepatitis C.
Semin Liver Dis 2000;20(2):159-171 2. Pawlotsky JM: Use and interpretation of virological tests for
hepatitis C. Hepatology 2002;36:S65-S73 3. Centers for Disease Control and Prevention: Testing for
HCV infection: an update of guidance for clinicians and laboratorians. Morb Mortal Wkly Rep
2013;62(18)362-365 4. American Association for the Study of Liver Diseases / Infectious Diseases
Society of America / International Antiviral SocietyUSA. Recommendations for Testing, Managing,
and Treating Hepatitis C. www.hcvguidelines.org Accessed on January 27, 2015
Useful For: Detection and diagnosis of chronic hepatitis C virus infection in symptomatic patients
Interpretation: Chemiluminescence Immunoassay: Reactive hepatitis C virus (HCV) antibody
screening results with signal-to-cutoff (S/CO) ratios of <8.0 are not predictive of the true HCV antibody
status and additional testing is recommended to confirm anti-HCV status. Reactive results with S/CO
ratios of > or =8.0 are highly predictive (> or =95% probability) of the true anti-HCV status, but
additional testing is needed to differentiate between past (resolved) and chronic hepatitis C. A negative
screening test result does not exclude the possibility of exposure to or infection with HCV. Negative
screening test results in individuals with prior exposure to HCV may be due to low antibody levels that
are below the limit of detection of this assay or lack of reactivity to the HCV antigens used in this assay.
Patients with acute or recent HCV infections (<3 months from time of exposure) may have
false-negative HCV antibody results due to the time needed for seroconversion (average of 8 to 9
weeks). Testing for HCV RNA (HCVQU / Hepatitis C Virus [HCV] RNA Detection and Quantification
by Real-Time Reverse Transcription-PCR [RT-PCR], Serum) is recommended for detection of HCV
infection in such patients. RT-PCR: The quantification range of this test is 15 to 100,000,000 IU/mL.
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Negative results indicate that HCV RNA is not detected in the serum. A numerical result indicates the
presence of HCV infection with active viral replication. Positive results with the comment of "HCV
RNA detected, but <15 IU/mL" indicate that the HCV RNA present is at a level below the quantifiable
lower limit of this assay. Follow-up testing by this assay is recommended in 1 to 3 months. Positive
results with the comment of "but >100,000,000 IU/mL" indicate that the level of HCV RNA present is
above the quantifiable upper limit of this assay. A single negative HCV RNA result with positive HCV
antibody status (assay signal-to-cutoff ratio of > or =3.8 by EIA, or > or =8.0 by chemiluminescence
immunoassay), does not necessarily indicate past or resolved HCV infection. Individuals with such
results should be retested for HCV RNA in 1 to 2 months, to distinguish between patients with past or
resolved HCV infection and those with chronic HCV infection having episodic HCV replication.
Presence of anti-HCV antibodies (assay signal-to-cutoff ratio of <3.8 by EIA or <8.0 by
chemiluminescence immunoassay) in individuals with negative HCV RNA results may be confirmed
HCV Antibody Confirmation, Serum.
Reference Values:
Negative
See Viral Hepatitis Serologic Profiles in Special Instructions.
Clinical References: 1. Carithers RL, Marquardt A, Gretch DR: Diagnostic testing for hepatitis C.
Semin Liver Dis 2000;20(2):159-171 2. Pawlotsky JM: Use and interpretation of virological tests for
hepatitis C. Hepatology 2002;36:S65-S73 3. Centers for Disease Control and Prevention: Testing for
HCV infection: an update of guidance for clinicians and laboratorians. Morb Mortal Wkly Rep
2013;62(18):362-365 4. American Association for the Study of Liver Diseases / Infectious Diseases
Society of America / International Antiviral SocietyUSA. Recommendations for Testing, Managing,
and Treating Hepatitis C. www.hcvguidelines.org. Accessed on January 27, 2015
Reference Values:
HCV NS3 Subtype: Not Predicted
Reference Values:
HCV NS5a Subtype: Not Predicted
Reference Values:
HCV NS5a Subtype: Not Predicted
Useful For: Detection of acute hepatitis C virus (HCV) infection before the appearance of HCV
antibodies in serum (ie, <2 months from exposure) Detection and confirmation of chronic HCV
infection Quantification of HCV RNA in serum of patients with chronic HCV infection (HCV
antibody-positive) Monitoring disease progression in chronic HCV infection and/or response to
anti-HCV therapy
Interpretation: This assay has a result range of 15 to 100,000,000 IU/mL (1.18 log to 8.00 log
IU/mL) for quantification of hepatitis C virus (HCV) RNA in serum. An "Undetected" result indicates
that the HCV is absent in the patients serum specimen. A result of "<15 IU/mL (<1.18 log IU/mL)"
indicates that HCV RNA is detected, but the HCV RNA level present cannot be quantified accurately
below this lower limit of quantification of this assay. When clinically indicated, follow-up testing with
this assay is recommended in 1 to 2 months. To assess response-guided therapy eligibility, an
"Undetected" result is required, and a result of "<15 IU/mL mL (<1.18 log IU/mL)" should not be
considered equivalent to an "Undetected" result. A quantitative result expressed in IU/mL and log
IU/mL indicates the degree of active HCV viral replication in the patient. Monitoring HCV RNA levels
over time is important to assess disease progression and/or monitoring a patient's response to anti-HCV
therapy. A result of ">100,000,000 IU/mL (>8.00 log IU/mL)" indicates the presence of active HCV
viral replication, and the HCV RNA level present cannot be quantified accurately above this upper limit
of quantification of this assay. An "Inconclusive" result with the comment "Inconclusive" result. Submit
a new specimen for testing if clinically indicated indicates that inhibitory substance(s) is/are present in
the serum specimen tested. When clinically indicated, collection of a new serum specimen for retesting
is recommended.
Reference Values:
Undetected
Clinical References: 1. Ghany MG, Strader DB, Thomas DL, Seeff LB: Diagnosis, management,
and treatment of hepatitis Can update. Hepatology 2009;49:1335-1374 2. de Leuw P, Sarrazin C,
Zeuzem S: How to use virological tools for the optimal management of chronic hepatitis C. Liver Int
Current as of April 19, 2017 5:12 am CDT 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 1037
2011;31 Suppl 1:3-12 3. Centers for Disease Control and Prevention: Testing for HCV infectionan
update of guidance for clinicians and laboratorians. Mort Morbid Wkly Rpt 2013;62(18):362-365
Useful For: Confirming the presence of hepatitis C virus (HCV)-specific IgG antibodies in serum
specimens that are reactive by HCV antibody screening tests Distinguish between true- and false-reactive
HCV antibody screening test results
Interpretation: A positive result indicates the presence of hepatitis C virus (HCV)-specific IgG
antibodies due to past (resolved) or chronic hepatitis C. Past (resolved) HCV infection (accounting for
about 25% of all HCV-infected patients) can be distinguished from chronic HCV infection (about 75% of
all cases) only by direct detection of HCV RNA using molecular test methods (eg, HCVQU / Hepatitis C
Virus [HCV] RNA Detection and Quantification by Real-Time Reverse Transcription-PCR [RT-PCR],
Serum). HCV RNA is present in acute or chronic hepatitis C but not in past (resolved) HCV infection. A
negative result indicates absence of HCV-specific IgG antibodies. A reactive HCV antibody screening test
result with a negative HCV antibody confirmatory result indicates a probable false-reactive screening test
result. An indeterminate result indicates that HCV-specific IgG antibodies may or may not be present.
Indeterminate results should be interpreted along with patient's risk factors for HCV infection and clinical
findings. Individuals at risk for HCV infection with indeterminate results should be retested with an HCV
antibody confirmatory test in 1 to 2 months to determine the definitive HCV antibody status. Molecular
tests to detect HCV RNA may be necessary to determine HCV infection status in those at-risk
immunocompromised patients with indeterminate HCV antibody confirmatory test results due to delayed
appearance of fully complement of HCV-specific antibodies.
Reference Values:
Negative
Clinical References: 1. Carithers RL, Marquardt A, Gretch DR: Diagnostic testing for hepatitis C.
Semin Liver Dis 2000;20(2):159-171 2. Pawlotsky JM: Use and interpretation of hepatitis C virus
diagnostic assays. Clin Liver Dis 2003;7:127-137 3. Centers for Disease Control and Prevention:
Guidelines for laboratory testing and result reporting of antibody to hepatitis C virus. Morb Mortal Wkly
Rep 2003;52(No. RR-3):1-14 Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5203a1.htm
4. Centers for Disease Control and Prevention: Testing for HCV infection: an update of guidance for
clinicians and laboratorians. Morb Mortal Wkly Rep 2013;62:362-365 Available at:
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6218a5.htm?s_cid=mm6218a5_w
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HCCDD Hepatitis C Virus Antibody in Cadaveric or Hemolyzed
58127 Specimens, Serum
Clinical Information: Hepatitis C virus (HCV) is recognized as the cause of most cases of
post-transfusion hepatitis and is a significant cause of morbidity and mortality worldwide. In the United
States, HCV infection is quite common, with an estimated 3.5 to 4 million chronic HCV carriers. HCV
antibodies are usually not detectable during the early months following infection, but they are almost
always detectable by the late convalescent stage (>6 months after onset of acute infection). These
antibodies do not neutralize the virus, and they do not provide immunity against this viral infection.
Loss of HCV antibodies may occur many years following resolution of infection. Despite the value of
serologic tests to screen for HCV infection, several limitations of serologic testing are known: -There
may be a long delay (up to 6 months) between exposure to the virus and the development of detectable
antibodies. -False-reactive screening test results can occur. -A reactive screening test result does not
distinguish between past (resolved) and present HCV infection. -Serologic tests cannot provide
information on clinical response to antiviral therapy. Positive screening serologic test results should be
followed by a confirmatory or supplemental test, such as line immunoassay (HCVL) for HCV
antibodies or a nucleic acid test for HCV RNA. Although nucleic acid tests provide a very sensitive and
specific approach to directly detect HCV RNA in a patient's blood, they are not suitable for use in
testing cadaveric or hemolyzed serum specimens due to interference of heme with the nucleic acid
amplification processes.
Useful For: Screening cadaveric or hemolyzed serum specimens for hepatitis C virus-specific IgG
antibodies Note: This test is not intended for screening blood, cell, or tissue donors.
Interpretation: All specimens with signal-to-cutoff ratios of > or =1.0 will be considered reactive
and reflexed to the hepatitis C virus (HCV) IgG antibody confirmatory test by line immunoassay
(HCVL) at an additional charge. Additional testing is needed to differentiate between past (resolved)
and chronic hepatitis C. A negative screening test result does not exclude the possibility of exposure to
or infection with HCV. Negative screening test results in individuals with prior exposure to HCV may
be due to antibody levels below the limit of detection of this assay or lack of reactivity to the HCV
antigens used in this assay. Patients with recent HCV infections (<3 months from time of exposure) may
have false-negative HCV antibody results due to the time needed for seroconversion (average of 8 to 9
weeks).
Reference Values:
Negative
Clinical References: 1. Carithers RL, Marquardt A, Gretch DR: Diagnostic testing for hepatitis C.
Semin Liver Dis 2000;20(2):159-171 2. Pawlotsky JM: Use and interpretation of virological tests for
hepatitis C. Hepatology 2002;36:S65-S73 3. Centers for Disease Control and Prevention (CDC):
Testing for HCV infection: an update of guidance for clinicians and laboratorians. MMWR Morb
Mortal Wkly Rep 2013;62(18)362-365
Useful For: Screening cadaveric or hemolyzed serum specimens for hepatitis C virus infection in
nonsymptomatic individuals Note: In accordance with National Coverage Determination guidance, this
test is indicated for asymptomatic patients born from 1945 through 1965, those with history of injection
drug use, or history of receiving blood transfusion prior to 1992.
Interpretation: All specimens with signal-to-cutoff ratios of > or =1.0 will be considered reactive and
reflex to the hepatitis C virus antibody confirmatory test by line immunoassay (HCVL) at an additional
charge. Additional testing is needed to differentiate between past (resolved) and chronic hepatitis C. A
negative screening test result does not exclude the possibility of exposure to or infection with HCV.
Negative screening test results in individuals with prior exposure to HCV may be due to antibody levels
below the limit of detection of this assay or lack of reactivity to the HCV antigens used in this assay.
Patients with recent HCV infections (<3 months from time of exposure) may have false-negative HCV
antibody results due to the time needed for seroconversion (average of 8 to 9 weeks).
Reference Values:
Negative
Clinical References: 1. Carithers RL, Marquardt A, Gretch DR: Diagnostic testing for hepatitis C.
Semin Liver Dis 2000;20(2):159-171 2. Alter MJ, Kuhnert WL, Finelli L: Centers for Disease Control
and Prevention: Guidelines for laboratory testing and result reporting of antibody to hepatitis C virus.
MMWR Morb Mortal Wkly Rep 2003;52(No. RR-3):1-14 3. Pawlotsky JM: Use and interpretation of
virological tests for hepatitis C. Hepatology 2002;36:S65-S73