MAPLE SYRUP URINE DISEASE (MSUD)

Quick Background of the Disease:

Maple Syrup Urine Disease (MSUD) is a rare, genetic metabolism disorder that is often
characterized with a deficiency of an enzyme complex, branched-chain-alpha-keto-acid-
dehydrogenase) which is required then to be metabolized into leucine, isoleucine, and valine.
(National Organization of Rare Disorders, 2017)

CASE STUDY REPORT:

A 46-day-old baby was presented to the Neonatal Intensive Care Unit of a Military
Hospital in Rawalpindi in December 2016. The baby was presented with complaints of lethargy
and not being fed since the fifth day of life. The baby was born through a lower segment
caesarian section at a public sector hospital with uneventful antenatal and intra-partum history.
Then the baby developed lethargy and decreased oral intake on its fifth day of life and was
adamantly admitted to the hospital for 2 days, where he was observed to be experience neonatal
sepsis. The baby as discharged on request but was brought back again to the hospital with signs
of reduced oral intake and lethargy. More so, the baby was presented with hypotonicity and
unresponsive rate of 3/15 on a Glasgow Coma Score (GCS). His weight was just about 3.0 kg
with 48 cm length; Occipito-frontal circumference (OFC) of 35 cm, all that lies within the 50 th
centile for his age and gender. The baby had also diminished reflexes in all four of its limbs.
Pupils remain equally bilateral and reactive to light. The rest of his systemic examination were
unremarkable.

HISTORY (Patient, Family Background):

The patient’s parents were bonded in a consanguinity marriage and has one normal and
healthy male elder sibling. Pelvic inflammatory disease, Gestational diabetes mellitus, Urinary
Tract Infection, and Drug Intake during the course of the mother’s pregnancy was absent. In fact,
the mother had undergone regular antenatal check-up monthly during its course of pregnancy
and all of the scans’ results were completely normal. Their family history is undeniably
unremarkable.

The patient was delivered via lower segment caesarian section in a public sector hospital
that lacks antenatal and intra-partum history that could probably affected the child’s condition.
Only days after his birth, the baby developed lethargy and decreased oral intake on its fifth day
and was rushed to the hospital for 2 days where he was diagnosed with neonatal sepsis, carried
out with broad spectrum of antibiotics for treatment. Upon discharge request, the baby developed
once again recurring reduced oral intake and lethargy constantly. Another diagnosis was brought
up, bringing the baby with hypotonicity behavior and unresponsiveness rate of 3/15 via Glasgow
Coma Score (GCS).

SIGNS AND SYMPTOMS:

 Lethargy
 Reduced oral intake
 Hypotonic
  Unresponsiveness with a rate of 3/15 (under Glasgow Coma Score)

PHYSICAL EXAMINATION:
Age: 46 day old/Male
Weight: 3.0 kg
Length: 48 cm
Occipito-frontal circumference (OFC): 35 cm
Muscle tone: Floppy/Hypotonic

 Reflexes in all four limbs are diminished

 Pupils shows bilaterally equal and reactive to light
 Presented to the Neonatal Intensive Care Unit with complaints of lethargy and reduced
oral intake

GENETIC ASSESSMENT:
Maple Syrup Urine Disease (MSUD) is a rare, autosomal recessive disorder that is
characterized by branched-chain α-keto-acid dehydrogenase (BCKAD) complex malfunction.
This condition is inherited and may be passed from generation to generation. It is caused by a
defect in 1 out of 3 genes present in the body where it won’t be able to break down amino acids
such as leucine, isoleucine, and valine that can lead to the accumulation of these chemicals in the
blood.

LABORATORY FINDINGS:
Initial laboratory findings revealed a normal complete blood count (CBC), prothrombin
time (PT)/activated partial thromboplastin time (APTT), C-reactive protein (CRP), and blood
glucose levels. His arterial blood gas revealed to be experiencing metabolic acidosis. CSF
examination values were normal for cell count, proteins, and glucose. A workup routine for
inborn error in metabolism was done and initiated, revealing the baby’s plasma lactate to be
slightly increased and plasma ammonia level was found to be 240 μmol/L. Elevated plasma
leucine and isoleucine levels were presented on the plasma amino acid analysis by ion exchange
chromatography performed. CSF was also analyzed through the use of high performance liquid
chromatography which revealed abnormal levels of leucine and isoleucine count, however,
valine was reported to be less than 1.

PLASMA AMINO ACID ANALYSIS BY ION EXCHANGE CHROMATOGRAPHY

 CSF AMINO ACID ANALYSIS BY HPLC

On a CT scan performed, upon requisition, his brain revealed hypo-attenuation of white

matter in bilateral cerebral hemispheres with effacement of extra cerebral CSF spaces and slit-
like lateral ventricles suggests cerebral edema (brain swelling), reason why his Glasgow Coma
Scale results only for 3/15, interpreted as severe brain injury.

GLASGOW COMA SCALE/SCORE (GCS)

JUSTIFY THE DIAGNOSIS:

After several observation done to the patient, the physician figured out the condition to be
diagnosed to the 46-day-old baby. Upon examination and workup routine done to the patient,
results of elevated leucine and isoleucine levels was then concluded to be one of the factors why
the baby was experiencing lethargy (feeling of being sluggish and often sleepy) and reduced oral
intake. Due to the remarkably increased values in its CSF specimen, a CT scan was order by the
physician. The physical examination result of the patient based on its 35 cm occipito-frontal
circumference of the child didn’t established any relation since it is within normal range for its
age and gender but the results of the CSF and Plasma amino acid analysis led into the discovery
of hypo-attenuation of white matter in bilateral cerebral hemispheres with effacement of extra
cerebral CSF. Reason behind why the Glasgow Coma Scale, a common scoring system used to
describe level of consciousness of a person, of the patient is below 8 which can be interpreted for
the patient to be having severe brain traumatic injury.
 The findings done had led the physician to a conclusion of the patient having a condition
called Maple Syrup Urine Disease, given that the baby was showing the signs and symptoms of
neurological dysfunction, including lethargy and poor feedings. With the classical signs and
symptoms presented by the patient even after birth was accused to be involved as an inborn
genetic metabolism disorder yet the consanguinity marriage between the parents of the patient
was not yet proven to be the reason behind on how the patient acquired the said disease. But
according to studies, parents having consanguinity marriage could have a higher chance of
carrying same abnormal gene that could possibly increase too, the risk of developing a child with
recessive disorder such as Maple Syrup Urine Disease. Even though the mother didn’t have
experience of abnormalities during her course of pregnancy, since the disease is considered to be
rare, it may have developed from within and didn’t had an effect to the mother

To be able to prevent worsening the condition, the physician opted to deliver a treatment
to the patient through injecting an oral Thiamine which will help improved the condition of the
baby. Thiamine-response treatment is said to be effective in treating Maple Syrup Urine Disease
since it will provide an intervention on the patients’ diet, maintaining their metabolic condition
normal for a long period of time. Constantly balancing the diet of the patient would most likely
improve their condition since constant sustained balance would provide normal biochemistry and
development. More than a week had passed, the baby’s condition was already improving, and
another Glasgow Coma Scale was performed revealed a result of 12/15 rate which is considered
to be moderate or normal. Counselling was performed to the family regarding the complications
that may arise and the risks of reoccurrence if another pregnancy was made by the family.
REFERENCES:

(PDF) CLASSIC MAPLE SYRUP URINE DISEASE IN A 46-DAY-OLD BABY: A CASE

REPORT. ResearchGate.
https://www.researchgate.net/publication/325072163_CLASSIC_MAPLE_SYRUP_URIN
E_DISEASE_IN_A_46-DAY-OLD_BABY_A_CASE_REPORT.

Centers for Disease Control and Prevention. (2001, August 23). Growth Charts - Data Table of
Infant Head Circumference-for-age Charts. Centers for Disease Control and Prevention.
https://www.cdc.gov/growthcharts/html_charts/hcageinf.htm.

Maple Syrup Urine Disease. NORD (National Organization for Rare Disorders). (2020, June 5).
https://rarediseases.org/rare-diseases/maple-syrup-urine-disease/.

MediLexicon International. Cerebral edema: Symptoms, causes, treatment, outlook. Medical

News Today. https://www.medicalnewstoday.com/articles/322475.

U.S. National Library of Medicine. Maple syrup urine disease: MedlinePlus Medical
Encyclopedia. MedlinePlus. https://medlineplus.gov/ency/article/000373.htm.

What Is the Glasgow Coma Scale? BrainLine. (2018, July 25).

https://www.brainline.org/article/what-glasgow-coma-scale.