Pediatrics
Congenital Immunodeficiency Disorders
T-cell Disorders
DiGeorge syndrome
- Chromosomal deletion in 22q11 resulting in :
1- Thymic hypoplasia:
a) Recurrent viral/fungal infections (cos of insufficient T cells)
b) CXR: absence of thymic shadow
2- Parathyroid hypoplasia :
a) Decreased Serum Calcium.
b) Tetany
3- Congenital heart disease
4- Abnormal facial structure
Treatment:
1- Calcium, vitamin D,
2- Thymic transplant,
3- Bone marrow transplant,
4- Surgical correction of heart abnormalities;
5- IVIG or prophylactic antibiotics may be helpful
Chronic mucocutaneous candidiasis
- Persistent infection of skin, mucous membranes, and nails by
Candida albicans from T-cell deficiency.
- Frequent associated adrenal Pathology
Diagnosis:
- Poor reaction to cutaneous C. albicans anergy test
- Possible decreased IgG
Treatment:
Antifungal agents (e.g., fluconazole)
Disease
Chronic Granulomatous
Disease (CGD)
Hyper-IgE disease
(Job syndrome)
Chediak-Higashi
Syndrome
Leukocyte Adhesion
Deficiency
( types 1 and 2 )
Inability of neutrophils to leave
circulation
Complement
deficiencies
B-cell Disorder Combined B-cell & T-cell Disorders
X-linked (Bruton's) agammaglobulinemia Severe combined immunodeficiency syndrome (SCID)
- X-linked disorder asscoaited with defect in BTK, a tyrosine kinase - Absent T cells and abnormal antibody function resulting in :
gene  No B-cells maturation , with boys experiencing recurrent severe immune compromise :
bacterial infections after 6 months of age 1- Decreased WBCs (significant)
- Abnormal B-cell differentiation resulting in: 2- Decreased immune globulins
1- Low B-cell  No B cells in peripheral smear - Patients experience significant recurrent infections by all types of
2- Antibody levels  low total immunoglobulin levels pathogens from an early age. (frequently fatal at an early age)
Treatment: Treatment:
1- IVIG 2- Appropriate antibiotics 3- Supportive pulmonary care 1- IVIG 2- Appropriate antibiotics 3- bone marrow transplant
IgA deficiency  no live or attenuated vaccines should be administered
- Abnormal immune globulin production by B cells :
 Specific IgA deficiency Wiskott-Aldrich syndrome
- Decreased IgA with normal levels of other immune globulins - X-linked recessive disorder caused by a defective gene encoding
- Patients have increased incidence of : for Wiskott-Aldrish Syndrome Protein (WASP)
1- Respiratory 2- Gastrointestinal infections - Presentation is classically Young boy with (Triad) :
Treatment: 1- Infection Susceptibility to encapsulated bacteria &opportunistics
1- IVIG with caution (small risk of anaphylaxis) 2- Eczema
2- Prophylactic antibiotic 3- Thrombocytopenia  initial presentation often present at birth
Hyper IgM disease with petechie/bruises/bleeding from circumcision/bloody stools
- Defect in T-cell CD40 ligand resulting in  poor interaction with B Lab:
cells : 1- High IgM 1- Decreased IgM with
2- Low IgG and IgA 2- High IgG & IgA
- Patients have increased incidence of encapsulated bacteria : 3- Moderate decrease in T-cells
1- Respiratory 2- Gastrointestinal infections 4- Decreased platelets
Possible in Hgb, Hct, platelets, neutrophils 5- Poor antibody responses to polysaccharide antigens
Treatment: Treatment:
5- IVIG with caution (small risk of anaphylaxis) 1- IVIG
6- Prophylactic antibiotic 2- Prophylactic antibiotic
7- bone marrow transplant 3- Bone marrow transplant
Common variable immunodeficiency 4- Splenectomy
- Autosomal disorder of B-cell differentiation resulting in :
1- Low immune globulin levels Ataxia-telangiectasia
2- Decreased CD4:CD8 T-cell ratio - Autosomal recessive disorder causing :
3- Poor response to vaccines; 1- Cerebellar dysfunction
- Patients have : develop after 3 years of age
2- Cutaneous telangiectasias
A) increased incidence of encapsulated bacteria :
Lab:
1- Respiratory 2- Gastrointestinal infections  in 2nd decade of life
3- Dcrease WBC  recurrent pulmonary infections begin a few years later
B) Risk of malignant neoplasms and autoimmune disorders 4- Decreases IgA
family history shows both men and women affected Treatment:
Treatment: 1- IVIG
1- IVIG with caution (small risk of anaphylaxis) 2- Prophylactic antibiotics may be helpful,
2- Prophylactic antibiotic BUT treatment usually unable to limit disease progression
Phagocytic cell disorders
Description Diagnosis Treatment
Defect in phagocytic cells (neutrophils cannot digest - Most common clinical findings:
engulfed bacteria ) due to : dysfunction of NADPH 1- Chronic Lymphadenopathy 1- Prevention of infection with :
oxidase enzyme resulting in : A) Trimethoprim-sulphamethoxazole (Daily)
2- HepatoSplenomegaly
Recurrent & uncontrolled infections with catalase 3- Infections  Cutaneous cellulitis B) Gamma interferon (3 times a week)
positive organisms : Perirectal abscess formation
1- Aspergillus spp. Pulmonary abscess formation 2- Bone marrow transplantation
2- Burkholderia cepacia
4- Hypergammaglobulinemia
3- Klebsiella pneumoniae
5- Other:
4- S.aureus
- Anemia of chronic disease - underweight
5- Serratia marcescens
- Chronic diarrhea - gingivitis
They are not susceptible to catalase negative organisms: Diagnosis:
1- Streptococcus pyogens Is made by 1- Nitroblue Tetrazolium (NBT) slide test
2- Streptococcus pneumoniae 2- Flow cytometry
3- H.influnzae 3- Cytochrome C reduction
A- Defect in : 1- Prophylactic antibiotics
- Neutrophil chemotaxis
1- Increased IgE 2- Skin hydration
- T-cell signaling
B- Overproduction of IgE resulting in : 2- Increased eosinophils 3- Emollient use
3- Defective chemotactic response of neutrophils
1- Chronic pruritic dermatitis
on stimulation
2- Recurrent staphylococcal infections
- Skin infection & abscesses
- Respiratory tract infections
+ commonly:
Coarse facial features & retained 1ry teeth & bone fractures
Multisystem disorder with :
Autosomal recessive , characterized by Decreased (3) : 1- Frequent bacterial infections  usually S.aureus 1- Prevention of infection with :
1- Degranulation 2- Mild coagulopathy A) Trimethoprim-sulphamethoxazole (Daily)
2- Granuopoiesis 3- Pancytopenia
3- Chemotaxis B) Ascorbic acid (daily)
4- Peripheral & cranial neuropathy
Resulting in Recurrent infections with 5- Partial oculocutaneous albinism
6- Hepatosplenomeglay 2- Bone marrow transplantation
1- Recurrent Staphylococcus aureus,
2- Streptococcal 7- Progressive Lymphoproliferative Syndrome
3- Gram-negative bacteria Diagnosis: Findings will confirm diagnosis :
4- Fungal infections 1- Neuropenia
2- Large granules (lysosomes) seen in
granulocytes(neutrophils) on peripheral smear
Failure of innate host defenses against : bacteria/fungi 1- Recurrent bacterial infections of (URT & skin)
1- Prophylactic antibiotics
due to defective in: tethering+adhesion+targeting of 2- History of delayed separation of umbilical cord
3- Severe gingivitis & Periodynitis & alveolar bone 2- In type 1 : Bone marrow transplant needed
myeloid leukocytes to sites of microbial invasion.
loss  early loss of deciduous & permanent teeth. 3- In type 2 : treated with fucose supplementation
Because of :
4- In type 2 disease : Short stature, abnormal facies,
(type 1)  Abnormal leukocyte Integrins
and cognitive impairment seen
(type 2)  Abnormal leukocyte E-selectin Hall mark of disease :
Neutrophilia WITHOUT ploymorphs in infected tissue/pus
Complement disorders
Multiple inherited deficiencies of one or more 1- Hemolytic complement test results are abnormal
complement components, resulting in : and indicate problem in pathway 1- Appropriate antibiotics
1- Recurrent bacterial infections 2- Direct testing of components can detect exact 2- Treat autoimmune disorders, as needed
2- Predisposition to autoimmune disorders (SLE) deficiency
 Metabolic Errors
Inborn Errors of Carbohydrate Metabolism
Carbohydrates are metabolized into three principal monosaccharides: Fructose , Galactose , Glucose
Fructose
Disease Description Diagnosis Treatment
- Autosomal recessive Benign, asymptomatic condition, since fructose is not
Essential fructosuria - Involves a deficiency of fructokinase trapped in cells.
Symptoms: fructose appears in blood and urine.
- Autosomal recessive - Symptoms present following consumption of fruit, juice, Reduce intake of both :
- Hereditary deficiency of aldolase B  Fructose-1-P or honey: hypoglycemia, cirrhosis, jaundice, vomiting 1- Fructose and
Fructose intolerance accumulates, causing:  in available phosphate - Diagnosis : 2- Sucrose (glucose + fructose).
which results in : 1- Urine dipstick will be –ve (tests for glucose only)
1- Inhibition of glycogenolysis 2- Reducing sugar can be detected in the urine
2- Inhibition of gluconeogenesis (nonspecific test for inborn errors of carbohydrate metabolism).
MedicoNotes provide high-yield USMLE Galactose notes , written professionally in tables over the
Symptoms: (mild condition)
usualdeficiency
Galactokinase long text-notes
- Autosomal recessiveto help you
- Involves a deficiency of galactokinase
study 1-easily
May initially and
present aseffectively.
: - failure to track objectsWe
or summarized many
- to develop a social smile
 Galactitol accumulates if galactose is present in diet 2- Bilateral cataracts
diseases in only
 Present with: Cataract only
few papers with tips &3-tricks
Otherwise is asymptomatic in diagnosis, differential diagnosis and
Galactose appears in blood and urine
Newborn with:
management
Classic Galactosemia to help
- Autosomal recessive
you recalling the
- Deficiency of galactose-1-phosphate uridyltransferase
right
1- Failureanswer
to thrive immediately. Eliminate of both from diet :
This patient is at risk of : 2- Bilateral Cataract 1- Galactose
E.Coli neonatal sepsis
Damage is caused by : 3- Jaundice + Hepatosplenomegaly 2- Lactose (galactose + glucose)
Our USMLE notes
Accumulationare
of toxicwritten
Failure to early diagnosis & intervention :
1- Hepatic cirrhosis
from
substances (including confident sources and famous Question banks. We
galactitol, 4- Hypoglycemia: lethargic/irritable/poor feeding/
which accumulates in the lens of the eye).
2- Mental retardation Persistent vomiting
help you not only to pass USMLE, but also to get high scores with our high yield notes.
3- Phosphate depletion 5- Convulsions: jerky movement of his limbs
 Manifestations : as galactosemia
Uridyl diphosphate galactose-
+
4-epimerase deficiency
To download the full file and the Glucose
other USMLE files, please click here
1- Hypotonia 2- Nerve deafness

Sorbitol - Alternative method of trapping glucose in the cell is to - Tissues with an insufficient amount of sorbitol

to SUBSCRIBE and get a lifetime membership.

Glucoseby Aldose reductase Sorbitol
It can be obtained by reduction of glucose,
changing aldehyde group to a hydroxyl group
- Schwann cells, retina, and kidneys have only
aldose reductase.
- Lens has primarily aldose reductase.
convert it to its alcohol counterpart, called sorbitol,
via aldose reductase.
dehdrogenase are at risk for intracellular sorbitol
accumulation, causing osmotic damage:
- Some tissues then convert sorbitol to fructose using 1- Cataracts
by sorbitol dehdrogenase 2- Retinopathy
- High blood levels of galactose also result in conversion to the 3- Peripheral neuropathy (seen with chronic hyperglycemia).
osmotically active galactitol via aldose reductase.

Disaccharide sugar derived from Glucose & Galactose that is found in milk
Insufficient lactase enzyme  dietary lactose
intolerance.
Lactase deficiency - Primary: : age-dependent decline after childhood
(absence of lactase-persistent allele).
Lactase functions on the brush border to - Secondary: loss of brush border due to gastroenteritis
digest lactose (in human and cow milk) into :
1- Glucose
(e.g., rotavirus), autoimmune disease, etc.
2- Galactose - Congenital lactase deficiency: rare, defective gene.
Lactose
Symptoms: Bloating, cramps, flatulence, osmotic diarrhea. 1- Avoid dairy products or add lactase pills to diet
Diagnosis:
2- lactose-free milk.
1- Stool: demonstrates  pH
2- Breath: shows  hydrogen content with
lactose tolerance test.
3- Intestinal biopsy reveals: normal mucosa in
patients with hereditary lactose intolerance.

Inborn Errors of Amino Acids Metabolism

- Autosomal recessive (Incidence ≈ 1:10,000) Symptoms: Screening :
Phenylketonuria - Due to  Phenylalanine hydroxylase or 1- Growth retardation Screened for 2–3 days after birth
… ……  Tetrahydrobiopterin cofactor (malignant PKU) 2- Intellectual disability (normal at birth because of maternal enzyme during fetal life)
Tyrosine becomes essential. 3- Seizures
Phenylketones: 4- Fair skin Treatment:
- phenylalanine leads to excess phenylketones in urine
1- phenylacetate, 5- Eczema  phenylalanine and  tyrosine in diet.
2- phenyllactate 6- Musty body odor (Disorder of aromatic amino
3- phenylpyruvate. Maternal PKU: PKU patients must avoid the artificial sweetener aspartame,
acid metabolism
- lack of proper dietary therapy during pregnancy. which contains phenylalanine.
- Findings in infant:
growth retardation, microcephaly, intellectual disability,
congenital heart defects.
- Autosomal recessive. Symptoms:
- Congenital deficiency of homogentisate oxidase in 1- Dark connective tissue,
Alkaptonuria 2- Brown pigmented sclerae,
the degradative pathway of tyrosine to fumarate.
(ochronosis) 3- Urine turns black on prolonged exposure to air.
4-May have debilitating arthralgias
(homogentisic acid toxic to cartilage).
Symptoms: Treatment :
1- Intellectual disability Type 1:
2- Lens subluxation (downward and inward)  methionine,  cysteine,  B12 and folate in diet
Types (all autosomal recessive): 3- Tall stature
4- Osteoporosis Type 2 :
Homocystinuria 1- Cystathionine synthase deficiency
5- Kyphosis  B6 and  cysteine in diet
2-  affinity of cystathionine synthase for pyridoxal 6- Thrombosis & atherosclerosis (stroke and MI)
phosphate Type 3 :
3- Homocysteine methyltransferase (methionine Diagnosis:  methionine in diet
synthase) deficiency  homocysteine in urine
All forms result in excess homocysteine
- Autosomal recessive Common (1:7000)  Excess cystine in the urine can lead to precipitation of Treatment:
Cystinuria - Hereditary defect of : hexagonal cystine stones. 1- Urinary alkalinization
1- Renal PCT and (e.g., potassium citrate, acetazolamide) and
Cystine is made of 2 cysteines 2- Intestinal amino acid transporter for Diagnosis: 2- Chelating agents  solubility of cystine stones
connected by a disulfide bond. Urinary cyanide-nitroprusside test is diagnostic.
Cysteine, Ornithine, Lysine, and Arginine (COLA). 3- Good hydration.
 Storage Disorders
Glycogen storage diseases

MedicoNotes provide high-yield USMLE notes , written professionally in tables over the
usual long text-notes to help you study easily and effectively. We summarized many
diseases in only few papers with tips & tricks in diagnosis, differential diagnosis and
management to help you recalling the right answer immediately.
Our USMLE notes are written from confident sources and famous Question banks. We
4 Diseases are Autosomal recessive Very Poor Carbohydrate Metabolism
help you not only to pass USMLE, but also to get high
Disease Deficient Enzyme scores with our high yieldTreatment
Description notes.
- Symptoms:
1- Severe fasting hypoglycemia 1- Frequent oral glucose/cornstarch

To download the full file and the other USMLE files, please click here
Von Gierke disease
(type I)
Glucose-6-phosphatase 2- Hepatomegaly
3-  glycogen in liver
2- Avoidance of fructose & galactose.

4-  blood lactate

to SUBSCRIBE and get a lifetime membership.

Pompe disease
(type II) Lysosomal a-1,4-glucosidase
(acid maltase)
- Symptoms:
1- Cardiomyopathy
Pompe trashes the Pump 2- Systemic findings leading to early death
(heart, liver, and muscle).
- Symptoms:
Cori disease Debranching enzyme 1- Milder form of type I with normal blood lactate levels
(type III) (a-1,6-glucosidase) 2- Gluconeogenesis is intact
- Symptoms:
McArdle disease  glycogen in muscle, but cannot break it down, leading to :
(type V) Skeletal muscle glycogen 1- Painful muscle cramps,
Phosphorylase (myophosphorylase) 2- Myoglobinuria(red urine) with strenuous exercise
McArdle = Muscle.
3- Arrhythmia from electrolyte abnormalities.
Lysosomal storage diseases
Each is caused by a deficiency in one of the many lysosomal enzymes. Results in an accumulation of abnormal metabolic products.

Sphingolipidoses
Diseases Inheritance Deficient Enzyme Accumulated substance Findings
1- Cardiovascular/renal disease
Fabry disease X-linked recessive a-galactosidase A Ceramide trihexoside 2- Angiokeratomas
3- Peripheral neuropathy of hands/feet
Gaucher disease (Most Glucocerebrosidase 1- Hepatosplenomegaly
common) Glucocerebroside 2- aseptic necrosis of Femur
(B-glucosidase)
3- Bone Crises
Ttreatment : 4- Pancytopenia
recombinant 5- Gaucher cellsA(lipidladen macrophages resembling
glucocerebrosidase. crumpled tissue paper)

Niemann-Pick disease 1- Hepatosplenomegaly

2- Progressive Neurodegeneration
Autosomal Recessive Sphingomyelinase Sphingomyelin 3- “Cherry-red” spot on macula
4- Foam cells (lipidladen macrophages) B
Tay-Sachs disease 1- NO hepatosplenomegaly (vs. Niemann-Pick)
2- Progressive Neurodegeneration
Hexosaminidase A GM2 ganglioside 3- Cherry-red” spot on macula C
4- Developmental delay
5- Lysosomes with onion skin
1- Optic atrophy
- Galactocerebroside 2- Peripheral neuropathy
Krabbe disease Galactocerebrosidase
- Psychosine 3- Developmental delay
4- globoid cells
Metachromatic 1- Central and peripheral Demyelination with ataxia
Arylsulfatase A Cerebroside sulfate
leukodystrophy 2- Dementia
Mucopolysaccharidoses
1- Hepatosplenomegaly
Hurler syndrome Autosomal Recessive 2- Airway obstruction
a-L-iduronidase - Heparan sulfate 3- Corneal clouding
- Dermatan sulfate 4- Developmental delay
5- Gargoylism
Hunter syndrome Iduronate sulfatase Mild Hurler + aggressive behavior, NO corneal clouding
X-linked recessive
 Vitamins Disorders
Function Deficiency Excess
Fat Soluble Vitamins
1- Antioxidant 3 Eyes : Acute toxicity
2- Constituent of visual pigments (retinal) 1- Night blindness (nyctalopia) 1- Nausea, vomiting, vertigo 2- Blurred vision.
3- Essential for normal differentiation of epithelial cells into 2- Corneal degeneration (keratomalacia) Chronic toxicity—
Vitamin A (retinol) specialized tissue (pancreatic cells, mucus-secreting cells) 3- Bitot spots on conjunctiva 1- Alopecia, 2- Arthralgias 3- Pseudotumor cerebri.
Found in liver and leafy vegetables
4- Prevents squamous metaplasia 4- Dry skin (e.g., scaliness) 5- Hepatic toxicity and enlargement
Immunity: Immunosuppression 6- Teratogenic (cleft palate, cardiac abnormalities),
5- Used to treat: Measles & AML subtype M3. ⊝ pregnancy test and reliable contraception are required
1- Antioxidant SCurvy : to a Collagen synthesis defect
2- Facilitates iron absorption by reducing it to Fe2+ state. 1- Nausea, vomiting, diarrhea, fatigue
1- Swollen gums 
- Ancillary treatment for methemoglobinemia by reducing 2- Calcium oxalate nephrolithiasis
Vitamin C (ascorbic acid) 2- Anemia
Fe3+ to Fe2+. 3- Bruising 4- petechiae, 5-hemarthrosis 3-  risk of iron toxicity in predisposed individuals
Found in fruits and vegetables. (e.g., those with transfusions, hereditary
3- Necessary for hydroxylation of proline and lysine in 6- Perifollicular & subperiosteal hemorrhages
collagen synthesis. hemochromatosis).
7- Poor wound healing, 8- “corkscrew” hair.
MedicoNotes provide high-yield USMLE notes , written professionally in tables over the
4- Necessary for dopamine β-hydroxylase, which converts
dopamine to NE. Immunity: Weakened immune response.
Vitamin D In children : Rickets  Seen in granulomatous disease ( activation of vitamin D
(bone pain and deformity)
1-  Intestinal absorption of calcium and phosphate.
usual long text-notes
D2 = ergocalciferol—ingested from plants.
to help you study easily and
2- bone mineralization.
D3 = cholecalciferol—consumed in milk,
In adults: Osteomalacia
effectively.
+ hypocalcemic tetany. We summarized
(bone pain & muscle weakness)
many
by epithelioid macrophages ).
1- Hypercalcemia / Hypercalciuria
formed in sun-exposed skin (stratum basale).
Vit. D. Deficiency is exacerbated by : 2- Loss of appetite
diseases in only few papers with tips & lowtricks
25-OH D3 = storage form.
1,25-(OH)2 D3 (calcitriol) = active form. inpigmented
sun exposure, diagnosis,
skin, prematurity. differential 3- Stupordiagnosis and
1- Hemolytic anemia 2- Acanthocytosis
1- Antioxidant :
management
Vitamin E
(tocopherol/tocotrienol)
to help
(protects you
RBCs and membranesrecalling the
from free radical damage). right answer
3- Muscle weakness
4- Posterior immediately.
column and spinocerebellar tract demyelination :
2- Can enhance anticoagulant effects of warfarin. - Neurologic presentation may appear similar to vitamin B12
deficiency, but without: megaloblastic anemia, hypersegmented
neutrophils, or  serum methylmalonic acid levels.
Our USMLE notes
Vitamin K
- Cofactor for are written
the γ-carboxylation from
of glutamic
various proteins required for blood clotting.
confident
acid residues on sources
1- Neonatal hemorrhage with PTandand  aPTTfamous Question banks. We
BUT normal bleeding time
(phytomenadione, (neonates have sterile intestines  unable to synthesize vit. K).
helpphytonadione)
phylloquinone, you not - only to pass
Synthesized by intestinal flora.
USMLE,
K is for Koagulation.
but also to getare given
neonates high vitaminscores with
K injection at birth to our high yield notes.
Necessary for the maturation of 1- Clotting factors II, VII, IX, X prevent hemorrhagic disease of the newborn.
Warfarin—vitamin K antagonist. 2- Proteins C and S. -- Also occur after prolonged use of broad-spectrum antibiotics

To download the full file andWater

theSoluble
other USMLE files, please click here
Vitamins
Thiamine PyroPhosphate (TPP), a cofactor for several To determine thiamine deficency is to do TRANSKETOLASE ASSAY
Vitamin B1 (thiamine) dehydrogenase enzyme reactions: Think ATP Wernicke-Korsakoff syndrome: Dry beriberi :

to SUBSCRIBE and get a lifetime membership.

Wernicke-Korsakoff syndrome & Beriberi
Seen in :
1- α-ketoglutarate dehydrogenase (TCA cycle)
2- Transketolase (HMP shunt)
3- Pyruvate dehydrogenase (links glycolysis to TCA cycle)
Damage to 1- Medial dorsal nucleus of thalamus
2- Mammillary bodies.
Classic triad:
1- Polyneuritis: Symmetrical peripheral neuropathy
with sensory & motor impairment
2- Symmetrical muscle wasting.
1- Malnutrition 4- Branched-chain ketoacid dehydrogenase Wernicke: 1- Cerebellar damage : Ataxia
2- Alcoholism (2ry to malnutrition and 2- Ophthalmoplegia Wet beriberi :
malabsorption)  Most common
Deficiency:
Korsakoff: 3- psychiatric symptoms: Confusion + 1- Neuropathy
Impaired glucose breakdown  ATP depletion worsened by
Diagnosis made by : 1- Confabulation : Inventing something to justify wrong as true 2- High-output cardiac failure
glucose infusion; highly aerobic tissues (e.g., brain, heart) are
 in RBC Transketolase activity following (because of destruction of mamillary body) (dilated cardiomyopathy),
affected first.
vitamin B1 administration. 2- Personality change 3- Edema.
3- Memory loss (permanent)
Deficiency  2 C’s of B2.
Vitamin B2 (riboflavin) Component of flavins FAD and FMN, used as cofactors in redox
reactions, e.g., succinate dehydrogenase reaction in TCA cycle. Cheilosis (inflammation of lips, scaling and fissures at the corners of the mouth),
FAD and FMN are derived from riboFlavin glossitis / Pharyngitis /edema & erythema of mouth / megenda tongue
(B2 ≈ 2 ATP). Corneal vascularization. / photophobia/ conjunctivitis ….. Seborrhic dermatitis
Vitamin B3 (niacin) - Constituent of NAD+, NADP+ (used in redox reactions) 1- Glossitis (beefy tongue)
- Derived from tryptophan. 2- Severe deficiency leads to Pellagra : 3 D’s of B3 1- Facial flushing (induced by prostaglandin, not histamine;
NAD derived from Niacin (B3 ≈ 3 ATP).
- Synthesis requires vitamins B2 and B6.  Diarrhea, can avoid by taking aspirin with niacin)
- Used to treat dyslipidemia :  Dementia (also hallucinations), 2- Hyperglycemia
Causes of severe deficiency : 1- lowers VLDL  Dermatitis : 3- hyperuricemia.
1- Hartnup disease (tryptophan 2- raises levels of HDL. a- C3/C4 dermatome circumferential
absorption) “broad collar” rash *Casal necklace]
2- Malignant carcinoid syndrome b- Hyperpigmentation & thickened
(tryptophan metabolism) skin of sun-exposed limbs
3- Isoniazid ( vitamin B6). c- Rash is burning.
4- Malabsorption (Ulverative colitis)
- Essential component of : 1- Alopecia 2- Adrenal insufficiency.
Vitamin B5 (pantothenic acid) 1- coenzyme A (CoA, a cofactor for acyl transfers) 3- Dermatitis 4- Enteritis,
B5 is “pento”thenic acid. 2- Fatty acid synthase.
- Converted to pyridoxal phosphate (PLP), a cofactor used in : 1- Hyperirritability
1- Transamination (e.g., ALT and AST), 2- Convulsions
2- Decarboxylation reactions,
3- Peripheral neuropathy :
Vitamin B6 (pyridoxine) 3- Glycogen phosphorylase.
- Deficiency inducible by isoniazid & OCP
4- Synthesis of :
- Cystathionine, Heme, Niacin, Histamine, 4- Sideroblastic anemias
- Neurotransmitters including serotonin, epinephrine, - due to impaired hemoglobin synthesis & iron excess.
norepinephrine (NE), dopamine, and GABA.
- Cofactor for carboxylation enzymes (which add alpha 1-carbon - Relatively rare.
group): - Caused by: 1- Antibiotic use
* Pyruvate carboxylase: pyruvate (3C)  oxaloacetate (4C) 2- Excessive ingestion of raw egg whites.
Vitamin B7 (biotin)
* Acetyl-CoA carboxylase: acetyl-CoA (2C)  malonyl-CoA (3C) ..1- Alopecia 2- Dermatitis 3- Enteritis
* Propionyl-CoA carboxylase: propionyl-CoA (3C)  4- Fasting hypoglycemia 5- Bowel inflammation
methylmalonyl-CoA (4C) 6- Muscle pain
Vitamin B9 (folate) 1- Macrocytic, megaloblastic anemia
Most common vitamin deficiency in U.S - Converted to tetrahydrofolic acid (THF), a coenzyme for :
2- Hypersegmented polymorphonuclear cells (PMNs)
1-carbon transfer/methylation reactions.
Deficiency can be caused by several drugs : 3- Glossitis
1- Phenytoin - Important for synthesis of nitrogenous bases in DNA & RNA
 NO neurologic symptoms (as opposed to vitamin B12 deficiency).
2- Sulfonamides - Found in leafy green vegetables.
3- Methotrexate - Absorbed in jejunum. Labs:
Can be seen in : • 1-  Homocysteine
1- Alcoholism
- Small reserve pool stored primarily in the liver.
2- Normal methylmalonic acid
2- Pregnancy  Neural tube defects
Cofactor for : 1- Macrocytic, megaloblastic anemia
1- Homocysteine methyltransferase 2- Hypersegmented PMNCs
Vitamin B12 (cobalamin) (transfers CH3 groups as methylcobalamin) 3- Neurological Manifestation :
2- Methylmalonyl-CoA mutase A) Paresthesias
- Deficiency is usually caused by : B) Subacute combined degeneration
1- Insufficient intake (e.g., veganism) - Found in animal products Degeneration of :
2- Malabsorption : - Synthesized only by microorganisms - Dorsal columns
- Sprue - Lateral corticospinal tracts
- enteritis - Absorbed in terminal ileum
- Diphyllobothrium latum
- Spinocerebellar tracts
- Very large reserve pool (several years) stored primarily in liver.
3- Lack of intrinsic factor :  due to abnormal myelin.
- pernicious anemia: Labs:
Prolonged deficiency  irreversible nerve damage
"Anti-intrinsic factor antibodies" • 1-  Homocysteine
diagnostic for pernicious anemia. 2-  methylmalonic acid
- gastric bypass surgery
4- absence of terminal ileum:
- Crohn disease
 Genetics/Dysmorphology
Trisomy Syndromes
Down (Trisomy 21) Edward (Trisomy 18) Patau (Trisomy 13)
CNS 1- Mental Retardation 1- Mental Retardation 1- Holoprosencephaly
1- Brushfield spots 1- Microcephaly 1- Microcephaly
2- Upslanting palpebral fissure. 2- Micrognathia 2- Microophthalmia
Facial defects 3- Inner epicanthic folds 3- Prominent occiput 3- Ocular hypotelorism
4- Microganthis &Tongue protrusion 4- Low set malformed ears 4- Bulbous nose
5- Low set small ear 5- Low set malformed ears
6- Delayed fontanel closure 6- Cleft lip/palate
1- Hypotonia 1- Closed fist with : index finger
2- Simian crease overlapping the 3rd digit & 1- Flexed fingers
Extremities 3- short and broad hands 5th digit overlapping the 4th 2- with Polydactyly
4- Hypoplasia of the middle 2- Rocker bottom feet
phalanx of the 5th finger & Hammer toe
MedicoNotes provide high-yield USMLE notes , written professionally
Cardiac 1- Endocardial Cushion Defect (MOST COMMON)  lead to PH 1- VSD  MOST COMMON 1- VSD in tables over the
(major cause of early mortality) 2- VSD > PDA , ASD , MVP 2- ASD 3- PDA 2- ASD 3- PDA

usual long text-notes to help you study easily Omphalocele

GIT 1- Duodenal atresia 2- Esophageal atresia 3- Pyloric stenosis
4- Hirschbrung disease 5- Malrotation of bowel
and effectively. We summarized many
1- Polycystic kidney 1- Polycystic kidney
Renal
diseases in only few
1- Acute Lymphocytic Leukemia (ALL)
papers with tips &
2- Ectopictricks in
and double ureter diagnosis, differential diagnosis and
2- Early onset Alzheimer's disease Prognosis is Very poor, 95% die <1 year of age 1- Single umbilical artery
management to help
3- Atlantoaxial instability: ( 10% - 15%you recalling
Progress over several weeks)
- due to excessive laxity in the posterior transverse ligament 
the right answer immediately.
Complications causes increased mobility between atlas (C1) and the axis (C2) :

Our USMLE notes are written from confident sources and famous Question banks. We
a- Behavioral changes b- Torticollis c- urinary incontinence
d- Vertebrobasilarsymptoms : dizziness, vertigo, diplopia.
Risk factor: Advanced e- On examination, upper motor neuron symptoms such as :

help you not only to pass USMLE, but also to get high scores with our high yield notes.
maternal age >35 years leg spasticity, hyperreflexia, a positive Babinski sign, clonus
- X-ray: Diagnosed with lateral radiographs of the cervical spine
in flexion, extension, and in a neutral position
- TTT: surgical fusion of (C1) to the (C2).

To download
Turnerthe full file and
syndrome the other USMLE files, please
Sex Chromosome Abnormalities
Noonan syndrome click here
Klinefelter syndrome
(45XO or mosaicism) (47XXY)
Sporadic / Not related to advanced maternal age Not related to advanced maternal age Risk factor: Advanced maternal age

to SUBSCRIBE and get a lifetime membership.

Description
Phenotypically Female with :
1- Short stature
2- Craniofacial abnormalities: (protruding ears, neck webbing ,
low occipital hairline, high arched palate)
3- Endocrine: Primary Hypothyroidism
4- Chest: Shield shaped thorax / widely spaced nipples
5- Cardiac defects : Coarctation of the aorta + biscuspid aortic valve
6- Reproduction: Ovarian dysgenesis  Infertility
7- Renal Anomalies: Horseshoe Kidney, double renal pelvis (U/S)
Treatment: (give estrogen/ growth hormone / anabolic steroid)
Patients at higher risk of osteoporosis due to :
a- lower estrogen levels  ttt: give Estrogen
b- & only having one copy of X chr. genes involved in bone metabolism
- Autosomal dominant. - Presence of an extra X chromosome in males (1:500)
- Phenotypically similar to Turner syndrome but can affect both sexes. - Most common cause of hypogonadism and infertility in males
- Girls with Noonan syndrome have normal XX chromosomes. 1-Tall and thin body
- Pulmonary stenosis. 2- Gynecomastia + Female hair distribution
3- Testicular atrophy: Small testes but puberty occurs at normal age
- Mental retardation often present.
4- Azoospermia
5- Mild mental retardation + Psychosocial adjustment abnormalities
Diagnosis:
Testosterone levels: Hypogonadism & Hypogenitalism
Treatment:
Replace testosterone at 11-12 years of age

Common Deletion Syndromes

Prader-Willi Syndrome Angelman Syndrome Cri du chat Wolf-Hirschhorn Velocardiofacial Williams
Imprinting Disorders (different phenotype, same genotype) Deletion entire 5p chromosome arm Deletion 4p16 to end of arm Deletion 22q11 Deletion 7q11.23
Where the phenotype expression depends on whether the genetic defect is inherited from mother or father
75% due to Paternal deletion 15q11-13 60% due to Maternal deletion 15q11–13 1- Mentally: Mental Retardation 1- Mental retardation 1- Mild mental retardation 1- Mental retardation
Characteristic clinical features: Characteristic clinical features: 2- Microcephaly + there is a 2- Speech disorders 2- Cheerful/ friendly personality
2- Multiple cranial abnormalities
characteristic protruding metopic 3- Cleft palate 3- “Elfin facies”
1- Mentally: Mental retardation 1- Mentally: Mental Retardation 3- Seizures
suture in such patients. 4- Cardiac defects: TOF (short, upturned nose; long
2- Craniofacial features: 2- Absent speech or < 6 words
- Narrow bifrontal diameter 3- Happy mood 3- High-pitched cat-like cry philtrum, wide mouth)
5- Significant overbite
- Diamond-shaped eyes 4- Unprovoked laughter 4- Short stature
4- Other manifestations: 6- T-cell deficiency
- Small down-turned mouth "happy puppet Syndrome" 5- Cardiac defects
a- Hypotonia 7- Hypocalcemia
3- Hypotonia at birth or infancy 5- Ataxia. (supravalvular stenosis)
b- Short stature
4- Hyperphagia 6- Hypotonia 8- Association with DiGeorge
c- Moonlike face
5- Obesity (ataxia & hypotonia create the syndrome
d- Hypertelorism
6- Short stature + small hands & feet characteristic “puppet”-like gait)
e- Bilateral epicanthic folds Early mortality can result from
7- Hypothalamic dysfunctions : f- High arched palate associated :
- GH deficiency and g- Wide and flat nasal bridge 1- cardiac complications or
- Hypogonadotropic hypogonadism
80%  Develop Epilepsy
2- DiGeorge syndrome
TTT:
Short stature + obesity + hypotonia usually Detected by fluorescence in
respond to GH administration situ hybridization (FISH)

Other Syndromes
Fragile X syndrome - The syndrome results from: a ful lmutation in the FMR 1 gene caused by an increased number of CGG trinucleotide repeats accompanied by aberrant methylation of the FMR 1 gene.
Most common cause of Mental - Affected males of Fragile X syndrome have 3 LARGE : 1- Macrocephaly (Large Head)+ long face,prominent forehead 2- Large protruding ears 3- Large testes
Retardation in boys Behavioral: 1- Attention Deficit Hyperactivity Syndrome 2- Autism
- Infant with Multiorgan Enlargement: D.D: Congenital hypothyroidism
Beckwith-Wiedemann 1- Macrosomia 2- Macroglossia 3- Pancreatic B-cell hyperplasia: Hypoglycemia & Hyperinsulinemia Presents with :
syndrome 4- Visceromegaly 5- Omphalocele 5- Microcephaly 1- Hypotonia
- Usually sporadic BUT - Additional features include: 1- Prominent eyes 2- Prominent occiput 3- Ear creases 2- Macroglossia
- Some involving familial inheritance - Complications: 3- Umbilical hernia  Instead of omphalocele.
1- Hypoglycemia may be severe and intractable  TTT: subtotal pancreatectomy may be needed. 4- Head circumference of patients with congenital hypothyroidism may be increased
Associated with duplication of whereas patients with Beckwith syndrome have microcephaly.
chromosome 11 p (Encoding for IGF-2)
2- Patients have an increased risk of neoplasms such as: Wilms' tumor, Hepatoblastoma, Gonadoblastoma
- Obtain U/S & serum AFP every 6 months through 6 years of age to look for Wilm's Tumor/Hepatoblastoma 5- NO Hypoglycemia and hyperinsulinemia.
- Sporadic: defect in the G-prote in cAMP-kinase function in the affected tissue  thereby resulting in autonomous activity of that tissue.
McCune-Albright - It is a rare condition characterized by 3P: 1- Precocious puberty 2- Pigmentation: cafe au lait spots 3- Polyostotic fibrous dysplasia (multiple bone defects).
syndrome - It is responsible for 5% of the cases of female precocious puberty,
- may be associated with other endocrine disorders, as : 1- Hyperthyroidism, 2- Prolactin- or GH-secreting pituitary adenomas 3- Adrenal hypercortisolism.

Miscellaneous Autosomal Dominant Disorders

Osteogenesis imperfecta Marfan syndrome Ehlers-Danlos syndrome Myotonic muscular dystrophy (MMD)Steinert disease
- Caused by defect in type 1 collagen - Connective tissue disorders, caused by mutation of fibrillin-1 gene. It's a disorder of collagen structure. - Second most common muscular dystrophy in the United States.
- Patients have a weak bone matrix that leads to : - Clinical Features : - The pathologic distinct in that all types of muscles (i.e., smooth,
- Clinical Features :
1- Frequent fractures 1- Tall stature for age 2- Long face with crowded teeth striated, cardiac) are involved.
2- Bowing of the bones. 3- Long arm 4- Long thin fingers= Arachnodactyly ("spider fingers") - Clinical Features :
1- Hypermobile joints
- Types (4 types): 5- Sand legs. 6- Prominent sternum A)Patient initially appears normal at birth,  then slowly develops
2- Hyperelastic skin
All types can have : (1) Hypo : Hypotonia 3- Easy bruising Proximal muscle weakness and progressive muscle wasting :
1- Joint HYPERlaxity 2- HYPOtonia (2) Hyper: Hypermobilityof the joints & 4- Poor wound healing 1- Distal muscles of hands: atrophy of thenar & hypothenar
3- Early hearing loss 4- Wormian bones. Hyperelastic skin with diminished recoil 2- Posterior forearm muscle
(3) Cardiac: Aortic root dilatation (MR)  diastolic murmur Severe complications such as: 3- Anterior compartment of the lower legs
- Type II is the most severe form of OI and is usually lethal Ascending Aortic Dissection 1- Organ rupture B) Emaciated extremities, positiveGowers sign, winged scapula,
within the first year of life. Mitral Valve Prolapse 2- Severe hemorrhage may occur. and myotonia (delayed muscle relaxation)
- Types I, III, and IV can all be further categorized by the
(4) Ophthalmology: Iridodonesis from: Ectopia lentis / Lens dislocation C) Characteristic facial appearance :
presence or absence of dentinogenesis imperfect :
Myopia / blue sclera - Temporal wasting - Thin cheeks - Upper lip: inverted V shape
-- It's a disorder of tooth development (primary &
permanent teeth affected) Neurological: Dural ectasia D) Endocrine manifestations include :
-- The teeth are : discolored (bluish gray / yellow-brown), Progressive ectasia of the dura & neural foramina, and erosion of the - Diabetes mellitus - Testicular atrophy - Frontal baldness
translucent & weak. vertebral bone resulting consequently in enlargement of spinal canal. - Hypothyroidism.