Biochemistry Flashcards
LSD
Fabry Disease
- XLR Only LSD that is XLR all others are AR
- α-Galactosidase A Deficiency
- Globotriaosylceramide accumulated
- Angiokeratomas
- Peripheral neuropathy
- Glomerulopathy
LSD
Tay-sachs
AR
β-Hexosaminidase A deficiency
GM2 (ganglioside) accumulation
Macular cherry-red spot (Cherry Red Macula)
Progressive neurodegeneration
LSD
Gaucher Disease
- AR
- β-Glucocerebrosidase deficiency
- Glucocerebroside accumulation
- Hepatosplenomegaly
- Pancytopenia
- Bone pain/osteopenia
LSD
Niemann-Picks disease
- AR
- Sphingomyelinase Def
- Sphingomyelin accumulation
- Macular cherry-red spot
- Progressive neurodegeneration
- Hepatosplenomegaly (Not seen in tay-sachs)
LSD
Krabbe disease
- AR
- Galactocerebrosidase Def
- Galactocerebroside & psychosine accumulation
- Progressive neuro degeneration
- Peripheral neuropathy
- Optic atrophy
LSD
Metachromatic leukodystrophy
- AR
- Arylsulfatase A Def
- Cerebroside sulfate accumulation
- Progressive neurodegeneration
- Peripheral neuropathy
G6PD Deficiency
- Hemolytic anemia due to oxidative stress (infection, sulfa drugs, fava beans)
- X-linked: Asian, African, or Middle Eastern descent
- Pallor & fatigue
- Dark urine, jaundice & icterus
- Abdominal/back pain
- ↓ hemoglobin, ↓ haptoglobin,
- ↑ bilirubin & LDH, ↑ reticulocytes
- Bite cells & Heinz bodies
5-Alpha Reductase Def
- 46,XY genotype
- Impaired conversion of testosterone to DHT
- Male internal genitalia (eg, testes, vas deferens)
- Female external genitalia (eg, blind-ending vagina)
- Phenotypically female at birth
- Normal male testosterone & estrogen levels
- DHT promotes development of male external genetalia and prostate from genital tubercle and urogenital sinus
21 Hydroxylase Deficiency
- Increased 17-hydroxyprogesterone
- Increased testosterone
- Hypotension, Hyponatremia, and Hyperkalemia
- Low Cortisol and Aldosterone
- Low BP
17-Alpha hydroxylase deficiency
XY: atypical genitalia, undescended testes
XX: lacks 2° sexual development
the only one that presents with genital virilization in Males
Hypokalemia, Hypernatremia, Hyperglycemia
Di-George syndrome/velocardiofacial syndrome
Chromosome 22q11.2 deletion
Defective development of pharyngeal pouches (Defective neural crest migration into derivatives of the third and fourth pharyngeal pouches)
“CATCH-22”
C=Conotruncal cardiac defects (tetralogy of Fallot, truncus arteriosus, interrupted aortic arch)
A=Abnormal facies
T=Thymic hypoplasia/aplasia (T-cell deficiency)
C=Craniofacial deformities (cleft palate)
H=Hypocalcemia/Hypoparathyroidism
22=Chromosome
Fragile X Syndrome
CGG Trinucleotide Repeat
Intellectual disability
Prominent Forehead
Large Ears, Long Narrow Face, Prominent Chin
Macroorchidism
MCC of death is Cardiomyopathy.
Kartagner Syndrome
Immotile cilia due to AR microtubular defect in dynein arm (dyenin powers intracellular vesicle transport).
Patients present as:
- Infertility
- Situs inversus
- Chronic sinusitis
- Bronchiectisis
Friedreich ataxia
Autosomal recessive
FXN gene mutation GAA trinucleotide repeat
Staggering gait, frequent falls, nystagmus, hammer toes, diabetes mellitus, hypertrophic cardiomyopathy
MCC of death in patient is Hypertrophic cardiomyopathy
Leukocyte adhesion deficiency
(type 1; defective LFA-1 integrin)
Late separation (>30 days) of umbilical cord, No pus, Recurrent skin and mucosal bacterial infections.
Chronic granulomatous disease
(defect of NADPH oxidase)
Neutrophils lack respiratory burst
Recurrent infections and granulomas with catalase ⊕ organisms
(Staph Aureus, Burkholderia cepacia, serratia marceanes, Nocardia)
Fungi: Aspergillus
Dx: DHR (Dihydrorhodamine test)
NBT (Nitroblue tetrazolium)
Alkaptonuria
(homogentisate oxidase deficiency; ochronosis)
Bluish-black connective tissue, ear cartilage, sclerae ( Homogentisic Acid accumulation)
urine turns black on prolonged exposure to air
Phenylketonuria
AR : PKU gene mutation
Defective phenylalanine hydroxylase
Phenylalanine can’t be converted to tyrosine
Intellectual disability, Microcephaly, Movement disorders, musty body odor, hypopigmented skin, eczema.
Increase Tyrosine in diet, restrict phenylalanine in diet.
Homocystinuria
AR
Deficinecy of Cystathione Beta Synthase
Vitamin B6 (Pyridoxine) dependant
Accumulation of Homocystiene, Defective conversion of homocystine to Cystiene.
Arachnodactyly, pectus deformity, lens dislocation (downward)
Sometimes respond to Vit-B6 (pyridoxine)
Lesch-Nyhan syndrome
(HGPRT deficiency, XLR)
Gout, intellectual disability, self-mutilating behavior in a boy.
“ H G P R T “
H = Hyperurecemia
G = Gout
P = Pissed off (aggressive/ self mutilating)
R = Retardation
T = Tone decreased (Dystonia)
Hereditary fructose
intolerance
Hereditary deficiency of aldolase B
Fructose-1-phosphate accumulates, inhibition of glycogenolysis and gluconeogenesis
Symptoms present following consumption of fruit, juice, or honey
hypoglycemia, jaundice, cirrhosis, vomiting.
Galactokinase
deficiency
Hereditary deficiency of galactokinase.
Galactitol accumulates
galactose appears in blood (galactosemia) and urine (galactosuria); infantile cataracts.
May present as failure to track objects or to develop a social smile.
Classic galactosemia
Absence of galactose-1-phosphate uridyltransferase.
accumulation of toxic substances (including galactitol, which accumulates in the lens of the eye)
Symptoms develop when infant begins feeding
failure to thrive, jaundice, hepatomegaly, infantile cataracts, intellectual disability
Lactase deficiency
Insufficient lactase enzyme > dietary lactose intolerance.
Lactase functions on the intestinal brush
border to digest lactose (in milk and milk products) into glucose and galactose.
Bloating, cramps, flatulence (all due to fermentation of lactose by colonic bacteria –> gas), and
osmotic diarrhea (undigested lactose).
Hyperammonemia
flapping tremor (asterixis), slurring
of speech, somnolence, vomiting, cerebral
edema, blurring of vision.
CNS toxicity
may involve GABA, α-ketoglutarate, TCA
cycle inhibition, and cerebral edema due to
glutamine-induced osmotic shifts.
Ornithine
transcarbamylase
deficiency
XLR
Excess carbamoyl phosphate is converted
to orotic acid (part of the pyrimidine synthesis pathway).
Inc orotic acid in blood and urine, Dec BUN, symptoms of hyperammonemia.
No megaloblastic anemia (vs orotic aciduria).
Maple syrup urine
disease
Blocked degradation of branched amino acids
(Isoleucine, leucine, valine) due to Decrse branched-chain α-ketoacid dehydrogenase (B1).
vomiting, poor feeding, urine
smells like maple syrup/burnt sugar, progressive neurological decline
Cystinuria
Hereditary defect of renal PCT and intestinal amino acid transporter that prevents reabsorption of Cystine, Ornithine, Lysine, and Arginine (COLA).
Excess cystine in the urine can lead to recurrent
precipitation of hexagonal cystine stones.
GSD
Von Gierke disease
(type I)
Glucose-6-phosphatase Deficiency
Severe fasting hypoglycemia,
Incrse Glycogen in liver and
kidneys, Incrse triglycerides, Incrse Uric Acid.
Gout, Hepatomegaly,
Renomegaly.
Von-Gierke= 3 G
Glycogen in liver, G6P, Gout
Impaired gluconeogenesis and
glycogenolysis.
GSD
Pompe disease
(type II)
Lysosomal acid α-1,4-
glucosidase (acid maltase) Deficiency
Cardiomegaly, Hypotonia, Enlarged tongue.
GSD
Cori disease
(type III)
Debranching enzymes
(α-1,6-glucosidase and
4-α-d-glucanotransferase) Deficiency.
Similar to von Gierke disease,
Gluconeogenesis is intact.
GSD
Andersen disease
(type IV)
Branching enzyme Deficiency.
hepatosplenomegaly
and failure to thrive in early
infancy.
GSD
McArdle disease
(type V)
Skeletal muscle glycogen
phosphorylase
(myophosphorylase) deficiency,
Incrse glycogen in muscle
painful muscle cramps,
myoglobinuria (red urine), Weakness & fatigue w exercise
no rise in lactate levels after exercise
LSD Mucopolysaccharidosis
Hurler syndrome
AR
α-l-iduronidase deficiency.
Heparan sulfate, dermatan sulfate accumulation
Developmental delay, skeletal
abnormalities, airway obstruction,
corneal clouding, hepatosplenomegaly
LSD Mucopolysaccharidosis
Hunter Syndrome
XLR
Iduronate-2 (two)-
sulfatase deficiency.
Heparan sulfate, dermatan sulfate accumulation.
Mild Hurler + aggressive behavior, no corneal clouding.
“Hunters see clearly (no corneal clouding) and aggressively aim for the X (X-linked recessive)”
Metabolic Fuel Breakdown
1g carb/protein = 4 kcal
1g alcohol = 7 kcal
1g fatty acid = 9 kcal
LSD
I-cell disease
Aka inclusion disease
N-acetyl glucosamine 1 phosphate
Sphingolipid and mucoploysachride accumulation in lysosomes
Corneal clouding
Failure to thrive
Hyperlipidemias
Familial Chlyomicronemia (type-1)
Lipoprotien lipase defect
Increase Chylomicrons
P/E
Acute pancreatitis
Lipemia retinalis
Erouptive xanthomas
Hyperlipidemias
Familial Hypercholestrolemia (type-2)
LDL receptor defect
Increase LDL
P/E
Tendon xanthomas
Xanthelesmas
Premature atherosclerosis
Hyperlipidemias
Familal dysbetalipidemia (type-3)
Apo E defect
Increase Chylomicrons & VLDL
P/E
Premature atherosclerosis
Xanthomas
Hyperlipidemias
Familial Hypertriglycerdiemia (type-4)
Polygenic
Increase VLDL
P/E
Coronary artery disease
Pancreatitis
Diabetes mellitis
Anticholinestrase poisoning
Aka Organophosphate poisoning
Irreversible inhibition of acetylcholinesterase
Symptoms include:
Vomitting, Diarrhea, Diaphoresis, Urination, Lacrimation, Salivation, Bronchorrea, Bronchospasm, Bradycardia, Siezures, Muscle weakness
Responsible toxins are:
Parathoin , Fenthoin , Malathoin.
Tx:
Atropine : antagonizes muscranic receptors.
Pralidoxime : Regenerate function AchE.
Celiac disease
Intolerence to Gluten ( i.e gliadin protiens found in wheats, oats, rye and barley, but not in rice )
Causes Type-IV hypersenstivity response where T-cells attack the small intestinal villi, resulting in flattening of villi and malabsorbtion.
Anti-Endomysial ( AKA Anti-Gliadin ) antibody
Anti-Tissue Transglutaminase IgA
Patients with IgA deficiency have greater chance of developing celiac disease
Celiac disease present as vague bloating and diarrhea but can also cause Iron Def Anemia as iron absorbtion is impaired by flattening of villi.
Celiac disease has low Hb ( HY differential )
D-xylose test is abnormal as intestinal lining architecture is abnormal.
Assossiated with dermatitis herpitiformis and also cause increased risk of gastrointestinal T-cell Lymphoma ( Enteropathy- Assosiated T-cell Lymphoma EATL )
Alport Syndrome
X-Linked disease:
- Mutation in collagen IV gene
- Patient who has red urine + eye or ear problem.
- Collagen IV is present in basement membrane of kidney, ear, eyes.
- Eye problems can be blurry vision/ cataracts
- Ear problems will be neurosensory hearing loss due to organ of corti dysfunction.
Chediak-Higashi syndrome
LYST gene : Defect in microtubule function.
Presents as;
“ C A I N “ C = Coagulopathy. A = Albinism. I = Infections. N = Neuropathy.
Glycolysis
Cri-du-chat (cry of the cat) syndrome
Microcephaly, high-pitched cry, intellectual disability
Edwards syndrome
(trisomy 18)
Miotic Non-disjunction
Infant with microcephaly, rocker-bottom feet, clenched hands, and structural heart defect (VSD)
“ P R I N C E edward “
P = Prominent Occiput
R = Rocker Bottom Feet
I = Intellectual disability
N = Non-disjunction
C = Clenched fist , Cardiac abnormality (VSD)
E = Eighteen Chromosome
Patau syndrome
(trisomy 13)
Infant with cleft lip/palate, microcephaly or
holoprosencephaly, polydactyly, cutis aplasia
“ C R A M P “
C = Cleft lip
R = Renal abnormality
A = Abnormal heart
M = Mental retardation, Microcephaly
P = Polydactyly.
Duchenne muscular dystrophy
XLR
Mutation in DMD gene encoding Dystrophin, a cytoplasmic protien that plays imp role in anchoring muscle Actin filament to plasma membrane
(Gowers sign)
Child uses arms to stand up from squatting postion,
Weakness of lower limb girdle
Proximal muscle weakness after a period of relatively normal development.
Complication include dilated cardiomyopathy and respiratory insufficiency
Abnormal protien accumulated in cytoplasm.
Becker muscular dystrophy
(X-linked non-frameshift deletions in dystrophin; less severe than Duchenne)
Slow, progressive muscle weakness in boys
McCune-Albright syndrome
(Gs-protein activating mutation)
Café-au-lait spots (unilateral), polyostotic fibrous dysplasia, precocious puberty, multiple endocrine abnormalities
Li-Fraumeni syndrome
TP53 Mutation
Autosomal dominant
Caused by inactivating mutation in corresponding tumor suppressor gene
Deletion of remaining normal allele (second hit) leads to loss of heterozygosity & malignant transformation
Sarcomas, Breast cancer, Brain tumors, Adrenocortical carcinoma, Leukemia
Fragile X Syndrome
CGG Trinucleotide Repeat
Intellectual disability
Prominent Forehead
Large Ears, Long Narrow Face, Prominent Chin
Macroorchidism
MCC of death is Cardiomyopathy.
Turner syndrome (45,XO)
Streak ovaries, congenital heart disease, horseshoe kidney,
cystic hygroma, short stature, webbed neck, lymphedema
Edwards syndrome
(trisomy 18)
Miotic Non-disjunction
Infant with microcephaly, rocker-bottom feet, clenched hands, and structural heart defect (VSD)
“ P R I N C E edward “
P = Prominent Occiput
R = Rocker Bottom Feet
I = Intellectual disability
N = Non-disjunction
C = Clenched fist , Cardiac abnormality (VSD)
E = Eighteen Chromosome
Patau syndrome
(trisomy 13)
Infant with cleft lip/palate, microcephaly or
holoprosencephaly, polydactyly, cutis aplasia
“ C R A M P “
C = Cleft lip
R = Renal abnormality
A = Abnormal heart
M = Mental retardation, Microcephaly
P = Polydactyly.
Ehlers-Danlos syndrome
(type V collagen defect, type III collagen defect seen in vascular subtype of ED)
Elastic skin, hypermobility of joints, Inc bleeding tendency.
Osteogenesis imperfecta
(type I collagen defect)
Blue sclera, multiple fractures, dental problems,
conductive hearing loss
Wilsons Disease
AR, Chromosome 13
- Defective Copper transport protien ATP7B.
- Impaired biliary excretion of Copper accumulation of Cu in hepatocytes cause oxidative stress and apoptosis (Cirrhosis).
- Extra hepatic Cu accumulation in basal ganglia (Encephalopathy), Cornea (Kayser-Fischer Ring).
Classical Symptoms Traid:
1-Hepatic (Cirhosis, Liver failure)
2-Neurological (Confusion, Disorientation)
3-Psycological (Depression)
Parkinsonism in young patient is Wilson disease.
Putamen in brain is damaged in wilson disease.
Tx: Penicillamine ( Copper chelator )
Sturge-weber syndrome
- Cutaneous Angioma over head & neck (Portwine stain).
- Focal/ generalized siezures.
- Hemiparesis.
- Intellectual disability.
Kids go on to develop Glaucoma.
Tuberous Sclerosis
AD mutation in Hamartin gene (chromosome 9) or Tuberin gene (chromosome 16).
- Hamartomas (can present anywhere in body).
- Siezures.
- Psychomotor delay.
- Intellectual disability.
- Adenoma sebaceum.
- Ash-leaf spot & Shagreen patches.
Also assosiated with kidney tumors known as Renal angiomyolipomas and heart tumor i.e Cardiac rhabdomyoma.
Chediak-Higashi syndrome
LYST gene : Defect in microtubule function.
Presents as;
“ C A I N “ C = Coagulopathy. A = Albinism. I = Infections. N = Neuropathy.
Cystic Fibrosis
- Autosomal recessive mutation (∆F508) impairs - - CFTR function
- ATP dependant Chloride channel defective
- Chronic, productive cough
- Recurrent sinopulmonary infections (eg,Staphylococcus aureus, Pseudomonas aeruginosa)
- Pancreatic insufficiency (Def Fat Sol Vitamins)
- Male infertility (bilateral absence of vasdeferens)
- Elevated sweat chloride levels
Hartnup Disease
AR
Inactivating mutation effecting transport of neutral amino acids. Particularly Tryptophan which is a precursor for Niacin, Serotonin & Melatonin.
Present with pllegra like skin erouptions (Rash following sun exposure)
Cerebellar Ataxia
Niacin Deficiency
Neutral Aminoaciduria (Alanine, serine, threonine, valine, leucine, isoleucine, phenylalanine, tyrosine & tryphtophan)
Primary Carnitine Deficiency
- Myopathy (eg, elevated creatine kinase, weakness),
- Cardiomyopathy (eg, S3 gallop),
- Hypoketotic hypoglycemia (eg, absence of ketones in the urine)
- Decreased muscle carnitine
- Patient has deficient synthesis of Acetoacetate
