shosh: diseases in biochem

  1. Pyruvate kinase deficiency
    • Most common glycolytic enzyme deficiency
    • Causes hemolytic anemia, since inability to maintain Na/K pump leads to RBC swelling and lysis
  2. Pyruvate dehydrogenase deficiency
    • Inability to synthesize acetyl CoA from pyruvate and alanine causes buildup of substrates, and lactic acidosis
    • Seen in alcoholics, due to B1 (thiamine) deficiency
    • Neurological deficits
  3. G6PD deficiency
    • Hemolytic anemia, due to oxidative stress (antimalarials, sulfonamides, infection)
    • X-linked
    • Oxidized Hb precipitates in RBCs, and forms Heinz bodies
    • Bite cells on peripheral smear
  4. Fructose intolerance
    • Aldolase B deficiency
    • Accumulation of fructose-1P inhibits glycogenolysis and gluconeogenesis
    • Symptoms include hypoglycemia, jaundice, cirrhosis, and vomiting
    • Appears in babies, when they start eating fructose
  5. Essential fructosuria
    • Fructokinase deficiency
    • Fructose appears in blood and urine
    • Benign
  6. Classic galactosemia
    • Galactose 1P uridyltransferase deficiency
    • Toxins accumulate in eye and neurons
    • Symptoms include failure to thrive, jaundice, hepatomegaly, infantile cataracts, and retardation
  7. Ornithine transcarbamoylase deficiency
    • Most common defect in the urea cycle
    • X-linked
    • Excess carbamoyl phosphate is converted into orotic acid, which builds up in the blood and urine
    • Decreased BUN
    • Ammonia intoxication
  8. Phenylketonuria
    • Phenylalanine hydroxylase or tetrahydrobiopterin deficiency
    • Phenylalanine cannot be converted into tyrosine, making tyrosine and essential AA
    • Presents with mental retardation, growth retardation, seizures, albinism (lack of melanin), eczema, and a musty body odor
  9. Alkaptonuria
    • Homogentisic acid oxidase deficiency causes impaired tyrosine degradation
    • Findings include dark CT, pigmented sclera, urine that blackens in the air
    • Arthralgias
  10. Sorbitol accumulation
    Aldose reductase converts glucose to sorbitol, which accumulates in cells and causes osmotic damage (re: cataracts, retinopathy, peripheral neuropathy, seen in diabetes)
  11. Albinism
    Can be due to a tyrosinase deficiency (tyrosine is converted to melanin) or a failure of neural crest cells to migrate
  12. Homocystinuria
    • Can be due to a deficiency in B6, B12, or folate
    • Can be due to a mutation in cystathione synthase or homocysteine methyltransferase
    • Causes mental retardation, osteoporosis, kyphosis, lens subluxation, and atherosclerosis
  13. B12 deficiency
    • B12 is needed to activate folate and to convert methylmalonyl CoA to succinyl CoA
    • Lack of active folate causes megaloblastic anemia
    • Buildup of methylmalonyl CoA causes peripheral neuropathy
  14. Cystinuria
    • Caused by an AR defect in the renal cysteine transporter
    • Cystine buildup precipitates as stones
    • Treat with acetazolamide to alkalinize urine (since cystine is more soluble at high pH)
  15. Maple syrup urine disease
    • Due to a defect in branched amino acid dehydrogenase
    • Buildup of isoleucine, leucine, and valine
    • Severe CNS defects and death
  16. Hartnup disease
    • Defective tryptophan reabsorption in urine
    • Causes pellagra like symptoms (diarrhea, dermatitis, dementia), since tryptophan is used to make niacin
  17. Von Gierke's disease (type I)
    • Deficient glucose 6 phosphatase
    • Severe fasting hypoglycemia and hepatomegaly
    • Doll-like facies
    • Hyperlipidemia
    • Increased blood lactate
  18. Pompe's disease (type II)
    • Deficient lysosomal a-1,4 glucosidase
    • Cardiomegaly
  19. Cori's disease (type III)
    • Deficient debranching enzyme
    • Glycogen looks abnormal under a microscope, but little or no hypoglycemia
  20. McArdle's disease (type V)
    • Deficient glycogen phosphorylase in skeletal muscle
    • Cramps and myoglobinuria after exercise
  21. Hers disease (type VI)
    • Deficient glycogen phosphorylase in the liver
    • Hepatomegaly
    • Mild hypoglycemia (gluconeogenesis is intact)
  22. Fabry's disease
    • Deficient a-galactosidase A
    • XR
    • Peripheral neuropathy
    • Angiokeratomas
    • Cardiovascular and renal disease
  23. Gaucher's disease
    • Deficient B-glucocerebrosidase
    • Hepatosplenomegaly
    • Aseptic necrosis of head of femur
    • Crumpled tissue paper macrophages
  24. Neimann-Pick disease
    • Deficient sphingomyelinase
    • Progressive neurodegeneration
    • Hepatosplenomegaly
    • Cherry-red spot on macula
    • Foam cells
  25. Tay-Sachs disease
    • Deficient hexosaminidase A
    • Progressive neurodegeneration
    • Cherry-red spot on macula
    • NO hepatomegaly
  26. Krabbe's disease
    • Deficient galactocerebrosidase
    • Peripheral neuropathy
    • Optic atrophy
    • Globoid cells
  27. Metachromatic leukodystrophy
    • Deficient arylsulfatase A
    • Central and peripheral demyelination, with ataxia and dementia
  28. Hurler's syndrome
    • Deficient a-L-iduronidase
    • Gargoylism
    • Airway obstruction
    • Corneal clouding
    • Hepatosplenomegaly
    • (Hunter's syndrome is like Hurler's, but more mild, and XR, with no corneal clouding)
  29. Abetalipoproteinemia
    • Inability of enterocytes to form chylomicrons
    • Decreased TGs, cholesterol, and FAs
    • Acanthocytes
    • Steatorrhea
    • Night blindness
  30. Type I hyperchylomicronemia
    • Defective lipoprotein lipase or ApoC-II (activates LPL
    • Pancreatitis, hepatosplenomegaly, xanthomas
    • NO increased risk for atherosclerosis
  31. Type II familial hypercholesterolemia
    • Deficient LDL receptors
    • AD
    • Accelerated atherosclerosis (homozygotes die of heart failure by 20)
    • Corneal arcus
  32. Type IV hypertriglyceridemia
    • Hepatic overproduction of VLDLs
    • Pancreatitis
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shosh: diseases in biochem