Enzyme deficiency diseases

  1. PDH deficiency
    • Backup of alanine and pyruvate
    • Neurologic defects
    • Treat with ketogenic diet (fats, leucine/lysine)
  2. Pyruvate kinase deficiency
    Hemolytic anemia
  3. Chronic granulomatous disease
    • NADPH oxidase deficiency
    • Can't make ROS - no respiratory burst
    • Infection by catalase + organisms (S. aureus, aspergillus)
  4. G6PD deficiency
    • Don't make NADPH, can't reduce glutathione, can't maintain catalase
    • Free radials and peroxides in RBC cause hemolytic anemia
    • X-linked recessive
    • Heinz bodies, bite cells
  5. Methylmalonic aciduria
    • Can't convert to Succinyl-CoA
    • Can't metabolize odd-chain FAs
  6. Fructose intolerance
    • Aldolase B deficiency
    • Increased F-1-phosphate, decreased phosphate
    • Inhibition of glycogenolysis and gluconeogenesis
    • Hypoglycemia, jaundice, cirrhosis
  7. Essential fructosuria
    • Fructokinase defect
    • Benign, fructose in blood and urine
  8. Classic galactosemia
    • Absence of galactose-1-P uridyltransferase
    • Accumulation of galactitiol
    • FTT, jaundice, hepatomegaly, cataracts, mental retardation
    • Exclude galactose and lactose
  9. Galactokinase deficiency
    • Galactitol accumulates
    • Aldose reductase converts galactose to Galactitol
    • Mild, cataracts, galactose in blood and urine
  10. Ornithine transcarbamoylase deficiency
    • X-linked
    • Can't eliminate urea (can't make citrulline)
    • Carbamoyl phosphate converted to orotic acid (pyrimidine synthesis)
    • Ororic acid in blood and urine, decreased BUN, hyperammonemia
  11. Phenylketonuria
    • Phenylalanine hydroxylase deficiency or decreased BH4
    • Tyrosine becomes essential
    • Phenylketones in urine
    • Mental retardation, growth retardation, seizures, fain skin, ecaema, musty body odor (aromatic AAs)
    • Decrease phenylalanine, increase tyrosine
  12. Alkaptonuria/ochronosis
    • Deficiency of homogentisic acid oxidase
    • Can't degrade tyrosine
    • Dark connective tissue, pigmented sclera, urine turns black on standing (black as tyres)
  13. Albinism
    • Deficiency of tyrosinase or defective tyrosine transporters
    • Possibly from lack of migration of neural crest cells
  14. Homocystinuria
    • Excess homocysteine, cysteine becomes essential
    • Mental retardation, osteoporosis, tall stature, kyphosis, lens subluxation, atherosclerosis
    • Multiple causes:
    • Cystathione synthetase deficiency (give Met and Cys, B12 and folate)
    • Decreased affinity for pyridoxal phosphate (give B6 - pyridoxine)
    • Homocysteine methyltransferase deficiency
  15. Cystinuria
    • Defect of renal tubular amino acid transporter for cysteine, ornithine, lysine, and arginine in PCT
    • Cuases cystine kiney stones (staghorm)
    • Treat with acetazolamide to alkalinize urine
  16. Von Gierke's disease (Type I)
    • Deficiency of glucose-6-phosphatase (last step in glycogenolysis)
    • Severe fasting hypoglycemia, increased glycogen in liver, hepatomegaly, increased blood lactate (different from Cori's)
  17. Pompe's disease (Type II)
    • Lysosomal alpha-1,4-glucosidase
    • Cardiomegaly, early death
  18. Cori's disease (Type III)
    • Deficiency of debranching enzyme (alpha-1,6-glucosidase)
    • Fasting hypoglycemia, increased glycogen in liver, hepatomegaly, normal blood lactate
  19. McArdle's disease (Type V)
    • Defect in skeletal muscle glycogen phsophorylase (myophosphorylase)
    • Increased glycogen in muscle, but can't break it down
    • Muscle cramps, myoglobinuria with strenuous exercise
  20. Gaucher's disease
    • Deficiency of beta-glucocerebrosidase, accumulation of glucocerebroside
    • HSM, aseptic necrosis of femur, Gaucher's cells (macrophages that look like crumpled tissue papter)
  21. Niemann-Pick disease
    • Deficiency of sphingomyelinase, accumulation of sphingomyelin
    • Progressive neurodegeneration, HSM, cherry-red spot on macula, "foam cells"
  22. Tay-Sachs disease
    • Deficiency of hexosaminadase A, accumulation of GM2 ganglioside
    • Progressive neurodegeneration, developmental delay, cherry-red spot on macula, lysosomes with oncion skin, no HSM
  23. Krabbe's disease
    • Deficiency of galactocerebrosidase, accumulation of galactocerebroside
    • Peripheral neuropathy, developmental delay, optic atrophy, globoid cells
  24. Hurler's syndrome
    • Gargoylism, corneal clouding
    • Accumulation of heparan sulfate
  25. Hunter's syndrome
    Like Hurler's but w/o corneal clouding
  26. Carnitine deficiency
    • Inability to transport LCFAs into the mitochondria
    • Hypoketonic hypoglygemia, weakness, hypotonia
  27. Acyl-CoA dehydrogenase deficiency
    Increased dicarboxylic acids, decreased glucose and ketones
  28. Hyperchylomicronemia (Type I familial dyslipidemia)
    • LPL deficiency or altered apo CII
    • Increased blood chylomicrons, elevated TG and cholesterol
    • Pancreatitis, HSM, xanthomas
  29. Familial hypercholesterolemia (Type IIa familial dyslipidemia)
    • Absent or decresed LDL receptors
    • Accelerated atherosclerosis, tendon xanthomas, corneal arcus
    • Increased circulating LDL, high cholesterol
  30. Hypertriglyceridemia (Type IV familial dyslipidemia)
    • Hepatic overproduction of VLDL
    • Causes pancreatitis
    • Increased circulating VLDL, elevated TGs
  31. Abetalipoproteinemia
    • Deficiency of apo B100 and apo B48
    • AR
    • Accumulation of lipoproteins in enterocytes
    • FTT, steatorrhea, acanthocytosis, ataxia, night blindness
Card Set
Enzyme deficiency diseases
Enzyme deficiency diseases