1. Xeroderma pigmentosum
    Auto R. No nucleotide excision repair -- of thymidine dimers. Dry skin w/melanoma & other cancers.
  2. Adenosine deaminase deficiency
    Can't do adenosine --> inosine for purine breakdown, so adenosine goes back up to AMP --> nucleic acids: inhibits de novo nucleic acid synthesis. Most severe cause of SCID.
  3. DNA bond formation: the enzyme used & energy source
    DNA ligase. The 5' end of incoming nucleotide bears the triphosphate.
  4. Lesch-Nyhan syndrome
    Disorder of purine metabolism: mad because you can't "climb up the ladder." Absent HGPRT, so can't do hypoxanthine --> IMP or guanine --> GMP. Excess uric acid --> gout, aggression, retardation.
  5. Homocystinuria
    • Can't do homocysteine --> cystathionine (via cystathionine synthase), which eventually gives you cysteine.
    • Tall, hunchback man w/osteoporosis (but it's auto recessive inheritance) with lens subluxation, mental retardation, atherosclerosis.
  6. Cystinuria
    • Defective renal tubular transporters, so lots of cysteine excreted in urine (plus ornithine, lysine, & arginine).
    • Cysteine kidney stones; treat by alkalinizing urine.
  7. Maple syrup urine disease
    Deficient Alpha-ketoacid dehydrogenase, so no breakdown of branched-chain AA's (Isoleucine, Leucine, Valine = I Love Vermont maple syrup).

    Maple syrup-smelling urine, feeding problems/vomit, mental retardation, CNS deficits, death.
  8. Alkaptonuria
    • Black urine, CT, & pigmented sclerae; also, arthralgias. Usually asymptomatic until ~age 40!
    • Defective tyrosine breakdown, via homogentisic acid oxidase... so more tyrosine --> dopa --> melanin.
  9. Phenylketonuria
    • Defective phenylalanine --> tyrosine (done by phenylalanine hydroxylase). Eczema, fair skin, mental & growth retardation, musty body odor, seizures. Not observable right away at birth, but they do testing.
    • Tx: dec'd phenylalanine (in NutraSweet).
  10. Ornithine transcarbamoylase deficiency
    Can't do carbamoyl P + ornithine --> citrulline. X-linked recessive. Hyperammonemia sx (slurred speech, blurred vision, tremor, somnolence), plus excess carbamoyl P --> orotic acid in blood & urine.
  11. Albinism
    Tyrosine --> dopa --> melanin, so albinism = defective tyrosine transporter or tyrosinase. Can be due to lack of neural crest cell migration. Variable inheritance patterns, but ocular albinism = X-linked recessive.
  12. Urea cycle mnemonic
    Ordinarily, careless crappers are also frivolous about urination. (Aspartate = the first A)
  13. Orotic aciduria
    • Megaloblastic anemia. Causes of excess carbamoyl P:
    • 1) Urea cycle: ornithine transcarbamoylase deficiency: can't do carbamoyl P + ornithine --> citrulline, so excess carbamoyl P --> converted to orotic acid.
    • 2.) De novo pyrimidine synthesis: you're supposed to have carbamoyl P --> orotic acid, but then it's supposed to go orotic acid --> OMP --> UMP. Deficiency in orotic acid phosphoribosyltransferase or orotidine 5'-P decarboxylase.

    Difference between the 2: only #1 has hyperammonemia.
  14. Tay-Sachs disease
    • Hexosaminidase A deficiency --> accumulation of GM2 ganglioside in lysosomes.
    • Confusion, blind/deaf (cherry-red spots on macula), developmental delay, death by age 4-5. Lysosomes have onion-skinning.
  15. Niemann-Pick disease
    Blind/deaf (cherry-red spots on macula), hepatosplenomegaly (unlike Tay-Sachs). Sphingomyelinase deficiency in lysosomes, so sphingomyelinase accumulates. Foam cells w/zebra bodies, progressive neurodegeneration.
  16. The only 2 lysosomal storage diseases that aren't autosomal recessive
    Fabry's & Hunter's (both X-linked recessive)
  17. Fabry's disease
    Lots of organ systems: cardiovascular, renal, GI, peripheral neuropathy, eyes (angiokeratomas, corneal dystrophy). Deficient alpha-galactosidase A (think "alpha-males"); ceramide trihexoside accumulates. X-linked recessive inheritance.
  18. Gaucher's disease
    • The most common lysosomal storage disease. Bones: aseptic necrosis of femur, bone crises, Gaucher's cells (macrophages look like crumpled tissue paper = get gifts when you break bones). Hepatosplenomegaly, too. Almost all present in adulthood.
    • Deficient B- glucocerebrosidase. Accumulate glucocerebroside.
  19. Krabbe's disease
    Crabbiness = cerebral, so galactocerebrosidase deficiency (accumulate galactocerebroside). Peripheral neuropathy, optic atrophy, developmental delay, globoid cells.
  20. Metachromatic leukodystrophy
    • Demyelination -- both central & peripheral. Ataxia, dementia, death age 5-10.
    • Deficient arylsulfatase A, accumulate cerebroside sulfate.
  21. Aldose reductase
    Both glucose --> sorbitol and galactose --> galctitol... both cause eye probs.
  22. Glucogenic + ketogenic amino acids
    PITT: Phe, Isoleucine, Tryptophan, Threonine
  23. Ketogenic-only AA's
    Leucine, Lysine
  24. Alpha-ketoacid dehydrogenase
    Deficient in maple syrup urine disease (can't break down branched-chain AA's: ILV -- isoleucine, leucine, valine)
  25. Hurler's syndrome
    Airway obstruction, corneal clouding, gargoylism, developmental delay, hepatosplenomegaly. Enzyme deficient: alpha-L-iduronidase. Accumulated substrate: heparan & dermatan sulfate
  26. Hunter's syndrome
    Mild Hurler's + aggressive behavior & no corneal clouding. Deficiency of iduronate sulfatase. Accumulated heparan & dermatan sulfate.
  27. Rho protein
    • Helps to detach RNA polymerase from RNA after transcription ends.
    • RNA polymerase 1 = rRNA, 2 = mRNA, 3 = tRNA
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