MCP Diseases Flashcards
Tay-Sachs Disease
-beta-hexosaminidase A (alpha subunit) deficiency -gangliosides accumulate
Gm: Gangliosidosis
- beta-galactosidase deficiency
- gangliosides and keratin sulfate accumulate
Gaucher Disease
- beta-glucosidase (glucocerebrosidase) deficiency
- glucocerebrosides accumulate
Metachromatic leukodystrophy
- arylsulfatase A deficiency
- sulfatides accumulate
Krabbe disease
- beta-galactocerebrosidase (galactocerebrosidase) deficiency
- galactocerebrosides accumulate
Farber disease
- ceraminidase deficiency
- ceramide accumulates
Niemann-Pick disease
- sphingomyelinase deficiency
- sphingomyelin accumulates
Fabry disease (X-linked)
- alpha-galactosidase deficiency
- globosides accumulate
Sandhoff disease
- beta-hexosaminidase A (beta-subunit) &B
- GM2/globosides accumulate
Zellweger Syndrome
- lack of functional peroxisomes
- DHAP–>ethanolamine rxn can’t occur, since the rxn takes place in peroxisomes
Homocystinuria
- cystathionine synthase deficiency
- rapidy accelerated atheroschlerosis, mental retardation
Cystathioninuria
- cystathionase deficiency
- accelerated atheroschlerosis
Pernicious/Megaloblastic anemia
- THF/cobalamin deficiency
- immature RBCs in circulation
- cobalamin deficiency also causes demyelination/degeneration of spinal cord
Folate trap
- cobalamin deficiency
- homocysteine builds up since THF/cobalamin can’t convert it back to methionine (THF still stuck in 5-methyl form)
- neurological problems without anemia
Ammonia toxicity
- brain glutamate deficiency (alpha-ketoglutarate is used to make glutamate)
- low levels of GABA/high tryptophan conversion to serotonin
- uncontrolled NT levels in the brain
Maple syrup urine disease, branched chain ketoaciduria
- branched-chain keto acid dehydrogenase (same enzyme converts alpha-ketos of valine, leucine, isoleucine)
- keto acid builds up in pee and makes it smell like maple syrup (da fuck?)
phenylketonuria
- phenylalanine hydroxylase deficiency
- phenylalanine can’t be converted into tyrosine tyrosine become an essential amino acid phenylalanine derivatives build up, many are neurotoxic
alkaptonuria
- homogentisate oxidase deficiency
- homogentisic acid can’t be converted into 4-maleyl-acetoacetic acid (same steps as phenylalanine/tyrosine metabolism)
- symptoms are dark urine and sometimes arthritis from build-up (can be diagnosed by looking at ear lobes with a light)
tryptophan deficiency (pellagra)
4 Ds: diarrhea, dementia, dermatitis, death (origin of redneck!)
Cystic fibrosis
- improper folding of CFTR Cl- channels
- pancreatic enzyme deficiency (among other symptoms)
Hartnup’s disease, similar to pellagra
- neutral/aromatic amino acids can’t be transported from gut/renal tubules
- 4 Ds
cystinuria
- basic amino acids/cysteine can’t be transported from gut/renal tubules
- cysteine forms crystals, causes UTIs/kidney stones
Arginosuccinic aciduria (ammonia intoxication)
- arginosuccinase deficiency
- NH4/arginosuccinic acid in blood
- arginosuccinic acid in urine
- normal intelligence
Hyperammoniemia (ammonia intoxication)
- carbamoyl phosphate synthase deficiency
- high NH4 in blood
- normal intelligence
Arginiemia (ammonia intoxication)
- arginase deficiency
- high NH4, arginine in blood
- Arg, Lys, ornithine in urine
- normal intelligence
Citrullinemia (ammonia intoxication)
- argininosuccinate synthetase
- high NH4, citrulline in blood
- citrulline in urine
- mental retardation
Hyperornithinemia (ammonia intoxication)
- ornithine transcarbamylase
- high NH4, orotate, ornithine in blood
- ornithine in urine
- normal intelligence
Smith-Lemli-Opitz Syndrome
- 7-dehydrocholesterol-7-reductase deficiency
- impaired cholesterol synthesis
Type I Hyperlipoproteinemia, familial LPL deficiency
- LPL or ApoCII deficiency
- accumulate chylomicron TAGs in plasma
- higher pancreatitis risk
Non-alcoholic fatty liver (hepatic steatosis)
- imbalance between TAG synthesis and VLDL secretion
- liver stuff??
Familial type III hyperlipoproteinemia
- can’t clear chylomicrons or IDL
- hypercholesterolemia and premature atheroschlerosis
Familiar hypercholesterolemia (FH), type II hyperlipidemia
- deficiency of LDL receptor LDL-R
- elevated plasma cholesterol
Tangier disease
- ABCA1 deficiency (whatever that does)
- absence of HDL, since lipid-free apo A1 degraded
3-beta-hydroxysteroid deficiency
- pregnenolone builds up, can’t be converted to progesterone
- pretty much no mineralocorticoids, glucocorticoids, androgens, estrogens (since 1st step in further synthesis blocked)
17-alpha-hydroxylase deficiency
- 17-alpha-hydroxylase allows androgen/cortisol precursor synthesis
- with deficiency, progesterone only follows aldosterone pathway (opposite of 21 pathway)
- only mineralocorticoids synthesized, no sex hormones or cortisol
21-alpha-hydroxylase deficiency
- 21-alpha-hydroxylase allows mineralocorticoid and glucocorticoid synthesis
- with deficiency, mineralocorticoids/glucocorticoids absent (opposite of 17 pathway)
- too many androgens!
11-beta1-hydroxylase deficiency
- corticosterone can’t form, so neither can cortisol or aldosterone
- too many androgens (resembles 21 deficiency)
Ricketts (vit D deficiency)
- kids have enough collagen matrix, but not enough mineralization; bones become curvy, soft
- prophylactic supplements early on for Rx?
Osteomalacia
- bones made already, become demineralized; fractures common
- prophylactic vit D?
renal osteodystrophy (consequence of chronic renal disease)
- not enough active synthesis of vit D (remember, kidney helps convert it to its active form too!)
- hypocalcemia and hyperphosphatemia
- give calcitrol and reduce dat phosphate
Hyperthyroidism
- no PTH at all
- hypocalcemia and hyperphosphatemia
- calcium and calcitrol
Orotic aciduria
- orotic acid builds up in blood, excreted in urine
- give uridine or cytidine, gives body needed pyrimidine bases and inhibits CPH
Gout
- excess uric acid causes precipitation of sodium urate crystals in joints of extremities
- macrophages eat them, then rupture-inflamm process starts
- either an abnormal PRPP synthase (not responsive to inhibition by purine nucleoside diphosphates) or partial HGPRT deficiency (causes increased PRPP and purine synthesis)
- oxypurinol suicide inhibitor of xanthine oxidase or allopurinol to block uric acid production
Lesch-Nyhan Syndrome (XLR)
- severe or complete HGPRT deficiency
- too many purines made, also PRPP increases (bad double whammy)
- gout, hyperuricemia, self-mutilation, neurological disturbances
- try allopurinol to reduce uric acid formation, but symptoms irreversible
Adenosine deaminase (ADA) deficiency, combined with severe combined immunodeficiency (SCID)
- too much deoxyadenosine and adenosine can’t be broken down into deoxyinosine and inosine
- high levels of dATP inhibit ribonucelotide reductase so DNA synthesis inhibited, leuks can’t multiply
- BM transplants, gene therapy
medium-chain acyl-Coa dehydrogenase (MCAD) deficiency
- octanylcarnithine accumulates, thought to be toxic
- usually no symptoms until hypoglycemia, then rapid progression
- treat by avoiding fasting and low-fat/high-carb diet
Lactose Intolerance
-lactase (beta-galactosidase) deficiency and associated symptoms
Von-Gierke Disease (glycogen storage disease)
- G6P or transport system defective
- glycogen buildup in liver and kidney
- failure to thrive
Anderson Disease
- alpha 1,4–>alpha 1,6 defective
- liver and spleen affected
- normal amount of glycogen, but long outer branches
- early progressive cirrhosis
McArdle Disease
- phosphorylase defective
- skeletal muscle affected
- limited ability to perform strenuous exercise, otherwise patient ok
