-
PDH deficiency
- Backup of alanine and pyruvate
- Neurologic defects
- Treat with ketogenic diet (fats, leucine/lysine)
-
Pyruvate kinase deficiency
Hemolytic anemia
-
Chronic granulomatous disease
- NADPH oxidase deficiency
- Can't make ROS - no respiratory burst
- Infection by catalase + organisms (S. aureus, aspergillus)
-
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
-
Methylmalonic aciduria
- Can't convert to Succinyl-CoA
- Can't metabolize odd-chain FAs
-
Fructose intolerance
- Aldolase B deficiency
- Increased F-1-phosphate, decreased phosphate
- Inhibition of glycogenolysis and gluconeogenesis
- Hypoglycemia, jaundice, cirrhosis
-
Essential fructosuria
- Fructokinase defect
- Benign, fructose in blood and urine
-
Classic galactosemia
- Absence of galactose-1-P uridyltransferase
- Accumulation of galactitiol
- FTT, jaundice, hepatomegaly, cataracts, mental retardation
- Exclude galactose and lactose
-
Galactokinase deficiency
- Galactitol accumulates
- Aldose reductase converts galactose to Galactitol
- Mild, cataracts, galactose in blood and urine
-
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
-
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
-
Alkaptonuria/ochronosis
- Deficiency of homogentisic acid oxidase
- Can't degrade tyrosine
- Dark connective tissue, pigmented sclera, urine turns black on standing (black as tyres)
-
Albinism
- Deficiency of tyrosinase or defective tyrosine transporters
- Possibly from lack of migration of neural crest cells
-
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
-
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
-
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)
-
Pompe's disease (Type II)
- Lysosomal alpha-1,4-glucosidase
- Cardiomegaly, early death
-
Cori's disease (Type III)
- Deficiency of debranching enzyme (alpha-1,6-glucosidase)
- Fasting hypoglycemia, increased glycogen in liver, hepatomegaly, normal blood lactate
-
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
-
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)
-
Niemann-Pick disease
- Deficiency of sphingomyelinase, accumulation of sphingomyelin
- Progressive neurodegeneration, HSM, cherry-red spot on macula, "foam cells"
-
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
-
Krabbe's disease
- Deficiency of galactocerebrosidase, accumulation of galactocerebroside
- Peripheral neuropathy, developmental delay, optic atrophy, globoid cells
-
Hurler's syndrome
- Gargoylism, corneal clouding
- Accumulation of heparan sulfate
-
Hunter's syndrome
Like Hurler's but w/o corneal clouding
-
Carnitine deficiency
- Inability to transport LCFAs into the mitochondria
- Hypoketonic hypoglygemia, weakness, hypotonia
-
Acyl-CoA dehydrogenase deficiency
Increased dicarboxylic acids, decreased glucose and ketones
-
Hyperchylomicronemia (Type I familial dyslipidemia)
- LPL deficiency or altered apo CII
- Increased blood chylomicrons, elevated TG and cholesterol
- Pancreatitis, HSM, xanthomas
-
Familial hypercholesterolemia (Type IIa familial dyslipidemia)
- Absent or decresed LDL receptors
- Accelerated atherosclerosis, tendon xanthomas, corneal arcus
- Increased circulating LDL, high cholesterol
-
Hypertriglyceridemia (Type IV familial dyslipidemia)
- Hepatic overproduction of VLDL
- Causes pancreatitis
- Increased circulating VLDL, elevated TGs
-
Abetalipoproteinemia
- Deficiency of apo B100 and apo B48
- AR
- Accumulation of lipoproteins in enterocytes
- FTT, steatorrhea, acanthocytosis, ataxia, night blindness
|
|
