Week 2 Biochemical genetic disorders Flashcards
PKU is a disorder of what biochemical classification?
Amino acid disorder
What enzyme is defective in PKU?
Phenylalanine hydroxylase (PAH)
What is the mechanism of PKU?
Phenylalanine cannot be converted into tyrosine, phenylalanine buildup causes neurotoxicity
What is the clinical presentation of PKU?
Developmental delay beginning around 3-4 months
What tests are used to diagnose PKU? What would you expect the results to be?
Plasma amino acid quantitation, high phenylalanine levels
Methylmalonic aciduria is a disorder of what biochemical classification?
Organic acid disorder
What enzyme is defective in methylmalonic aciduria?
Methylmalonyl-CoA mutase
What is the mechanism of methylmalonic aciduria?
Methylmalonyl-CoA cannot be converted into succinyl-CoA, methylmalonyl-CoA buildup causes severe acidosis
What is the treatment for PKU?
Low protein diet
What is the clinical presentation of methylmalonic aciduria?
Severe acidosis in the first week of life
What tests are used to diagnose methylmalonic aciduria? What would you expect the results to be?
Urine organic acid quantitation, high methylmalonic acid
What is the treatment for methylmalonic aciduria?
Low protein diet, some patients respond to vitamin B12 injections (cofactor for affected enzyme)
Ornithine transcarbamylase deficiency (OTC) is a disorder of what biochemical classification?
Urea cycle defect
What enzyme is defective in OTC deficiency?
Ornithine transcarbamylase synthetase
What is the mechanism of OTC deficiency?
Bidirectional conversion between ornithine and citrulline is blocked (urea cycle), leads to ammonia buildup
What is the clinical presentation of OTC deficiency?
Severe hyperammonemia in neonate, can cause neurological damage if not treated quickly
What tests are used to diagnose OTC deficiency? What would you expect the results to be?
Urine amino acid quantitation, low citrulline
What is the treatment for OTC deficiency?
Low protein diet, ammonia scavengers
Hereditary fructose intolerance (HFI) is a disorder of what biochemical classification?
Carbohydrate disorder
What enzyme is defective in HFI?
Aldolase B (fructose-1-phosphate aldolase)
What is the mechanism of HFI?
Fructose cannot be metabolized to glucose, leades to fructose-1-phosphate buildup in the liver, kidneys, and small intestine
What is the clinical presentation of HFI?
Vomiting and hypoglycemia after fructose ingestion, chronic hepatomegaly and renal dysfunction
What tests are used to diagnose HFI?
Clinical suspicion, molecular analysis of aldolase B
What is the treatment for HFI?
Restrict fructose intake (fruit, vegetables, corn syrup, table sugar)
Lesch-Nyhan disease is a disorder of what biochemical classification?
Purine reclamation disorder
What enzyme is defective in Lesch-Nyhan disease?
Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
What is the mechanism of Lesch-Nyhan disease?
Defective purine reclamation leads to buildup of guanine and hypoxanthine causes buildup of uric acid
What is the clinical presentation of Lesch-Nyhan disease?
Severe neurological dysfunction, self mutilating behavior, intellectual disability
What tests are used to diagnose Lesch-Nyhan disease? What would you expect to see?
Clinical suspicion, high uric acid on urine organic acid quantitation, molecular analysis of HGPRT
What is the treatment for Lesch-Nyhan disease?
Low purine diet, symptom management of neurological manifestations
Medium chain acyl-CoA dehydrogenase deficiency (MCAD) is a disorder of what biochemical classification?
Fatty acid oxidation disorder
What enzyme is defective in MCAD?
Medium chain acyl-CoA dehydrogenase
What is the mechanism of MCAD?
Defective fatty acid oxidation leads to buildup of metabolic intermediates
What is the clinical presentation of MCAD?
Lethargy and vomiting after fasting, hypoketoic hypoglycemia
What tests are used to diagnose MCAD? What would you expect the results to be?
Elevated fatty acid oxidation intermediates on urine organic acid quantitation, acylcarnitine analysis
What is the treatment for MCAD?
Avoidance of fasting, rapid treatment of hypoglycemia
Biotinidase deficiency is a disorder of what biochemical classification?
Vitamin reclamation disorder
What enzyme is defective in biotinidase deficiency?
Biotinidase
What is the mechanism of biotinidase deficiency?
Defective reclamation of biotin leads to biotin deficiency
What is the clinical presentation of biotinidase deficiency?
Alopecia, dermatitis, deafness, seizures, neurologic deterioration starting at 4-6 months
What tests are used to diagnose biotinidase deficiency’
Enzyme assay
What is the treatment for biotinidase deficiency?
Biotin supplementation
Tay-Sachs disease is a disorder of what biochemical classification?
Lysosomal storage disorder
What enzyme is deficient in Tay-Sachs disease?
beta-hexoaminidase A
What is the mechanism for Tay-Sachs disease?
Defective beta-hexoaminidase A leads to lipid accumulation in the brain
What is the clinical presentation of Tay-Sachs disease?
Neurological degeneration, hypotonia, spasticity, seizures, blindness, death at 2-4 years
What is the treatment for Tay-Sachs disease?
None; symptom management
Hunter syndrome is a disorder of what biochemical classification?
Lysosomal storage disorder
What enzyme is defective in Hunter syndrome?
Iduronate-2-sulfatase
What is the mechanism of Hunter syndrome?
Defective iduronate-2-sulfatase leads to accumulation of mucopolysaccharides (especially heparin sulfate and dermatan sulfate)
What is the clinical presentation of Hunter syndrome?
Craniofacial anomalities, neurological degeneration
What tests are used to diagnose Hunter syndrome?
Enzyme assay
What is the treatment for Hunter syndrome?
Enzyme replacement therapy
