Week 2 Biochemical genetic disorders

Question 1

PKU is a disorder of what biochemical classification?

Answer 1

Amino acid disorder

Question 2

What enzyme is defective in PKU?

Answer 2

Phenylalanine hydroxylase (PAH)

Question 3

What is the mechanism of PKU?

Answer 3

Phenylalanine cannot be converted into tyrosine, phenylalanine buildup causes neurotoxicity

Question 4

What is the clinical presentation of PKU?

Answer 4

Developmental delay beginning around 3-4 months

Question 5

What tests are used to diagnose PKU? What would you expect the results to be?

Answer 5

Plasma amino acid quantitation, high phenylalanine levels

Question 6

Methylmalonic aciduria is a disorder of what biochemical classification?

Answer 6

Organic acid disorder

Question 7

What enzyme is defective in methylmalonic aciduria?

Answer 7

Methylmalonyl-CoA mutase

Question 8

What is the mechanism of methylmalonic aciduria?

Answer 8

Methylmalonyl-CoA cannot be converted into succinyl-CoA, methylmalonyl-CoA buildup causes severe acidosis

Question 9

What is the treatment for PKU?

Answer 9

Low protein diet

Question 10

What is the clinical presentation of methylmalonic aciduria?

Answer 10

Severe acidosis in the first week of life

Question 11

What tests are used to diagnose methylmalonic aciduria? What would you expect the results to be?

Answer 11

Urine organic acid quantitation, high methylmalonic acid

Question 12

What is the treatment for methylmalonic aciduria?

Answer 12

Low protein diet, some patients respond to vitamin B12 injections (cofactor for affected enzyme)

Question 13

Ornithine transcarbamylase deficiency (OTC) is a disorder of what biochemical classification?

Answer 13

Urea cycle defect

Question 14

What enzyme is defective in OTC deficiency?

Answer 14

Ornithine transcarbamylase synthetase

Question 15

What is the mechanism of OTC deficiency?

Answer 15

Bidirectional conversion between ornithine and citrulline is blocked (urea cycle), leads to ammonia buildup

Question 16

What is the clinical presentation of OTC deficiency?

Answer 16

Severe hyperammonemia in neonate, can cause neurological damage if not treated quickly

Question 17

What tests are used to diagnose OTC deficiency? What would you expect the results to be?

Answer 17

Urine amino acid quantitation, low citrulline

Question 18

What is the treatment for OTC deficiency?

Answer 18

Low protein diet, ammonia scavengers

Question 19

Hereditary fructose intolerance (HFI) is a disorder of what biochemical classification?

Answer 19

Carbohydrate disorder

Question 20

What enzyme is defective in HFI?

Answer 20

Aldolase B (fructose-1-phosphate aldolase)

Question 21

What is the mechanism of HFI?

Answer 21

Fructose cannot be metabolized to glucose, leades to fructose-1-phosphate buildup in the liver, kidneys, and small intestine

Question 22

What is the clinical presentation of HFI?

Answer 22

Vomiting and hypoglycemia after fructose ingestion, chronic hepatomegaly and renal dysfunction

Question 23

What tests are used to diagnose HFI?

Answer 23

Clinical suspicion, molecular analysis of aldolase B

Question 24

What is the treatment for HFI?

Answer 24

Restrict fructose intake (fruit, vegetables, corn syrup, table sugar)

Question 25

Lesch-Nyhan disease is a disorder of what biochemical classification?

Answer 25

Purine reclamation disorder

Question 26

What enzyme is defective in Lesch-Nyhan disease?

Answer 26

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)

Question 27

What is the mechanism of Lesch-Nyhan disease?

Answer 27

Defective purine reclamation leads to buildup of guanine and hypoxanthine causes buildup of uric acid

Question 28

What is the clinical presentation of Lesch-Nyhan disease?

Answer 28

Severe neurological dysfunction, self mutilating behavior, intellectual disability

Question 29

What tests are used to diagnose Lesch-Nyhan disease? What would you expect to see?

Answer 29

Clinical suspicion, high uric acid on urine organic acid quantitation, molecular analysis of HGPRT

Question 30

What is the treatment for Lesch-Nyhan disease?

Answer 30

Low purine diet, symptom management of neurological manifestations

Question 31

Medium chain acyl-CoA dehydrogenase deficiency (MCAD) is a disorder of what biochemical classification?

Answer 31

Fatty acid oxidation disorder

Question 32

What enzyme is defective in MCAD?

Answer 32

Medium chain acyl-CoA dehydrogenase

Question 33

What is the mechanism of MCAD?

Answer 33

Defective fatty acid oxidation leads to buildup of metabolic intermediates

Question 34

What is the clinical presentation of MCAD?

Answer 34

Lethargy and vomiting after fasting, hypoketoic hypoglycemia

Question 35

What tests are used to diagnose MCAD? What would you expect the results to be?

Answer 35

Elevated fatty acid oxidation intermediates on urine organic acid quantitation, acylcarnitine analysis

Question 36

What is the treatment for MCAD?

Answer 36

Avoidance of fasting, rapid treatment of hypoglycemia

Question 37

Biotinidase deficiency is a disorder of what biochemical classification?

Answer 37

Vitamin reclamation disorder

Question 38

What enzyme is defective in biotinidase deficiency?

Answer 38

Biotinidase

Question 39

What is the mechanism of biotinidase deficiency?

Answer 39

Defective reclamation of biotin leads to biotin deficiency

Question 40

What is the clinical presentation of biotinidase deficiency?

Answer 40

Alopecia, dermatitis, deafness, seizures, neurologic deterioration starting at 4-6 months

Question 41

What tests are used to diagnose biotinidase deficiency'

Answer 41

Enzyme assay

Question 42

What is the treatment for biotinidase deficiency?

Answer 42

Biotin supplementation

Question 43

Tay-Sachs disease is a disorder of what biochemical classification?

Answer 43

Lysosomal storage disorder

Question 44

What enzyme is deficient in Tay-Sachs disease?

Answer 44

beta-hexoaminidase A

Question 45

What is the mechanism for Tay-Sachs disease?

Answer 45

Defective beta-hexoaminidase A leads to lipid accumulation in the brain

Question 46

What is the clinical presentation of Tay-Sachs disease?

Answer 46

Neurological degeneration, hypotonia, spasticity, seizures, blindness, death at 2-4 years

Question 47

What is the treatment for Tay-Sachs disease?

Answer 47

None; symptom management

Question 48

Hunter syndrome is a disorder of what biochemical classification?

Answer 48

Lysosomal storage disorder

Question 49

What enzyme is defective in Hunter syndrome?

Answer 49

Iduronate-2-sulfatase

Question 50

What is the mechanism of Hunter syndrome?

Answer 50

Defective iduronate-2-sulfatase leads to accumulation of mucopolysaccharides (especially heparin sulfate and dermatan sulfate)

Question 51

What is the clinical presentation of Hunter syndrome?

Answer 51

Craniofacial anomalities, neurological degeneration

Question 52

What tests are used to diagnose Hunter syndrome?

Answer 52

Enzyme assay

Question 53

What is the treatment for Hunter syndrome?

Answer 53

Enzyme replacement therapy