17. Inborn Errors of Metabolism

Question 1

Enzyme deficient in classical galactosemia.

Answer 1

Galactose-1-Phosphate Uridyl Transferase

Question 2

Major symptoms of classical galactosemia due to formation of galactitol and galactonate.

Answer 2

Cataracts

Question 3

Enzyme deficient in hereditary fructose intolerance.

Answer 3

Fructose-1,6-bisphosphate Aldolase

Question 4

Enzyme deficient in Von Gierke Disease and common symptoms.

Answer 4

1. Glucose-6-phosphatase
2. Patients cannot release glucose from glycogen storage which leads to hepatomegaly, enlarged and painful skeletal muscles, and overall hypoglycemia.

Question 5

Enzyme deficient in Phenylketonuria and common symptoms.

Answer 5

1. Phenylalanine Hydroxylase (PAH)

2. Patients develop mental retardation because of an inability to make Tyrosine.

Question 6

Maple syrup urine disease results from what deficiency.

Answer 6

Lack of enzymes required to metabolize branched chain amino acids (BCAA).

Question 7

Describe MCAD deficiency.

Answer 7

1. Defect in the enzyme Medium-chain acyl-coenzyme A dehydrogenase (MCAD).
2. Pts. cannot metabolise medium chain fatty acids. Must eat constantly to keep glycogen stores up preventing fatty acid metabolism.

Question 8

What defects occur in congenital adrenal hyperplasia?

Answer 8

A block in corticosteroid synthesis occurs, so precursors of this pathway move down the androgen pathway. Virilization (de-feminizing or musculinization) of females often occurs.

Question 9

Most common enzyme deficiency in congenital adrenal hyperplasia.

Answer 9

21-hydroxylase

Question 10

Mutation in peroxisome formation.

Answer 10

Zellwegger Syndrome

Question 11

Mucopolysaccharidosis (lysosomal storage) disorders are all autosomal recessive except for 1.

Answer 11

Hunter Syndrome (X-linked)

Question 12

Mucopolysaccharidosis that results in an inability to remodel long bones correctly and the skull becomes deformed with age.

Answer 12

Hurler Syndrome

Question 13

Mucolipidosis (lysosomal storage) disorder with a Beta-glucosidase deficiency.

Answer 13

Gaucher’s Disease

Question 14

Mucolipidosis (lysosomal storage) disorder with a Beta-hexosaminidase A deficiency.

Answer 14

Tay Sachs Disease

Question 15

Mucolipidosis (lysosomal storage) disorder with a Sphingomyelinase deficiency.

Answer 15

Niemann Pick Disease

Question 16

Defect in mannose-6-phosphate preventing enzymes to target lysosomes.

Answer 16

I-cell disease (lysosomal enzymes don’t reach the lysosomes)

Question 17

Most common urea cycle disorder resulting in high levels of ammonia in the blood.

Answer 17

Ornithine transcarbamoylase (OTC) deficiency

Question 18

Name the protein transporters that are defective in cystinurias type 1 and type 2,3.

Answer 18

1. SLC3A1
2. SLC7A9
   (SLC - soluble ligand carrier)

Question 19

What is a major symptom of cystinurias.

Answer 19

Formation of kidney stones (calculi). Inability to remove dibasic AA from nephron tubule. Usually cystine (two cysteines joined by a disulfide bond)

Question 20

Defect in copper excretion. Results in liver disease, kidney damage, and Kayser-Fleischer ring in the eye.

Answer 20

Wilson’s Disease

Mutation in ATP7B gene

Question 21

Disease with excess iron in liver, kidney, heart and joints. Results in liver cirhossis, joint pain, and hemosiderin stain in liver biopsy.

Answer 21

Hereditary Hemochromatosis

Question 22

Defective gene in Hereditary Hemochromatosis that leads to excess iron uptake by the liver and small intestine epithelium.

Answer 22

HFE - this gene normally inhibits transferrin so that iron cannot be taken up into cells