Q- A 6-month-old infant has fasting hypoglycemia, a large liver, lactic acidosis, high uric acid, and high triglycerides. Which enzyme is deficient?
A- Glucose-6-phosphatase
B- Lysosomal acid alpha-glucosidase
C- Muscle glycogen phosphorylase
D- Glycogen debranching enzyme
A- Glucose-6-phosphatase. This is von Gierke disease (type I glycogen storage disease). The liver cannot release free glucose from glycogen or gluconeogenesis, so infants have severe fasting hypoglycemia, hepatomegaly, lactic acidosis, hyperuricemia, and hyperlipidemia. Acid alpha-glucosidase deficiency is Pompe disease (cardiomegaly), muscle phosphorylase deficiency is McArdle disease (exercise cramps, myoglobinuria), and debranching enzyme deficiency is Cori disease (milder, normal lactate).
Q- A 50-year-old man with chronic alcohol use presents with confusion, ophthalmoplegia, and ataxia. The deficient vitamin is a cofactor for which enzymes?
A- Pyruvate carboxylase
B- Transketolase and pyruvate dehydrogenase
C- Methylmalonyl-CoA mutase
D- Glutamate decarboxylase
B- Transketolase and pyruvate dehydrogenase. This is Wernicke encephalopathy from thiamine (vitamin B1) deficiency. Thiamine pyrophosphate is a cofactor for pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, transketolase, and branched-chain ketoacid dehydrogenase. Give thiamine before glucose. Pyruvate carboxylase needs biotin, methylmalonyl-CoA mutase needs vitamin B12, and glutamate decarboxylase needs vitamin B6.
Q- A child has intellectual disability, a musty body odor, fair skin, and eczema. A deficiency of phenylalanine hydroxylase is found. Which amino acid becomes essential in this patient?
A- Tyrosine
B- Phenylalanine
C- Tryptophan
D- Methionine
A- Tyrosine. In phenylketonuria (PKU), phenylalanine cannot be converted to tyrosine, so tyrosine must come from the diet. Phenylalanine and its metabolites (phenylketones) build up, causing the musty odor and brain damage. Treatment is a low-phenylalanine diet with tyrosine supplementation. Tyrosine is also needed for melanin, which explains the fair skin.
Q- A 3-year-old boy has developmental delay, biting of his lips and fingers, and orange crystals in his diapers. Serum uric acid is high. Which enzyme is deficient?
B- HGPRT. This is Lesch-Nyhan syndrome, an X-linked recessive defect in purine salvage. Without HGPRT, purines are degraded to uric acid and de novo purine synthesis increases, causing hyperuricemia, gout, self-mutilation, and dystonia. ADA deficiency causes SCID, xanthine oxidase is the target of allopurinol, and UMP synthase deficiency causes orotic aciduria.
Q- A 30-year-old man has yellow nodules on his Achilles tendons and a very high LDL cholesterol. His father had a myocardial infarction at age 40. What is the most likely defect?
A- Lipoprotein lipase deficiency
B- LDL receptor mutation
C- Apolipoprotein E deficiency
D- Microsomal triglyceride transfer protein deficiency
B- LDL receptor mutation. Familial hypercholesterolemia (type IIa) is autosomal dominant. Defective LDL receptors raise LDL, causing tendon xanthomas, corneal arcus, and premature coronary disease. Lipoprotein lipase deficiency (type I) raises chylomicrons and causes pancreatitis, ApoE defects cause type III dysbetalipoproteinemia, and MTP deficiency causes abetalipoproteinemia.
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