An 18-year-old male presents with progressive muscle weakness, cardiomyopathy, and peripheral neuropathy. Organic acid analysis of urine reveals elevated propionic acid and methylmalonic acid. Branched-chain amino acids such as valine, isoleucine, and threonine produce propionyl-CoA during catabolism. The accumulation pattern suggests a defect in which enzyme?
- A Methylmalonyl-CoA mutase ✓
- B Propionyl-CoA carboxylase
- C Methylmalonyl-CoA epimerase
- D Succinyl-CoA synthetase
Correct answer: A. Methylmalonyl-CoA mutase
Explanation
Methylmalonyl-CoA mutase (requires adenosylcobalamin/vitamin B12) converts L-methylmalonyl-CoA to succinyl-CoA. Its deficiency causes methylmalonic acidemia with accumulation of both methylmalonic acid and, because propionyl-CoA carboxylase is also backed up, propionic acid. Succinyl-CoA depletion impairs heme synthesis, and toxic metabolites damage myelin, causing cardiomyopathy and neuropathy. Vitamin B12 deficiency can produce an identical biochemical picture.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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