A 9-month-old exclusively breastfed infant from a vegetarian family presents with developmental regression, hypotonia, and macrocytic anemia. Serum B12 is 80 pg/mL (normal > 200). Which of the following correctly identifies the mechanism of neurological damage in vitamin B12 deficiency?
- A Defective thymidylate synthesis causing DNA strand breaks in neurons
- B Inhibition of cytochrome c oxidase causing mitochondrial failure
- C Increased homocysteine causing oxidative neuronal injury only
- D Impaired myelin synthesis due to defective methylmalonyl-CoA mutase reaction affecting odd-chain fatty acid metabolism ✓
Explanation
Neurological damage in B12 deficiency results from defective methylmalonyl-CoA mutase activity (which requires adenosylcobalamin as cofactor), leading to accumulation of methylmalonic acid and propionyl-CoA. These odd-chain fatty acid metabolites are incorporated into myelin, producing abnormal, unstable myelin (subacute combined degeneration). This is distinct from the hematological effects (which involve methylcobalamin-dependent methionine synthase and thymidylate synthesis). Elevated homocysteine contributes to vascular and oxidative injury but is not the primary mechanism of neurological damage. Infantile B12 deficiency from breastfeeding vegetarian mothers is a well-recognized and entirely preventable cause of developmental regression.
Reference: Ghai Essential Pediatrics, 10th ed.
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Written and medically reviewed by the StethoPrep medical team.