A 9-month-old breastfed infant from a strictly vegetarian family presents with hypotonia, developmental regression (loss of previously achieved milestones), megaloblastic anemia, and elevated homocysteine. Serum B12 is <100 pg/mL. What is the MECHANISM of neurological damage in vitamin B12 deficiency?

• A Deficiency of DNA synthesis causing neuronal apoptosis directly
• B Elevated homocysteine causing direct excitotoxic neuronal injury
• C Iron deficiency co-occurring with B12 deficiency causing white matter changes
• D Impaired myelin synthesis due to failure of methylmalonyl-CoA conversion to succinyl-CoA (disruption of odd-chain fatty acid metabolism in myelin) ✓

Explanation

Vitamin B12 is a cofactor for two enzymes: methionine synthase (converts homocysteine to methionine — for methylation reactions/myelin basic protein) and methylmalonyl-CoA mutase (converts methylmalonyl-CoA to succinyl-CoA — for odd-chain fatty acid entry into TCA cycle). B12 deficiency impairs the latter reaction, causing methylmalonyl-CoA accumulation, which disrupts myelin fatty acid synthesis (odd-chain fatty acids incorporated into myelin membranes instead of normal fatty acids), leading to demyelination — subacute combined degeneration of spinal cord and peripheral neuropathy. This explains neurological regression without structural brain abnormality. Developmental regression in an exclusively breastfed infant of vegetarian mother is a classic high-yield scenario.

Reference: Ghai Essential Pediatrics, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.