A 58-year-old man with malabsorption develops numbness of the feet, impaired vibration sense, spasticity, and a hemoglobin of 7 g/dL with MCV 118 fL. Serum methylmalonic acid is elevated. The neurological findings result from dysfunction of which metabolic pathway?

• A Defective DNA synthesis from impaired thymidylate formation
• B Impaired conversion of homocysteine to methionine affecting myelin maintenance ✓
• C Accumulation of propionic acid in the basal ganglia
• D Deficiency of pyridoxine dependent neurotransmitter synthesis

Explanation

Vitamin A12 is a cofactor for methionine synthase, which converts homocysteine to methionine. Methionine is required for S adenosylmethionine dependent myelin methylation reactions, so A12 deficiency produces subacute combined degeneration of the spinal cord. The methylmalonyl CoA mutase defect explains elevated MMA but not myelin injury. Impaired thymidylate synthesis causes the megaloblastic anemia and is shared with folate deficiency, which is why folate alone can mask the hematologic picture while neurology worsens.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.