cobalamin

Cobalamin (B12) requires intrinsic factor (secreted by gastric parietal cells) for absorption in the terminal ileum. It acts as a cofactor in two key reactions: (1) methionine synthase, which converts homocysteine to methionine (regenerating tetrahydrofolate for DNA synthesis), and (2) methylmalonyl-CoA mutase, which converts methylmalonyl-CoA to succinyl-CoA in fatty acid metabolism. Deficiency leads to elevated homocysteine and methylmalonic acid (MMA), the latter distinguishing B12 deficiency from folate deficiency (folate deficiency raises homocysteine but not MMA). Clinical manifestations include megaloblastic anemia (identical to folate deficiency on peripheral smear with hypersegmented neutrophils and macro-ovalocytes) plus neurologic findings unique to B12 deficiency: subacute combined degeneration affecting the dorsal columns (proprioception/vibration loss), corticospinal tracts (spasticity, weakness), and spinocerebellar tracts (ataxia), due to impaired myelin synthesis from methylmalonyl-CoA accumulation. Common causes include pernicious anemia (autoimmune destruction of parietal cells or anti-intrinsic factor antibodies), gastrectomy, ileal resection/Crohn's disease, strict vegan diet, and Diphyllobothrium latum (fish tapeworm) infection. Diagnosis involves low serum B12, elevated MMA and homocysteine; the Schilling test (historically used) differentiates causes of malabsorption. Treatment is intramuscular B12 injections (bypassing absorption issues) or high-dose oral supplementation. Important board pearl: never treat B12 deficiency with folate alone, as this can mask the anemia while allowing irreversible neurologic damage to progress.