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Enzymatic dysfunction has the following consequences: [1] Methionine synthase demethylates 5-methyltetrahydrofolate, producing tetrahydrofolic acid, a cofactor in purine synthesis, and also converts homocysteine to methionine ↓ Tetrahydrofolic acid → ↓ DNA synthesis → impaired hematopoiesis Large, nucleated hematopoietic cells, including megaloblasts, are produced, which undergo apoptosis or are phagocytosed by macrophages Pancytopenia (including megaloblastic anemia) ↓ Methionine → neuropathy [2] [5] ↑ Homocysteine → endothelial damage (increases risk for cardiovascular disease) Can cause secondary folate deficiency Methylmalonyl-CoA mutase (converts methylmalonyl-CoA to succinyl CoA) Accumulation of methylmalonyl-CoA and its precursor propionyl-CoA, as well as their associated odd-chain fatty acids, which cannot be completely metabolized Propionyl CoA replaces acetyl CoA in neuronal membranes → demyelination → neurological manifestations Folate deficiency also leads to low levels of tetrahydrofolic acid, causing megaloblastic anemia