Cobalamin and Inborn Errors of Cobalamin Absorption and Metabolism

Cobalamin (Cbl), or vitamin B12, is required for activity of the mitochondrial enzyme, methylmalonyl-CoA mutase, and the cytoplasmic enzyme, methionine synthase. A number of inborn errors affecting ability to absorb dietary cobalamin or to convert exogenous cobalamin to its active coenzyme derivatives have been recognized. Intrinsic factor deficiency and Imerslund-Gräsbeck syndrome result in inability to absorb dietary cobalamin from the gut. Transcobalamin II deficiency results in decreased levels of the blood cobalamin-binding protein that facilitates cellular cobalamin uptake. The inborn errors of cobalamin metabolism, the CblA– CblH disorders, result in inability to synthesize one or both of the cobalamin coenzyme derivatives, adenosylcobalamin and methylcobalamin, resulting in methylmalonic aciduria or hyperhomocystinemia and hypomethioninemia, or both.