Abstract

Cobalamin (vitamin B12) is an essential nutrient derived exclusively from bacterial sources. It is an essential cofactor for three known enzymatic reactions. Untreated deficiency, caused by either the autoimmune disease pernicious anemia or nutritional lack, results in a macrocytic anemia and/or subacute combined degeneration of the spinal cord and is eventually fatal. Cobalamin in serum is bound to two proteins, transcobalamin and haptocorrin. The former is responsible for the essential delivery of cobalamin to most tissues. Inadequate tissue availability of cobalamin results in increased concentration of methylmalonic acid and homocyst(e)ine due to inhibition of methylmalonyl-CoA mutase and methionine synthase, respectively. Strict vegetarians have long been known to be at risk of cobalamin deficiency, which develops insidiously over many years. It is now clear that a significant number of the elderly and HIV-positive individuals are also at increased risk of deficiency. Any individual with reduced ability to split cobalamin from food-protein may also become deficient even though intrinsic factor is present. Diagnosis of cobalamin deficiency has frequently relied on total serum cobalamin and the Schilling test. Newer approaches such as analysis of methylmalonic acid, homocyst(e)ine, holotranscobalamin, anti-intrinsic factor antibodies, and serum gastrin may provide more cost-effective testing, as well as identify those with a covert deficiency.