Current concepts in cobalamin deficiency

The application of sensitive metabolic tests, such as the deoxyuridine supp ression test and measurement of homocysteine and methylmalonic acid, to cob alamin status has identified the entity of mild, preclinical cobalamin defi ciency. This state, common in the elderly, responds to cobalamin therapy. P reclinical deficiency may exist within the nervous system as well, although this requires further study. Nevertheless, it is well to remember that not all low cobalamin levels and not all abnormal metabolite results reflect c obalamin deficiency. Interpretation of metabolic results still requires cau tion, as do proposals to raise the cut-off point for low cobalamin levels t o capture some normal levels that are associated with metabolic abnormality . The recognition of mild, preclinical deficiency has opened up many import ant issues. These include identifying its causes, what should be done about it, and what the clinical impact of the hyperhomocysteinemia itself is. Al though malabsorptive disorders, especially food-cobalamin malabsorption, un derlie about half of all cases of preclinical deficiency, no cause can be f ound in the remainder of these cases; poor dietary intake appears to be unc ommon. In addition, unusual states of neurologically symptomatic cobalamin deficiency are being recognized, such as nitrous oxide exposure in patients with unrecognized deficiency and severe deficiency in children of mildly d eficient mothers. All of these have broadened and complicated the picture o f cobalamin deficiency while providing greater opportunities for prevention .