THE USE OF HOMOCYSTEINE AND OTHER METABOLITES IN THE SPECIFIC DIAGNOSIS OF VITAMIN-B-12 DEFICIENCY

Vitamin B-12 (cobalamin) is a cofactor for only two enzymes, methionin e synthase and L-methylmalonyl-CoA mutase. The serum vitamin B-12 conc entration has been shown to have limitations in specificity and sensit ivity in diagnosing vitamin B-12 deficiency and predicting response to therapy in subjects with clinical deficiency syndromes. Serum methylm alonic acid and/or total homocysteine concentrations have been shown t o be elevated in almost every patient who has a clinical response to v itamin B-12. In elderly populations serum methylmalonic acid concentra tions are elevated in the majority (60-66%) of subjects who have eleva ted total homocysteine concentrations, suggesting that vitamin B-12 de ficiency (with or without associated folate deficiency) and/or chronic renal insufficiency may be the primary cause of most of the elevated total homocysteine concentrations in elderly populations, In such subj ects vitamin B-12 and folate concentrations are both frequently in the low or low normal range, making differentiation of the clinical syndr omes by use of serum vitamin concentrations problematic. Elevations of 2-methylcitric acid and cystathionine also result from vitamin B-12 d eficiency. Serum N-methylglycine concentrations are normal in cobalami n deficiency but are increased in 40% of patients deficient in folate. In conclusion, elevations of methylmalonic acid and total homocystein e are very sensitive and specific in diagnosing vitamin B-12 deficienc y and can be used to help differentiate vitamin B-12 deficiency from f olate deficiency. Elevated total homocysteine concentrations that may have been attributed to folate deficiency in elderly subjects may in m any instances be the result of vitamin B-12 deficiency even though ser um vitamin B-12 concentrations are within normal limits.