title: The use of homocysteine and other metabolites in the specific diagnosis of vitamin B-12 deficiency.
abstract: Vitamin B-12 (cobalamin) is a cofactor for only two enzymes, methionine synthase and L-methylmalonyl-CoA mutase. The serum vitamin B-12 concentration has been shown to have limitations in specificity and sensitivity in diagnosing vitamin B-12 deficiency and predicting response to therapy in subjects with clinical deficiency syndromes. Serum methylmalonic acid and/or total homocysteine concentrations have been shown to be elevated in almost every patient who has a clinical response to vitamin B-12. In elderly populations serum methylmalonic acid concentrations are elevated in the majority (60-66%) of subjects who have elevated total homocysteine concentrations, suggesting that vitamin B-12 deficiency (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 subjects vitamin B-12 and folate concentrations are both frequently in the low or low normal range, making differentiation of the clinical syndromes by use of serum vitamin concentrations problematic. Elevations of 2-methylcitric acid and cystathionine also result from vitamin B-12 deficiency. Serum N-methylglycine concentrations are normal in cobalamin deficiency but are increased in 40% of patients deficient in folate. In conclusion, elevations of methylmalonic acid and total homocysteine are very sensitive and specific in diagnosing vitamin B-12 deficiency and can be used to help differentiate vitamin B-12 deficiency from folate deficiency. Elevated total homocysteine concentrations that may have been attributed to folate deficiency in elderly subjects may in many instances be the result of vitamin B-12 deficiency even though serum vitamin B-12 concentrations are within normal limits.
authors.affiliation: University of Colorado Health Sciences Center, Denver, CO 80262, USA.
authors.forename: S P
authors.initials: SP
authors.lastname: Stabler
authors.forename: J
authors.initials: J
authors.lastname: Lindenbaum
authors.forename: R H
authors.initials: RH
authors.lastname: Allen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D005494:Folic Acid Deficiency / Q000097:blood; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D008764:Methylmalonic Acid / Q000097:blood*; D008875:Middle Aged; D014806:Vitamin B 12 Deficiency / Q000097:blood / Q000175:diagnosis*
chemical_list: D006710:Homocysteine; D008764:Methylmalonic Acid