Holotranscobalamin as a predictor of vitamin B-12 status

We report on the performance of a new test, holotranscobalamin, as compared to well established markers of vitamin B-12 deficiency (plasma cobalamins, methylmalonic acid, and homocysteine). Holotranscobalamin was analyzed in 143 samples by a competitive radiobinding assay (AxisShield). Employing a cutoff value of 50 pmol/l, holotranscobalamin showed a sensitivity of 1.00 and a specificity of 0.89 as regards discriminating between individuals with test results indicating vitamin B12 deficiency (methylmalonic acid >0.70 mol/l and plasma cobalamins <200 pmol/l, n = 35) and individuals with test results inside the reference intervals (methylmalonic acid <0.29 mol/l and plasma cobalamins greater than or equal to200 pmol/l, n = 35). In a group (n = 37) with low plasma cobalamins (<200 pmol/l) and normal methylmalonic acid (<0.29 mol/l), 27 individuals had low holotranscobalamin, and in nine of these individuals plasma homocysteine supported the deficiency state (homocysteine >15 mol/l). Holotranscobalamin was low in 12 individuals with increased methylmalonic acid (>0.40 mol/l) and normal plasma cobalamins (greater than or equal to200 pmol/l) (n = 36), and plasma homocysteine supported the deficiency state in four of these individuals. We conclude that holotranscobalamin is likely to be a sensitive marker of vitamin B12 deficiency that also has a reasonable specificity. Largescale clinical studies are warranted in order to clarify the usefulness of holotranscobalamin in the clinical setting.