Background: Decreased serum holo-transcobalamin (holoTC) could be the earliest marker of cobalamin (Cbl) deficiency, but there has been no method suitable for routine use. We evaluated a new commercial holoTC RIA, determined reference values, and assessed holoTC concentrations in relation to other biochemical markers of Cbl deficiency.
Methods: The reference population consisted of 303 individuals 22-88 years of age, without disease or medication affecting Cbl or homocysteine metabolism. In elderly individuals (>or=65 years), normal Cbl status was further confirmed by total homocysteine (tHcy; <19 micro mol/L) and methylmalonic acid (MMA; <0.28 micro mol/L) concentrations within established reference intervals. HoloTC in Cbl deficiency was studied in a population of 107 elderly individuals with normal renal function. The Cbl deficiency was graded as potential (total Cbl <or=150 pmol/L or tHcy >or=19 micro mol/L), possible (total Cbl <or=150 pmol/L and either tHcy >or=19 micro mol/L or MMA >or=0.45 micro mol/L), and probable (tHcy >or=19 micro mol/L and MMA >or=0.45 micro mol/L).
Results: The intra- and between-assay imprecision (CV) for the holoTC RIA were 4-7% and 6-8%, respectively. A 95% central reference interval for serum holoTC was 37-171 pmol/L. All participants (n = 16) with probable Cbl deficiency, 86% of those with possible, and 30% of those with potential Cbl deficiency had holoTC below the reference limit (<37 pmol/L). The holoTC correlated with total Cbl (r(s) = 0.80; P <0.0001) and inversely with MMA (r(s) = -0.52; P <0.0001). HoloTC concentrations were significantly (P = 0.01) higher in women than in men.
Conclusions: The new holoTC RIA is precise and simple to perform. Low holoTC is found in individuals with biochemical signs of Cbl deficiency, but the sensitivity and specificity of low holoTC in diagnosis of Cbl deficiency need to be further evaluated.