Measurement of total vitamin B12 and holotranscobalamin, singly and in combination, in screening for metabolic vitamin B12 deficiency

Background: The standard screening test for vitamin B-12 deficiency, measurement of total plasma vitamin B-12, has limitations of sensitivity and specificity. Plasma vitamin B-12 bound to transcobalamin (holoTC) is the fraction of total vitamin B-12 available for tissue uptake and therefore has been proposed as a potentially useful alternative indicator of vitamin B-12 status. Methods: We compared the diagnostic accuracy of total vitamin B-12, holoTC, and a combination of both measures to screen for metabolic vitamin B-12 deficiency in an elderly cohort (age >= 60 years). Plasma methylmalonic acid and homocysteine were used as indicators of vitamin B-12 deficiency. Results: Low total vitamin B12 (< 148 pmol/L) and low holoTC (< 35 pmol/L) were observed in 6.5% and 8.0%, and increased methylmalonic acid (< 350 nmol/L) and homocysteine (> 13 mu mol/L) were observed in 12.1% and 17.0% of the study participants. In multiple regression models, holoTC explained 5%-6% more of the observed variance in methylmalonic acid and homocysteine than did total vitamin B-12 (P <= 0.004). ROC curve analysis indicated that total vitamin B-12 and holoTC were essentially equivalent in their ability to discriminate persons with and without vitamin B-12 deficiency. Individuals with low concentrations of both total vitamin B-12 and holoTC had significantly higher concentrations of methylmalonic acid and homocysteine than did individuals with total vitamin B-12 and/or holoTC within the reference intervals (P < 0.001). Conclusions: HoloTC and total vitamin B-12 have equal diagnostic accuracy in screening for metabolic vitamin B-12 deficiency. Measurement of both holoTC and total vitamin B-12 provides a better screen for vitamin B-12 deficiency than either assay alone. (c) 2006 American Association for Clinical Chemistry