Submitted to: Clinical Chemistry
Publication Type: Review article
Publication Acceptance Date: 12/29/2005
Publication Date: 2/1/2006
Citation: Miller, J.W., Garrod, M.G., Rockwood, A.L., Kushnir, M.M., Allen, L.H., Haan, M.N., Green, R. Measurement of total vitamin b12 and holotranscobalamin, singly and in cobmination, in screening for metabolic vitamin b12 deficiency. Clinical Chemistry. 52 (2): 278-85, 2006. Interpretive Summary: Vitamin B12 status is usually assessed by measuring the concentration of total vitamin B12 in plasma, but it has been suggested that measuring only fraction of total plasma B12 is bound to transcobalamin in plasma would improve the sensitivity and specificity of detecting vitamin B12 deficiency. We tested this suggestion by comparing the ability of measures to detect metabolic B12 deficiency, detected as elevated plasma mthylmalonic acid or homocysteine, in a large cohort aged >60 years. Plasma total vitamin B12 or holotranscobalamin were equally accurate in screening metabolic vitamin B12 deficiency, but the best indicator was low total vitamin B12 plus low holotranscobalamin.
Technical Abstract: Background: The standard screening test for vitamin B12 deficiency, measurement of total plasma vitamin B12, has limitations of sensitivity and specificity. Plasma vitamin B12 bound to transcobalamin (holoTC) is the fraction of total vitamin B12 available for tissue uptake and therefore has been proposed as a potentially useful alternative indicator of vitamin B12 status. Methods: We compared the diagnostic accuracy of total vitamin B12, holoTC, and a combination of both measures to screen for metabolic vitamin B12 deficiency in an elderly cohort (age '60 years). Plasma methylmalonic acid and homocysteine were used as indicators of vitamin B12 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 umol/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 B12 (P <0.004). ROC curve analysis indicated that total vitamin B12 and holoTC were essentially equivalent in their ability to discriminate persons with and without vitamin B12 deficiency. Individuals with low concentration of both total vitamin B12 and holoTC had significantly higher concentrations of methylmalonic acid and homocysteine than individuals with total vitamin B12 and/or holoTC within the reference intervals (P <0.001). Conclusions: HoloTC and total vitamin B12 have equal diagnostic accuracy in screening for metabolic vitamin B12 deficiency. Measurement of both holoTC and total vitamin B12 provides a better screen for vitamin B12 deficiency than either assay alone.