Measurement of total vitamin B12 and holotranscobalamin, singly and in combination, in screening for metabolic vitamin B12 deficiency.
Miller JW, Garrod MG, Rockwood AL, Kushnir MM, Allen LH, Haan MN, Green R.

Department of Pathology and Laboratory Medicine, University of California, Davis, Sacramento, CA.

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 B(12) (<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 mumol/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.

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