Measurement of Total Vitamin B12 and Holotranscobalamin, Singly and in Combination, in Screening for Metabolic Vitamin B12 Deficiency

Abstract

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 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

Holotranscobalamin and methylmalonic acid as prognostic markers following an acute myocardial infarction

“…Our population represents an age group somewhere in between with a median age of 65 (range 28-87). In an elderly cohort with a median age of 70, Miller et al (2006) found 12.1% of the population to have MMA40.35 mmol/l, a slightly higher cutoff level than the definition used in our study. In other words, our study participants seems to be representative for their age group, and irrespective of definition, most of them would actually be classified as replete.…”

“…In the older age groups, holoTC should only be considered a sensitive marker of deficiency when study participants with a creatinine4120 mmol/l are excluded from the analyses (Hvas and Nexo, 2005). In a recent study by Miller et al (2006), holoTC and total vitamin B 12 actually had equal diagnostic accuracy, even after adjustments for creatinine. As stated by Herrmann et al (2003), the accepted cutoff level for holoTC of 35 pmol/l might not be applicable in patients with renal dysfunction.…”

Determination of serum holotranscobalamin concentrations with the AxSYM active B12 assay: cut-off point evaluation in the clinical laboratory

“…There is concern about subtle cobalamin deficiency, especially in populations at risk. As reported by Miller et al (23) in a study of an elderly cohort, and confirmed by Gonzalez-Gross et al (24), measurement of both HoloTC and tB 12 concentrations provide better screening for cobalamin deficiency than either assay alone.…”

Prevalence of vitamin B12 depletion and deficiency in Liechtenstein

“…The cut-off point for B 12 depletion was defined as a serum level of 125-300 pmol/l for total B 12 and a serum level of ,35 pg/l for HoloTC (9) .…”

“…To date, an internationally valid consensus as to the definition of B 12 deficiency has not been established, since different thresholds have been used (9) . The transition from B 12 depletion to deficiency is fluid.…”