Holotranscobalamin and Total Transcobalamin in Human Plasma: Determination, Determinants, and Reference Values in Healthy Adults

Abstract

Background:We developed microbiological assays (MBAs) to identify determinants and to establish reference values for cobalamin bound to transcobalamin [holotranscobalamin (holoTC)] and total TC in plasma. Methods: We captured holoTC with magnetic beads with TC antibodies and used a conventional MBA for cobalamin measurements. Total TC was determined as holoTC after TC was saturated with cyanocobalamin. The new assays were compared with published methods. Determinants and reference values were determined in 500 blood donors, ages 18 -69 years. Results: Determination of cobalamin, holoTC, and TC by MBA required <150 L. HoloTC and TC by MBA correlated with holoTC by RIA (r ‫؍‬ 0.95) and TC by ELISA (r ‫؍‬ 0.79), respectively. Between-day CVs for holoTC and total TC were 4%-9%. Women had lower holoTC than men, but only at age <45 years. In multivariate regression analyses, holoTC was positively associated with age (in women only), creatinine (in men only), and plasma concentrations of total TC, folate, and cysteine, but inversely correlated with homocysteine and methylmalonic acid. For all study participants, total TC was associated with holoTC and number of TCN2 766C alleles; in female participants only, total TC was also associated with age, homocysteine, and cysteine. Reference values were 670 -1270 pmol/L for TC and

Prevalence of vitamin B12 depletion and deficiency in Liechtenstein

“…Vitamin B 12 (B 12 , cobalamin) is a water-soluble vitamin and an essential nutrient that normally must be obtained from the diet. Metabolically, it is essential for two reactions catalysed by the enzymes methionine synthase and L-methyl-malonyl-coenzyme A mutase.…”

“…Metabolically, it is essential for two reactions catalysed by the enzymes methionine synthase and L-methyl-malonyl-coenzyme A mutase. The daily recommended daily intake of B 12 for adults is 2 mg (1) . In healthy individuals, nutritional B 12 deficiency is unusual because total body stores in adults are about 2500 mg and daily turnover is slow (2) , meaning that reserves generally remain for up to 10 years (3) .…”

“…Mild B 12 deficiency normally does not provoke clinical symptoms, but can be diagnosed by measurement of blood markers. The clinical laboratory parameters available to diagnose B 12 deficiency are serum total B 12 , transcobalamin-bound B 12 (holotranscobalamin, HoloTC: active fraction of B 12 ), plasma homocysteine (Hcy) and methylmalonic acid (MMA) (6) . The metabolites Hcy and MMA can be used as indicators of B 12 deficiency, but many factors other than y Contributed equally to this manuscript.…”

“…Furthermore, measuring MMA is complicated and expensive, requiring HPLC or GC-MS (7) . Thus algorithms for laboratory diagnosis of a B 12 -deficient status recommend the initial measurement of B 12 and HoloTC. Clarke et al state that HoloTC has better diagnostic accuracy than B 12 (77 % v. 73 %) and that the diagnostic utility is superior in the overall population as well as in patients with renal impairment (8) .…”

“…The aim of the present study was to investigate the prevalence of B 12 depletion and deficiency based on serum total B 12 and HoloTC concentrations in a representative population of Liechtenstein. Our secondary aim was to determine factors associated with depletion and deficiency.…”