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  • Role of serum holotranscobalamin (holoTC) in the diagnosis of patients with low serum cobalamin. Comparison with methylmalonic acid and homocysteine.

Role of serum holotranscobalamin (holoTC) in the diagnosis of patients with low serum cobalamin. Comparison with methylmalonic acid and homocysteine.

Annals of hematology (2013-09-24)
A F Remacha, M P Sardà, C Canals, J M Queraltò, E Zapico, J Remacha, C Carrascosa
ABSTRACT

Plasma holotranscobalamin (holoTC) transports active cobalamin. Decreased levels of holoTC have been considered to be the earliest marker of cobalamin (Cbl) deficiency. In this work, holoTC was evaluated in low or borderline serum Cbl (LB12) and a concordance analysis was carried out with methylmalonic acid (MMA) and homocysteine (Hcy). Levels of Cbl, holoTC, MMA, and Hcy were investigated in a reference group in 106 patients with LB12 (≤200 pmol/l) and in 27 with folate deficiency (FOL). HoloTC levels were evaluated by an automated immunoassay (Active B12, Abbott Lab, Abbott Park, IL, USA). Lower levels of holoTC were observed in both LB12 and FOL groups (reference group vs LB12; p < 0.0001. Reference group vs FOL; p = 0.002). HoloTC levels were lower in LB12 than in FOL (p = 0.001). In LB12, concordance between Hcy and MMA was 82.1 % (chi-square test, p < 0.001; Kappa Index, 0.64, p < 0.0001). Concordance between Hcy and holoTC was 62 % (chi-square test, p = 0.006; Kappa index, 0.245, p = 0.006). Concordance between holoTC and MMA was 55.6 % (p = 0.233). Some cases with LB12 and elevated MMA did not show decreased holoTC. By contrast, MMA and Hcy were not increased in some patients with low holoTC and LB12. In conclusion, levels of holoTC were decreased in LB12 and FOL. In LB12 patients, holoTC concordance with MMA was poor. MMA/Hcy levels were not increased in a significant number of subjects with LB12 and low holoTC. This profile was found in iron deficiency. The significance of these changes remains to be clarified.

MATERIALS
Product Number
Brand
Product Description

Supelco
Cyanocobalamin, pharmaceutical secondary standard, certified reference material
Cyanocobalamin, European Pharmacopoeia (EP) Reference Standard
Supelco
Cyanocobalamin (Vitamin B12) solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®
Sigma-Aldrich
Cyanocobalamin, meets USP testing specifications
Sigma-Aldrich
Cyanocobalamin, tested according to Ph. Eur.
Sigma-Aldrich
Methylmalonic acid, 99%
Supelco
Cyanocobalamin (B12), analytical standard
Sigma-Aldrich
Vitamin B12, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for plant cell culture, ≥98%
Sigma-Aldrich
L-Homocysteine, ≥98.0% (NT)
Sigma-Aldrich
Vitamin B12, ≥98%