Background: Vitamin B12 deficiency occurs frequently, especially among the elderly. However, screening for vitamin B12 deficiency is hampered by poor sensitivity of the existing total vitamin B12 assay. Methylmalonic acid (MMA) is considered as the most representative indicator of metabolic vitamin B12 deficiency and is used as such in this study. The aim of this study was to validate the clinical usefulness of holotranscobalamin (holoTC) as an initial screening assay for metabolic vitamin B12 deficiency in a mixed patient population.

Methods: Three hundred and sixty blood samples were collected by five Dutch hospitals. Vitamin B12 and holoTC in serum were measured (AxSYM; Abbott). MMA in serum was measured by tandem mass spectrometry (LC-MS/MS).

Results: Receiver operating curve (ROC) analysis demonstrated a greater area under the curve (AUC) for holoTC than for vitamin B12 in detecting vitamin B12 deficiency characterized by three predefined cut-off levels of MMA. A cut-off value of 32 pmol/L of holoTC resulted in the highest sensitivity (83%) with acceptable specificity (60%) in detecting MMA concentrations above 0.45 mmol/L. The combination of vitamin B12 and holoTC did not improve diagnostic accuracy at this cut-off level.

Conclusions: HoloTC has a better diagnostic accuracy than vitamin B12 and can replace the existing vitamin B12 assay as a primary screening test in patients suspected of vitamin B12 deficiency. Critical evaluation of cut-off values of holoTC indicated that a cut-off value of 32 pmol/L can be considered in screening for metabolic vitamin B12 deficiency (defined by MMA . 0.45mmol/L) in a mixed patient population.

dx.doi.org/10.1258/acb.2011.011039, hdl.handle.net/1765/64748
Annals of Clinical Biochemistry
Erasmus MC: University Medical Center Rotterdam

Heil, S.G, de Jonge, R, de Rotte, M.C.F.J, van Wijnen, M, Heiner-Fokkema, R.M.R, Kobold, A.C.M, … Lindemans, J. (2012). Screening for metabolic vitamin B12 deficiency by holotranscobalamin in patients suspected of vitamin B12 deficiency: A multicentre study. Annals of Clinical Biochemistry, 49(2), 184–189. doi:10.1258/acb.2011.011039