Clinical utility of serum holotranscobalamin as a marker of cobalamin status in elderly patients with neuropsychiatric symptoms

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Early diagnosis of cobalamin deficiency is crucial, owing to the latent nature of this disorder and the resulting possible irreversible neurological damage. A normal serum cobalamin concentration does not reliably rule out a functional cobalamin deficiency and there does not at present seem to be any single diagnostic approach to achieve this diagnosis. A new marker for cobalamin status is the serum concentration of cobalamin bound to transcobalamin II (holoTC). Because methods suitable for routine use have been unavailable until recently, the clinical value of low holoTC is still uncertain. Furthermore, there is at the moment no gold standard or true reference method to diagnose subtle cobalamin deficiency, which makes evaluation of the clinical usefulness of holoTC and the estimation of sensitivity and specificity problematic. In this study, we aimed to assess whether low holoTC concentrations are congruent with other biochemical signs of cobalamin deficiency in a group of psychogeriatric patients. The findings in the present study show that holoTC is strongly related to serum cobalamin (0.68; p<0.001 in both patients and controls). Distribution of the different markers for cobalamin/folate status in the 33 patients with low levels of serum holoTC (below 40 pmol/l) showed that 17 patients had normal levels of the other markers for cobalamin status. This may indicate poor specificity of low holoTC for cobalamin deficiency. In 23 out of 176 patients with normal levels of holoTC we observed pathological levels of other markers for cobalamin deficiency. The use of holoTC in the present study group did not give significant additional information other than that given by serum cobalamin and therefore cannot be recommended in this clinical setting.

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