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

Abstract

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.

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

“…The 40 pmol/L cut-off value we selected was also reported by other authors (18)(19)(20). We also verified the predictive ability of HoloTC at this threshold for selected tB 12 cut-off points.…”

A review of the cut-off points for the diagnosis of vitamin B12 deficiency in the general population

“…Rajan et al suggested 221 pmol/L was a more appropriate cut-off [20]. Others recommend to restructure the normal range and to raise the vitamin B 12 cut-off point for elderly to a much higher value than 220-260 pmol/L [21]. However, recently, Valente et al used the lower limit of the 95% central reference interval (123 pmol/L) as established from their reference population [22].…”

Megaloblastic Anemia and Other Causes of Macrocytosis

“…However, routine ordering of this test as part of the work-up to establish the diagnosis of vitamin B12 deficiency is not currently recommended. 43 There is currently no gold standard for diagnosing vitamin B12 deficiency. Until one is identified, it is recommended that when initial vitamin B12 values are low (i.e., <150 ng/L) and a vitamin B12 deficiency is suspected, the vitamin B12 level should be repeated on a separate occasion or tests should be used in combination (e.g., serum vitamin B12 level, MMA and homocysteine).…”