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Nonradioactive Vitamin B₁₂ Absorption Test Evaluated in Controls and in Patients with Inherited Malabsorption of Vitamin B₁₂

Mustafa Vakur Bor^1,2,a, Mualla Çetin³, Selin Aytaç³, Çidem Altay³ and Ebba Nexo¹

¹ Department of Clinical Biochemistry, NBG, AS, and² Department of Clinical Biochemistry, Aalborg Hospital, Aarhus University Hospital, Aarhus, Denmark.
³ Department of Pediatrics, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

^aAddress correspondence to this author at: Department of Clinical Biochemistry, NBG, AS, Aarhus University Hospital, Norrebrogade 44, DK-8000 Aarhus C, Denmark. Fax 45-89493060; e-mail vakurbor{at}hotmail.com.

Background: Current tests for evaluation of vitamin B₁₂ absorption are problematic because they involve the use of radioactively labeled vitamin B₁₂. We describe a vitamin B₁₂ absorption test that circumvents this problem.

Methods: We measured cobalamin or transcobalamin saturated with cobalamin (holo-TC) 24 h after three 9-µg doses of vitamin B₁₂ given orally at 6-h intervals. We studied 17 patients with inherited malabsorption of vitamin B₁₂ attributable to Imerslund–Grasbeck syndrome (n = 13) or intrinsic factor deficiency (n = 4), their obligate heterozygous biological parents (n = 19), and healthy controls (n = 44).

Results: In the patients, the median (range) change of holo-TC after the B₁₂ load was not significant [1 (–42 to 5) pmol/L], nor was the change of cobalamin [–3 (–32 to 22) pmol/L], consistent with a lack of measurable active or passive absorption. In controls, however, the median (range) increases of holo-TC and cobalamin were 26 (–6 to 63) pmol/L and 41 (–37 to 109) pmol/L, respectively. Similarly, the parents showed increases of 23 (–2 to 47) pmol/L and 27 (–15 to 94) pmol/L. The mean areas under the ROC curves (95% confidence intervals) were 0.97 (0.93–1.0) for holo-TC and 0.87 (0.79–0.94) for cobalamin, distinguishing patients from controls. At a cutoff of 6 pmol/L for holo-TC, the diagnostic sensitivity (95% confidence interval) was 100 (81–100)%, and the diagnostic specificity was 92 (82–97)%.

Conclusion: Measurement of holo-TC after administration of vitamin B₁₂ is a promising approach for evaluating vitamin B₁₂ absorption.

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