Nonradioactive vitamin B₁₂ absorption test evaluated in controls and in patients with inherited malabsorption of vitamin B₁₂

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.