A new indicator of cobalamin deficiency

We designed a new indicator of cobalamin deficiency, a condition that sometimes can be difficult to diagnose.

The new indicator is a combination of the plasma concentrations of cobalamin (P-cobalamin) and methylmalonic acid (P-MMA) adjusted to an estimated glomerular filtration rate (eGFR) of 100 mL/min/1.73 m², called P-MMA₁₀₀. First, P-cobalamin and P-MMA₁₀₀ are transformed to a multiplum of their median in the population (MoM-values). Second, the indicator iB12 is calculated as log₁₀[MoM(P-cobalamin)]/[MoM(P-MMA₁₀₀)] and adjusted for age and sex. We studied some characteristics of iB12 with data from 83119 patients in primary health care, and compared it to the cB12 indicator calculated from P-cobalamin and P-MMA as devised by Fedosov et al. (Clin Chem Lab Med 2015; 53(8):1215-1225). The refineR software was used to classify patients as probably cobalamin sufficient and probably cobalamin insufficient, and for estimating reference limits.

Overall, the two indicators correlated closely. However, the iB12 indicator was more robust against systematic analytical changes than the cB12 indicator, and varied less with eGFR. For both indicators, a reasonably safe cut-off limit for cobalamin deficiency would be higher than their 2.5 percentile reference limit.

The new iB12 indicator is an improvement of the corresponding cB12 indicator.