Metabolic cobalamin deficiency in patients with low to low-normal plasma cobalamins

Over a 2-year period, we examined 48 patients with P-cobalamin levels in the difficult "grey zone" at the lower reference limit detected by a competitive protein binding assay using intrinsic factor as binder. In 21 of 30 patients (70%) with low P-cobalamins we could not establish the diagnosis of metabolic cobalamin deficiency, but 1 of 18 patients (6%) with low-normal P-cobalamin values was confirmed metabolically cobalamin-deficient. Half of these 30 patients with low P-cobalamins had neuropsychiatric disorders, but only one-third of the latter patients had metabolic cobalamin deficiency. Ten of the remaining 15 patients (67%) were characterized as non-deficient. In patients with low-normal P-cobalamin level, we found neuropsychiatric disorders in 5 of the 18 (28%), but none of these had metabolic cobalamin deficiency. We conclude that P-cobalamins below the reference interval combined with typical neuropsychiatric symptoms or findings are not diagnostic of cobalamin deficiency and that further analyses are necessary.