Mild Transcobalamin I (Haptocorrin) Deficiency and Low Serum Cobalamin Concentrations (Hematology) (Clinical Report‪)‬

Serum cobalamin concentrations are frequently below the reference interval in patients who have no obvious causes for such low concentrations, and it is often not clear what should be done about them (1, 2). Only one-half or fewer of low cobalamin concentrations are explained by malabsorption of either free or food-bound cobalamin, and dietary insufficiency is uncommon even among the elderly (2-6). Moreover, metabolic studies indicate that 15-40% of patients with low serum cobalamin do not have cobalamin deficiency (1, 2, 7-10), which suggests that as many as 15-40% of cobalamin values below the reference interval may be diagnostically misleading. This diagnostic dilemma is not resolved by changing reference intervals for cobalamin because low concentrations that represent true metabolic deficiency and malabsorption are not always lower than low concentrations that do not. Among the few known nonmalabsorptive causes of low cobalamin concentrations is hereditary absence of transcobalamin I/haptocorrin (TC I/HC) [1,2] (11-16), which causes low serum cobalamin concentrations because most cobalamin circulates in the blood attached to TC I/HC (17-19). Neither malabsorption nor cellular deficiency of cobalamin results from the absence of TC I/HC, which unlike transcobalamin II is not needed for cellular uptake of cobalamin.