Transcobalamin II deficiency with methylmalonic aciduria in three sisters

Transcobalamin II (TC II) is a plasma protein that binds vitamin B-12 (cobalamin, Cbl) and facilitates cellular Cbl uptake by receptor-mediated endocytosis. In autosomal recessive TC II deficiency, intracellular Cbl deficiency results in an early onset of megaloblastic anaemia that may be accompanied by neurological abnormalities. Inadequate treatment may lead to neurological abnormalities. We describe three sisters, the daughters of first cousins of Moroccan origin, with TC II deficiency requiring continuous and long-term vitamin B-12 treatment. The diagnosis was suspected from the finding of low unsaturated vitamin B-12 binding capacity and confirmed by absence of detectable TC II by radioimmunoassay and by inability of cultured fibroblasts to synthesize TC II.