Transcobalamin II deficiency with methylmalonic aciduria in three sisters

Transcobalamin II (TC II) is a plasma protein that binds vitamin B-12 (coba lamin, Cbl) and facilitates cellular Cbl uptake by receptor-mediated endocy tosis. In autosomal recessive TC II deficiency, intracellular Cbl deficienc y results in an early onset of megaloblastic anaemia that may be accompanie d by neurological abnormalities. Inadequate treatment may lead to neurologi cal abnormalities. We describe three sisters, the daughters of first cousin s of Moroccan origin, with TC II deficiency requiring continuous and long-t erm 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 fibroblas ts to synthesize TC II.