Expression of transcobalamin II by amniocytes.

Children with a genetic absence of transcobalamin 2 (TC2) are clinically asymptomatic at birth but develop severe megaloblastic anemia early in life. We have examined the incorporation of [57Co]-CN-B12 in the absence of any exogenous source of TC2 in control amniotic fluid derived cells and cultured diploid fibroblasts, and in fibroblasts from a patient with TC2 deficiency. Both control fibroblasts and amniocytes incorporated labelled B12 into TC2-B12, and the proportion of labelled TC2-B12 could be increased by growing cells in the presence of chloroquine which prevents intralysosomal hydrolysis of the TC2-B12 complex. In contrast, fibroblasts from the patient with TC2 deficiency incorporated almost no label as TC2-B12. These studies suggest that TC2 deficiency either due to aberrant production of TC2 or because of the production of an abnormal TC2 which does not bind B12 can be diagnosed before birth.