Prenatal vitamin B12 therapy of a fetus with methylcobalamin deficiency (cobalamin E disease).

A child presented early in life with homocystinuria and megaloblastic anaemia which responded to hydroxocobalamin (OH-B12) therapy. Mental development has been subnormal since birth. Fibroblasts from this patient contained low levels of methylcobalamin (CH3-B12) and incorporated less 14C from labelled 5-methyltetrahydrofolate (14CH3H4PteGlu) into methionine. Methionine synthase activity was more thiol-dependent in the patient's fibroblasts than it was in normal cells. Studies on fibroblasts from the parents confirmed that both are heterozygous for this disorder. When the mother became pregnant again, prenatal diagnosis was attempted by use of cultured amniocytes obtained at 16 weeks' gestation. Values for incorporation of 14CH3H4PteGlu into methionine by intact cells and the thiol requirement of methionine synthase were abnormal in these amniocytes but these features did not conclusively identify the fetus at risk as being homozygous for the abnormality. Only 8% of the 57Co vitamin B12 incorporated by the fetal amniocytes was present as CH3-B12 compared with 29% and 40% in two control amniocyte lines and 37% and 32% in fibroblasts from the parents who are obligate heterozygotes. These studies suggested that the fetus had CH3-B12 deficiency. The mother was treated with OH-B12 (1 mg twice weekly, intramuscularly) from 25 weeks' gestation. The baby was clinically normal at birth without any evidence of homocystinuria or anaemia, and has been maintained on OH-B12 (1 mg twice weekly). Studies on fibroblasts from the baby confirmed the diagnosis of CH3-B12 deficiency (cobalamin E disease). At 6 months of age, growth and development remain normal.