cobamamide and 5-methyltetrahydrofolate

Prenatal diagnosis for combined methylmalonic aciduria and homocystinuria was performed in five at-risk pregnancies by determination of methylmalonic acid (MMA) and total homocysteine (Hcy) in amniotic fluid supernatant. The incorporation rate of [14C] propionate (+/- OHCbl) and the synthesis of cobalamin derivatives in cultured amniocytes were investigated as well as the [14C] MTHF incorporation rate in intact chorion biopsy. Our experience showed that total Hcy and MMA were clearly elevated in amniotic fluid of affected fetuses. Both the study of [14C] propionate incorporation and that of cobalamin synthesis in cultured amniocytes are useful to confirm the results of metabolite determination. The incorporation of [14C] MTHF in intact chorion biopsy seems not to be a reliable diagnostic method.

Topics: Amino Acid Metabolism, Inborn Errors; Amniocentesis; Amniotic Fluid; Cells, Cultured; Chorion; Chorionic Villi Sampling; Cobamides; Female; Gestational Age; Homocysteine; Homocystinuria; Humans; Male; Methylmalonic Acid; Pregnancy; Propionates; Tetrahydrofolates; Vitamin B 12

We describe an inborn error of vitamin B12 metabolism in an infant who had severe developmental delay, megaloblastic anemia, and homocystinuria. There was no evidence of methylmalonic aciduria or deficiency of folate or vitamin B12. Treatment with hydroxocobalamin, but not with cyanocobalamin and folic acid, resulted in rapid clinical and biochemical improvement. Cultured fibroblasts showed an absolute growth requirement for methionine, defective incorporation of radioactivity from [14C]5-methyltetrahydrofolate into protein, and normal incorporation of radioactivity from [14C]propionate, thus assigning the intracellular defect to methionine synthesis. The proportion of intracellular methylcobalamin in the fibroblasts was decreased, but that of 5'-deoxyadenosylcobalamin was normal. Methionine synthetase activity in cell extracts was normal, as was cobalamin incorporation into cultured cells. This defect differs from those described previously in being limited to methylcobalamin accumulation and defective use of 5-methyltetrahydrofolate by intact cells with normal activity of methylmalonyl CoA mutase.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Amino Acid Metabolism, Inborn Errors; Anemia, Macrocytic; Anemia, Megaloblastic; Cobamides; Fibroblasts; Homocystinuria; Humans; Hydroxocobalamin; Infant, Newborn; Male; Methionine; Propionates; Tetrahydrofolates; Vitamin B 12