Detection of errors in methylmalonyl-CoA metabolism by using amniotic fluid.
We report a method for rapid prenatal detection of methylmalonic acidemia, consisting of measuring methylmalonly-CoA mutase (EC 5.4.99.2) activity in non-cultured amniotic cells and measuring the concentration of methylmalonate in the amniotic fluid. Immediate stabilization of the mutase activity in the non-cultured amniotic cell by its coenzyme adenosycobalamin, and use of methylmalonyl-CoA with high specific activity gives mutase activity comparable to that of cultured amniotic cells or normal fibroblasts. Consequently, findings of low mutase activity and a hight concentration of methylmalonate in the amniotic fluid allows accurate diagnosis of the vitamin B12-nonresponsive form of methylmalonic acidemia. These results can be obtained in two days. For the vitamin B12-responsive form, the correct diagnosis depends upon finding amniotic fluid methylmalonate, because cells from these patients will display normal methylmalony-CoA mutase activity after adenosylcobalamin is added. Problems in interpreting data on bloody samples and the limitations of the method are discussed.
D000653:Amniotic Fluid / Q000032:analysis* / Q000201:enzymology; D002478:Cells, Cultured; D003065:Coenzyme A / Q000378:metabolism*; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D008314:Malonates / Q000378:metabolism*; D008661:Metabolism, Inborn Errors / Q000175:diagnosis*; D008722:Methods; D008764:Methylmalonic Acid / Q000032:analysis / Q000378:metabolism*; D008765:Methylmalonyl-CoA Mutase / Q000097:blood / Q000378:metabolism; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011296:Prenatal Diagnosis
D008314:Malonates; D008764:Methylmalonic Acid; D008765:Methylmalonyl-CoA Mutase; D003065:Coenzyme A