Rapid prenatal and postnatal detection of inborn errors of propionate,methylmalonate, and cobalamin metabolism: A sensitive assay using cultured cells

Summary A sensitive, reliable, and easily performed procedure is described for the prenatal and postnatal detection of inborn errors of propionate, methylmalonate, and cobalamin metabolism using cultured amniotic cells and skin fibroblasts. With this assay, control fibroblast lines incorporated a mean of 6.89 nanoatoms ¹⁴C/mg protein from 1-¹⁴C]propionate into trichloroacetic acid (TCA)-precipitable cell material in 10h. Twenty-five mutant fibroblast lines from patients with propionicacidemia or one of the methylmalonicacidemias fixed 0.04 to 0.93 nanoatoms ¹⁴C/mg. Considerable variation was observed, both among and within discrete mutant classes, with respect to the residual amount of propionate pathway activity, possibly reflecting further molecular heterogeneity in these disorders.We applied this procedure to cultured amniotic cells from controls and 4 midtrimester pregnancies at risk for methylmalonicacidemia and diagnosed one fetus with a methylmalonyl CoA apomutase defect and 3 fetuses which were unaffected.Presented in part at the annual meeting of the Society for Pediatric Research, St. Louis, Missouri, April 1976.