Prenatal diagnosis of propionic acidemia

Prenatal diagnosis of a fetus with propionic acidemia has been accomplished by the detection of methylcitrate, a unique metabolite, in the amniotic fluid by liquid partition chromatography and gas chromatography-mass spectrometry. The diagnosis was confirmed by demonstration of deficient activity of propionyl-CoA carboxylase in cells cultured from the amniotic fluid and in fetal tissues. In two subsequent pregnancies, methylcitrate was not present in amniotic fluid. Enzyme assay indicated that one fetus was heterozygous and the other was normal, and healthy infants were born at term. The analysis of organic acids in amniotic fluid permits very rapid prenatal diagnosis, usually within 48 hours after obtaining the fluid. It may provide a general method in conditions in which an unusual metabolite can be identified.