Prenatal diagnosis of glutaric aciduria type II by direct chemical analysis of dicarboxylic acids in amniotic fluid.

A method for the measurement of dicarboxylic acids in amniotic fluid was developed that utilizes isolation of the acids by liquid partition chromatography and quantification by ammonia chemical ionization selected ion monitoring, gas chromatography-mass spectrometry. The concentrations of dicarboxylic acids in ten normal samples of amniotic fluid (mumol/l +/- 1 S.D.) were glutaric acid 0.91 +/- 0.15, adipic acid 0.33 +/- 0.08, suberic acid 0.27 +/- 0.08, and sebacic acid 0.21 +/- 0.10. A highly elevated concentration of 14.48 mumol/l glutaric acid was found in the amniotic fluid of a pregnancy in which the fetus was affected with glutaric aciduria type II. Adipic, suberic and sebacic acids were also significantly elevated. The dicarboxylic acids were normal in the amniotic fluid of a pregnancy at risk for glutaric aciduria type II in which the fetus was unaffected. This method is suitable for the rapid prenatal diagnosis of glutaric aciduria types I and II and of potential value for the prenatal diagnosis of other inherited disorders in which dicarboxylic acids accumulate.