title: Stable isotope dilution analysis of 3-hydroxyisovaleric acid in amniotic fluid: contribution to the prenatal diagnosis of inherited disorders of leucine catabolism.
abstract: A quantitative assay for 3-hydroxyisovaleric acid in amniotic fluid was developed using D6-3-hydroxyisovaleric acid as an internal standard. 3-Hydroxyisovaleric acid was isolated by liquid partition chromatography and the amount determined by selected ion monitoring, ammonia chemical ionization gas chromatography-mass spectrometry of the trimethylsilyl derivatives. The concentration of 3-hydroxyisovaleric acid in ten normal amniotic fluid was 4.52 +/- 1.73 mumol/l. The level was elevated eight-fold in the amniotic fluid from a pregnancy resulting in the birth of a child with biotin-responsive multiple carboxylase deficiency. The stable isotope dilution assay of 3-hydroxyisovaleric acid in amniotic fluid is a rapid, sensitive and accurate method for the prenatal diagnosis of this disorder, and may be of value in the prenatal diagnosis of other inherited disorders of leucine catabolism.
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics; D000649:Amniocentesis; D000653:Amniotic Fluid / Q000201:enzymology*; D002262:Carboxy-Lyases / Q000172:deficiency; D005260:Female; D006801:Humans; D007930:Leucine / Q000378:metabolism*; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D014631:Valerates / Q000378:metabolism*
chemical_list: D014631:Valerates; C004961:beta-hydroxyisovaleric acid; D002262:Carboxy-Lyases; D007930:Leucine