Hydroxy acid metabolites of branched-chain amino acids in amniotic fluid.
A method is described in which ammonia chemical ionization gas chromatography-mass spectrometry was utilized in the selected ion monitoring mode to provide an accurate, selective approach to the quantification in amniotic fluid of a number of hydroxylated organic acids derived from the metabolism of the branched-chain amino acids. 2-Hydroxy-n-caproic acid was employed as an internal standard and the hydroxy acids were isolated from amniotic fluid by liquid partition chromatography and the trimethylsilyl derivatives were quantified. Normal values have been obtained for 2-hydroxyisovaleric acid, the sum of 2-hydroxyisocaproic acid and 2-hydroxy-3-methylvaleric acid, 2-methyl-3-hydroxybutyric acid, 3-hydroxyisovaleric acid and 2-ethyl-3-hydroxypropionic acid. The method also provides data on the concentration of methylmalonic acid. The concentration of 2-hydroxyisovaleric acid was not useful in the prenatal diagnosis of a fetus with maple syrup urine disease. Elevated concentrations of 2-methyl-3-hydroxybutyric acid as well as methylmalonic acid were found in the amniotic fluid of two fetuses with methylmalonic acidemia.
D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis; D000597:Amino Acids, Branched-Chain / Q000032:analysis / Q000378:metabolism*; D000653:Amniotic Fluid / Q000032:analysis*; D002208:Caproates / Q000032:analysis; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006880:Hydroxy Acids / Q000032:analysis*; D006885:Hydroxybutyrates / Q000032:analysis; D008375:Maple Syrup Urine Disease / Q000175:diagnosis*; D008764:Methylmalonic Acid / Q000032:analysis; D010421:Pentanoic Acids / Q000032:analysis; D011247:Pregnancy; D011296:Prenatal Diagnosis; D014631:Valerates / Q000032:analysis
D000597:Amino Acids, Branched-Chain; D002208:Caproates; D006880:Hydroxy Acids; D006885:Hydroxybutyrates; D010421:Pentanoic Acids; D014631:Valerates; C035864:2-hydroxyisovaleric acid; C004961:beta-hydroxyisovaleric acid; C007674:2-ethylhydracrylic acid; C016579:2-methyl-3-hydroxybutyric acid; C035865:2-hydroxy-3-methylvaleric acid; C019419:alpha-hydroxyisocaproic acid; D008764:Methylmalonic Acid