3-Hydroxydicarboxylic and 3-ketodicarboxylic aciduria in three patients: evidence for a new defect in fatty acid oxidation at the level of 3-ketoacyl-CoA thiolase

Abstract

Abstract Three patients presented with evidence of a fatty acid oxidation disorder. Analysis of urinary organic acids by gas chromatography/mass spectrometry demonstrated the presence of medium-chain (C6-C12) dicarboxylic, 3-hydroxydicarboxylic, and 3-ketodicarboxylic acids in all three urines. 3-Ketodicarboxylic aciduria is reported for the first time here, as are the mass spectra for 3-ketosuberic, 3-ketosebacic, and 3-ketododecanedioic acids and the oximated spectrum for 3-ketoadipic acid. The presence of 3-ketodicarboxylic acids suggests a defect at the level of a long-chain 3-ketoacyl-CoA thiolase, an enzyme for which a deficiency state has not previously been described. Our patients may represent the first cases of a long-chain thiolase defect.