Organic Acid and Acylcarnitine Profiles of Glutaric Aciduria Type I

Abstract

Urinary organic acid and acylcarnitine profiles from a 2-month-old boy were studied by gas chromatography-mass spectrometry and fast atom bombardment mass spectrometry. The patient excreted large amounts of glutaric acid and significant amounts of 3-hydroxyglutaric acid, glutaconic acid and glutarylcarnitine, and his serum glutaric acid level was markedly elevated. Thus he was chemically diagnosed as having glutaric aciduria type I (GAI). In addition to the above metabolites previously described in GAI, significantly increased excretion of 2-ketoglutaric acid, succinic acid, adipic acid, adipylcarnitine, suberic acid and azelaic acid was found. 2-Ketoadipic acid methylsuccinic acid and ethylmalonic acid were also detectable, suberylcarnitine was not increased, and dehydroadipylcarnitine was decreased in his urine. These results suggest that excess glutaryl-CoA causes the competitive inhibition of the dehydrogenation of adipyl-CoA to dehydroadipyl-CoA and results in an increase of adipic acid and adipylcarnitine and a decrease of dehydroadipylcarnitine. It is also suggested that oxidative decarboxylation of 2-ketoglutaric acid to succinyl-CoA is inhibited by high levels of glutaryl-CoA, and that the dehydrogenation of succinic acid to fumaric acid is inhibited owing to the increased glutaric acid derived from excess glutaryl-CoA. These results indicate that gas chromatography-mass spectrometry is the most appropriate and accurate method for the differential chemical diagnosis of GAI and glutaric aciduria type II.