Matsumoto M, Matsumoto I, Shinka T, Kuhara T, Imamura H, Shimao S, Okada T
Division of Human Genetics, Kanazawa Medical University, Ishikawa, Japan.
Acta Paediatr Jpn. 1990 Feb;32(1):76-82. doi: 10.1111/j.1442-200x.1990.tb00787.x.
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.
采用气相色谱 - 质谱联用技术和快原子轰击质谱法对一名2个月大男婴的尿中有机酸和酰基肉碱谱进行了研究。该患者排泄出大量戊二酸以及大量3 - 羟基戊二酸、戊烯二酸和戊二酰肉碱，其血清戊二酸水平显著升高。因此，他被化学诊断为I型戊二酸血症（GAI）。除了先前在GAI中描述的上述代谢产物外，还发现2 - 酮戊二酸、琥珀酸、己二酸、己二酰肉碱、辛二酸和壬二酸的排泄量显著增加。尿中也可检测到2 - 酮己二酸、甲基琥珀酸和乙基丙二酸，辛二酰肉碱未增加，脱氢己二酰肉碱减少。这些结果表明，过量的戊二酰辅酶A导致己二酰辅酶A脱氢生成脱氢己二酰辅酶A的竞争性抑制，从而导致己二酸和己二酰肉碱增加，脱氢己二酰肉碱减少。还表明，高水平的戊二酰辅酶A抑制了2 - 酮戊二酸氧化脱羧生成琥珀酰辅酶A，并且由于过量戊二酰辅酶A衍生的戊二酸增加，琥珀酸脱氢生成富马酸的过程受到抑制。这些结果表明，气相色谱 - 质谱联用技术是GAI和II型戊二酸血症鉴别化学诊断中最合适、最准确的方法。
