气相色谱-质谱联用技术在遗传代谢性疾病诊断中的应用

Role of gas chromatography-mass spectrometry in inherited metabolic diseases

目的探讨气相色谱-质谱联用(GC-MS)技术在遗传代谢病诊断中的应用。方法收集5778例疑似遗传代谢病患儿的尿液,经萃取、衍生后采用GC-MS技术检测132种代谢产物,通过遗传代谢病分析软件并结合实验室其他检测等进行诊断。结果5778例疑似患儿尿液样本中有1100例(19%)有异常代谢产物,共有106例患儿被明确诊断出17种疾病,其中尿液中特征性指标异常的患儿80例、结合血串联质谱结果确诊26例患儿。80例尿液出现特征性指标异常的患儿中有机酸代谢障碍疾病患儿65例,确诊疾病11种;氨基酸代谢障碍疾病患儿15例,确诊疾病3种;包括甲基丙二酸血症33例、高苯丙氨酸血症12例、丙酸血症7例、戊二酸血症Ⅰ型7例、尿素循环障碍6例、β酮硫解酶缺乏症3例、乙基丙二酸血症2例、枫糖浆尿症2例、异戊酸血症2例、多种羧化酶缺乏症2例、酪氨酸血症Ⅰ型1例、2-羟基戊二酸血症1例、3-甲基巴豆酰辅酶A羧化酶缺乏症1例、3-羟基-3-甲基戊二酸尿症1例。结合血串联质谱结果确诊的26例患儿中希特林蛋白缺乏症19例、极长链酰基辅酶A脱氢酶缺乏症5例、中链酰基辅酶A脱氢酶缺乏症2例。结论GC-MS技术对有机酸代谢异常和部分氨基酸代谢异常诊断有特异性。GC-MS技术检测结果影响因素多,但对疾病最终诊断无影响。

Objective To investigate the application of gas chromatography-mass spectrometry(GC-MS) in the diagnosis of inherited metabolic diseases. Methods Urine samples of 5 778 children with suspected inherited metabolic diseases were enrolled. After extraction and derivatization,132 metabolites were detected by GS-MS and analyzed by inherited metabolic disease analysis software. Combined with other laboratory tests,the diagnosis was performed. Results Of the 5 778 urine samples,1 100 cases had abnormal metabolites, accounting for 19%. A total of 106 cases with 17 diseases were diagnosed,among which 80 cases were diagnosed with abnormal characteristics in urine,and 26 cases were diagnosed with blood tandem mass spectrometry. Among the 80 cases,there were 65 cases with 11 types of organic acid metabolic disorders and 15 cases with 3 amino acid metabolic disorders,including 33 cases of methylmalonicmia,12 cases of hyperphenylalaninemia,7 cases of propionic acidemia,7 cases of glutaric acidemia typeⅠ,6 cases of urea circulatory disorders,3 cases of β-ketothiolase deficiency,2 cases of methylmalonic acidemia,2 cases of maple syrup urine disease,2 cases of isovaleric acidemia,2 cases of multiple carboxylase deficiency,1 case of tyrosinemia type Ⅰ,1 case of 2-hydroxyglutaratemia,1 case of 3-methylcrotonyl- CoA carboxylase deficiency and 1 case of 3-hydroxy-3-methylglutaric acidemia. Totally,26 cases were diagnosed by tandem mass spectrometry,including 19 cases of Citrin deficiency,5 cases of very long-chain acyl-CoA dehydrogenase deficiency and 2 cases of medium-chain acyl-CoA dehydrogenase deficiency. Conclusions GC-MS is specific for the abnormality of organic acids and partial amino acid metabolism abnormality. The results of GC-MS are influenced by many factors,but it has no difference in clinical judgment.