气相色谱-质谱技术检测3 377例疑似遗传代谢病患儿的结果分析

Gas chromatography-mass spectrometry for detecting 3 377 patients with suspected inherited metabolic disorders

摘要:

目的：应用气相色谱质谱技术（gas chromatography-mass spectrometry，GC-MS）对疑似遗传代谢病（inherited metabolic disorders，IMDs）患儿进行检测分析，初步探讨遗传代谢病在重庆地区的发病情况。方法：采用GC-MS对重庆医科大学附属儿童医院2016年5月至2018年5月间的3 377例疑似IMDs患儿进行尿有机酸分析，通过尿有机酸检测结果，并结合患儿临床表现、串联质谱及基因结果进行疾病诊断；通过查阅既往病史或电话访问患儿家属获得患儿的发病年龄并进行统计。结果：检出并确诊阳性患儿69例，共20种IMDs，阳性检出率2.04%。其中，氨基酸代谢病30例，以新生儿肝内胆汁淤积症（neonatal intra－hepatic cholestasis caused by citrin deficiency，NICCD）最常见（17，56.7%），其次为鸟氨酸氨甲酰基转移酶缺乏症（ornithine tran－scarbamylase deficiency，OTCD）（9，30%）；有机酸代谢病26例，以甲基丙二酸血症（methylmalonic acidemia，MMA）最常见（13，46.4%），其次为戊二酸血症I型（glutaric acidemia type I，GA-I）（4，14.3%）及丙酸血症（propionic acidemia，PA）（3，10.7%）；脂肪酸代谢病11例，以多种酰基辅酶A缺乏症（multiple acyl-CoA dehydrogenase deficiency，MADD）最常见（4，36.4%）。在6种常见IMDs中，除7例MMA及1例NICCD、1例GA-I、1例PA患儿的发病年龄在出生后1个月内，其余40例患儿的发病年龄均超过1个月。结论：IMDs并不少见，NICCD、OTC、MMA、GA-I、PA及MADD是重庆地区最常见的遗传代谢病，以新生儿期后起病的患者更多见。

Abstract:

Objective：To detect the inherited metabolic disorders（IMDs） by gas chromatography-mass spectrometry（GC-MS） and to preliminarily investigate the prevalence of IMDs in Chongqing. Methods：A total of 3 377 patients with suspected IMDs in our hospital from May 2016 to May 2018 were underwent the urine organic acid analysis via GC-MS. According to the detecting results and combining with patients’ clinical manifestation，liquid chromatography tandem mass spectrometry（LC-MS/MS） and gene analysis to diagnose the disease；patients’ onset age was obtained by looking through medical history or telephoning their parents. Results：There were 69 patients diagnosed as positive and 20 kinds of IMDs，with a positive detection rate of 2.04%. Among all disorders，there were 30 patients with aminoacidopathy，with the most common one of neonatal intrahepatic cholestasis caused by citrin defi－ciency（NICCD）（17，56.7%） and followed by ornithine tran－scarbamylase deficiency（OTCD）（9，30%）. There were 26 pa－tients with organic acidemias，with the most common one of methylmalonic acidemia（MMA）（13，46.4%），followed by glutaric acidemia type Ⅰ（GA-Ⅰ）（4，14.3%） and propionic acidemia（PA）（3，10.7%）. There were 11 patients with fatty acid metabolic disease，with the most common one of multiple acyl-CoA dehydro－genase deficiency（MADD）（4，36.4%）. Among the six common disorders，40 patients’ onset age was more than one month，except seven patients with MMA，one patient with NICCD，one patient with GA-I and patient with PA. Conclusion：IMDs are not rare，and NICCD，OTCD，MMA，GA-I，PA and MADD are the common disorders in Chongqing，which occurs more frequently in the late neonatal period.