遗传性代谢病高危婴幼儿4710例尿素酶预处理-气相色谱-质谱技术筛查分析

Screening analysis of 4 710 cases of inherited metabolic diseases in high - risk infants using urease pretreat-ment-gas chromatography-mass spectrometry

目的：通过尿素酶预处理-气相色谱-质谱法（UP-GC-MS）检测4710例高危婴幼儿遗传性代谢病（IMD）及代谢紊乱的发病率，为临床诊断和治疗提供依据。方法对高危婴幼儿尿液样本经过去尿素、加内标、除蛋白、真空干燥、三甲基硅烷基衍生等处理后，应用尿素酶预处理-气相色谱-质谱联用仪分析尿液中有机酸、氨基酸、糖类、多醇、嘌呤和嘧啶等成分，以健康儿童色谱质谱检测值作为参考值，分析质谱检测结果，并进行代谢分析，最后结合临床高危表现和一般生化检测及其他特殊检查等临床资料进行代谢诊断。结果4710例高危儿中，确诊 IMD 98例（2.1％）、疑诊 IMD 患儿326例（6.9％）、代谢异常患儿2610例（55.4％），其余1676例未见异常。其中确诊 IMD 包括甲基丙二酸尿症57例，丙酸血症12例，戊二酸血症7例，高苯丙氨酸血症、枫糖尿症和多种羧化酶缺陷症各5例，异戊酸血症4例，4羟基丁酸尿症3例。结论 UP-GC-MS 是诊断高危婴幼儿 IMD 和代谢紊乱的有效方法，广东地区常见的 IMD 为甲基丙二酸尿症、丙酸血症、戊二酸血症、高苯丙氨酸血症、枫糖尿症和多种羧化酶缺陷症，检测结果可为患儿的诊断和治疗提供有效指导。

Objective To detect the incidence of inherited metabolic diseases（IMD）and disorders of metabo-lism in 4 710 high - risk infants,as well as providing basis of clinical diagnosis and treatment by using urease pretreat-ment - gas chromatography - mass spectrometry（UP - GC - MS）. Methods Samples were collected from high - risk infants with IMD,after removing urea,putting in internal standard,removing protein,vacuum drying and bis （trimethyl - silyl）trifluoroacetamide / trimethyl - chlorosilane derivativing,UP - GC - MS was used to analyze compo-sitions such as organic acids,amino acids,carbohydrates,pyridoxines,purines and pyrimidines,then metabolic analysis was proceeded to refer to the normal detection value of the healthy children,finally a metabolic diagnosis was made ba-sing on the clinical data such as the high - risk clinical manifestations and general biochemical tests and other special examinations. Results In the 4 710 cases,there were 98 cases of IMD（2. 1% ）,326 cases of suspected IMD（6. 9% ）, 2 610 cases of metabolic disorders（55. 4% ）. There were 98 cases of IMD,including 57 cases of methylmalonic aciduria,12 cases of propionic acidemia,7 cases of glutaric aciduria,5 cases of hyperphenylalaninemia,maple syrup u-rine disease and multiple carboxylase defects each,4 cases of isovaleric acidemia and 3 cases of 4 - hydroxy butyric acid urine disease. Conclusions UP - GC - MS is a effective way to diagnose IMD and metabolic disorders of infants. Common IMD in Guangdong Province include methylmalonic aciduria,propionic academia,glutaric aciduria,hyperphe-nylalaninemia,maple syrup urine disease and multiple carboxylase defects. The results of the tests can provide effective guidance for diagnosis and treatment of suspected infants.