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目的通过尿素酶预处理-气相色谱-质谱法(UP-GC-MS)检测1 330例高危儿遗传性代谢病(IMD)及代谢紊乱的发病率,为临床诊断和治疗提供依据。方法留取出生1 d～3岁高危儿尿液样本,尿液标本经尿素酶去尿素、加内标、除蛋白、真空干燥处理、残余物用双(三甲基硅烷基)三氟乙酰胺/三甲基氯硅烷衍生后进样,应用气相色谱-质谱联用仪分析其尿液中有机酸、氨基酸、糖类、多醇、嘌呤和嘧啶等成分。结果 1 330例高危儿中,共890例(66.9%)存在代谢异常。其中确诊IMD 21例(1.6%),包括甲基丙二酸尿症8例,高苯丙氨酸血症3例,尿素循环障碍、半乳糖血症、枫糖尿症、异戊酸血症和丙酸血症各2例;疑似IMD 49例(3.7%),包括酪氨酸血症23例、脂肪酸代谢障碍12例、尿素循环异常8例和Citrin缺陷症6例,其中4例经过串联质谱检测和基因分析得到确诊;确诊非遗传因素所致代谢病40例(3.0%),包括乳酸血症28例及甘油尿症12例;此外,还有780例(58.6%)高危儿存在代谢紊乱,表现为尿半乳糖、4羟基苯乳酸、N-乙酰酪氨酸、乳酸、乳糖、琥珀酸、酮性双羧酸水平增高以及丝氨酸/苏氨酸比例异常。结论 UP-GC-MS是诊断小儿IMD和代谢紊乱的有效方法,必要时应联合应用串联质谱检测及基因分析进行诊断。
Objective To investigate the prevalence of hereditary metabolic diseases (IMD) and metabolic disorders in 1 330 high-risk infants by urease preconditioning-gas chromatography-mass spectrometry (UP-GC-MS) and provide the basis for clinical diagnosis and treatment. Methods Urine samples from 1 to 3 years old were collected from urine samples. Urine samples were treated with urease to remove urea, add internal standard, remove protein and vacuum dried. The residue was treated with bis (trimethylsilyl) trifluoroacetamide / Trimethylchlorosilane derived from the sample, the application of gas chromatography - mass spectrometry urine analysis of organic acids, amino acids, sugars, polyols, purine and pyrimidine and other ingredients. Results Among 1 330 high risk infants, a total of 890 patients (66.9%) had metabolic abnormalities. The diagnosis of IMD in 21 cases (1.6%), including 8 cases of methylmalonic aciduria, hyperphenylalaninemia in 3 cases, urea cycle disorders, galactosemia, maple syrup urine, isovaleratemia and 2 cases of propionic acidemia; 49 cases suspected of IMD (3.7%), including 23 cases of tyrosinemia, fatty acid metabolism in 12 cases, 8 cases of abnormal urea circulation and Citrin deficiency in 6 cases, of which 4 cases after tandem mass spectrometry Detection and genetic analysis were confirmed; 40 cases (3.0%) were diagnosed as non-genetic metabolic diseases, including 28 cases of lactic acidosis and 12 cases of glyceroluria; In addition, there were 780 cases (58.6%) of high-risk infants with metabolic disorders , Manifested as urinary galactose, 4-hydroxybenzene lactic acid, N-acetyl tyrosine, lactic acid, lactose, succinic acid, ketocarboxylic acid levels increased and serine / threonine anomalies. Conclusion UP-GC-MS is an effective method to diagnose IMD and metabolic disorders in children. If necessary, UP-GC-MS should be combined with tandem mass spectrometry and gene analysis.