串联质谱技术在有机酸血症筛查中的应用研究  

Application of tandem mass spectrometry in diagnosis of organic acidemias

作　　者：韩连书[1] 高晓岚[1] 叶军[1] 邱文娟[1] 顾学范[1] 

机构地区：[1]上海第二医科大学附属新华医院上海市儿科医学研究所内分泌,遗传代谢病研究室,200092

出　　处：《中华儿科杂志》2005年第5期325-330,共6页Chinese Journal of Pediatrics

基　　金：上海市科委科技攻关项目(024119021)

摘　　要：目的探讨串联质谱技术在遗传性代谢病高危儿童有机酸血症筛查和诊断中的意义。方法遗传性代谢病高危儿童1000例,男642例,女358例,年龄中位数为2岁(5天～15岁),手指采血,滴于滤纸片上。取直径3mm的干血滤纸片放入96孔聚丙烯板,经含酰基肉碱内标的甲醇萃取,盐酸正丁醇衍生后,进行串联质谱分析。结果1000例高危儿童中筛查并诊断有机酸血症40例(4.0%),其中甲基丙二酸血症20例,丙酸血症6例,异戊酸血症3例,戊二酸血症Ⅰ型3例,戊二酸血症Ⅱ型3例,3甲基巴豆酰辅酶A羧化酶缺乏症1例,3羟基3甲基戊二酰辅酶A裂解酶缺乏症1例,生物素酶缺乏症2例,β酮硫解酶缺乏症1例。患儿临床表现主要为运动和智力发育落后、抽搐、意识障碍、肌张力低下、呕吐和喂养困难等。常规实验室检查主要表现为酸中毒、高血氨、高乳酸血症和低血糖等。结论串联质谱技术能够通过检测血滤纸片中的不同酰基肉碱浓度,对部分有机酸血症进行快速筛查和诊断,结合尿气相色谱/质谱技术,有助于提高有机酸血症诊断的准确性。Objective The diagnosis of organic acidemia is very difficult and needs special test methods. Recently the tandem mass spectrometry has been used in screening for and diagnosis of this inborn error of metabolism. The aim of the present study was to utilize a dry blood filter paper method for acylcarnitines profiles test using tandem mass spectrometry in diagnosis of organic acidemias in high risk children.Method One thousand patients (642 were males and 358 females) with high risk of inborn error of metabolism were studied, the median of their age was 2 years. The blood specimens were collected on filter paper, punched and extracted into methanol solution with stable isotope labeled internal standards of acylcarnitine, then derivatized with butanolic-HCI. After preparation, the samples were analyzed by tandem mass spectrometry. The volume of the acylcarnitines was calculated with special software. Results Forty patients (4.0%) were diagnosed as organic acidemias among the 1000 patients, including 20 methylmalonic acidemia, 6 propionic acidemia, 3 isovaleric acidemia,3 glutaric acidemia type I, 3 glutaric acidemia type Ⅱ, 2 biotinidas deficiency, 1 3-methylcrotonyl-CoA carboxylase deficiency,1 3-hydroxy-3-methylglutaryl-CoA lyase deficiency, and 1 beta-keto thiolase deficiency. The common clinical symptoms and signs of these patients were motor and mental developmental retardation, spasm, lethargy, coma, hypotonia, vomiting, and feeding difficulty. Routine laboratory tests suggested metabolic acidosis, hyperammonemia, hyperlactacidemia, hypoglycemia, anemia, and abnormal liver function. Conclusion A part of organic acidemias can be rapidly diagnosed by tandem mass spectrometry through acylcarnitine profiles analysis in dry blood filter paper. Combination of tandem mass spectrometry with urine gas chromatography mass spectrometry would improve more accurate diagnosis of organic acidemias.

关 键 词：串联质谱技术 有机酸血症 遗传性代谢病 甲基丙二酸血症 生物素酶缺乏症 高危儿童 肌张力低下 实验室检查 高乳酸血症 滤纸片 手指采血 质谱分析 丙酸血症 发育落后 临床表现 意识障碍 喂养困难 主要表现 肉碱浓度 快速筛查 

分 类 号：R725.8[医药卫生—儿科]