串联质谱技术在脑发育落后病因诊断中的意义  

Values of tandem mass spectrometry in etiologic diagnosis of cerebral developmental retardation

作　　者：张建明[1] 顾学范[2] 邵新华[1] 宋小青[1] 韩连书[2] 叶军[2] 邱文娟[2] 高晓岚[2] 王瑜[2] 汪梅先[1] 

机构地区：[1]交通大学医学院附属新华医院儿内科,上海200092 [2]上海市儿科医学研究所

出　　处：《中华儿科杂志》2007年第12期932-936,共5页Chinese Journal of Pediatrics

摘　　要：目的探讨串联质谱技术(MS/MS)在脑发育落后病因诊断及疗效判断中的意义。方法应用串联质谱仪,对158例脑发育落后患儿进行血氨基酸谱和酰基肉碱谱定量检测,对检出的11例代谢性疾病患儿 MS/MS 结果、尿气相色谱/质谱检测(GC/MS)结果、临床表现及治疗后变化进行综合分析。结果 158例中,11例(7.0%)患儿确诊为遗传代谢性疾病,其中甲基丙二酸血症5例,丙酸血症2例,鸟氨酸氨甲酰转移酶缺乏症1例,枫糖尿病1例,苯丙酮尿症1例,生物素酶缺乏症1例。临床表现为智能及运动发育落后或倒退(11例)、惊厥(5例)、昏迷(4例)、呕吐(4例)、营养不良(4例)、嗜睡(3例)、反复感染(3例)、肌张力降低(2例)等。实验室检查显示代谢性酸中毒、血氨及血乳酸增高、贫血等。MRI 表现为脑萎缩、双侧脑白质 T_2W 高信号或伴 T_1W 低信号、多发性脑软化或囊样变等。起病早、伴严重酸中毒及昏迷的甲基丙二酸血症预后较差。患儿经维生素 B_(12)、左旋肉碱、特殊奶方、低蛋白饮食及生物素等治疗后,好转8例,死亡3例。结论串联质谱技术有助于脑发育落后的病因诊断及疗效判断。早期诊断及合理治疗可避免脑组织进一步损害,并改善预后。Objectives To investigate the values of tandem mass spectrometry（MS/MS） in etiologic diagnosis and understanding therapeutic effect in cerebral developmental retardation, and to help patients in early diagnosis, treatment and favorable prognosis. Methods One hundred and fifty-eight childhood patients with brain heteroplasia were tested from July 2004 to October 2006. The blood was collected on filter paper, punched and extracted into methanol solution with stable isotope labeled internal standards, then derivatized with butanolic-HC1. After preparation, the samples were analysed by tandem mass spectrometry. Eleven MS/MS-positive patients were further analyzed based on gas chromatography/mass spectrometry （GC/MS） analysis of urine, clinical course, and treatment outcome. Results Eleven of 158 patients （7.0%） with inborn metabolic error were confirmed, including five with methylmalonic acidemia, two with propionic acidemia, one with ornithine transcarbamylase deficiency, one with maple syrup urine disease, one with phenylketonuria, and one with biotinidase deficiency. Among them, five were male, six were female, aged from 4 days to 21 months. The clinical manifestations were diverse, including mental developmental retardation or regradation （ 11 cases ）, convulsion （ 5 cases ）, coma （ 4 cases ）, vomiting （ 4 cases ）, malnutrition（4 cases ）, lethargy （ 3 cases ）, repeated infection （ 3 cases ）, hypetonia （ 2 cases ）, etc. Laboratory findings showed metabolic acidosis, hyperammonemia, hyperlactacidemia, anemia, etc. MRI findings of the brain showed cerebral atrophy, a pattern of bilateral T2 W high signal intensity or/and T1W low signal intensity in cerebral white matter and multiple encephalomalacia or vesicular change, ect. In methylmalonic acidemia patients, the early onset with severe acidosis and coma have had a poor prognosis. Improvement was observed in 8 cases after treatment with vitamin B12, L-carnitine, special milk, low-protein diet or biotin, etc. However 3 MMA

关 键 词：光谱分析 质量 色谱法 气相 脑疾病 代谢性 

分 类 号：R748[医药卫生—神经病学与精神病学]