浙江省新生儿有机酸尿症筛查及随访分析

Screening for newborn organic aciduria in Zhejiang province:prevalence,outcome and follow-up

目的:了解浙江省新生儿有机酸尿症的患病率和确诊病例的发病情况及转归。方法:采用串联质谱技术对2009年1月至2016年12月浙江省1 861 262名新生儿进行酰基肉碱谱筛查,结合尿气相色谱—质谱及基因检测确诊,分析各有机酸尿症的患病率及临床随访情况。结果:确诊八种有机酸尿症92例(1:20 200)。甲基丙二酸血症40例(1:46 500),其中甲基丙二酸血症单纯型13例(32.5%),基因检测7例,6例为MUT型,1例CblB型;甲基丙二酸血症合并型27例(67.5%),基因检测11例,10例为CblC型,1例为CblF型。丙酸血症6例(1:310 200),异戊酸血症7例(1:265 900),戊二酸血症Ⅰ型6例(1:310 200),3-甲基巴豆辅酶A羧化酶缺乏症27例(1:68 900),3-羟基-3-甲基戊二酸尿症1例(1:1 861 300),β-酮硫解酶缺乏症2例(1:960 600),生物素酶缺乏症和全羧化酶合成酶缺乏症3例(1:620 400)。31例患儿于新生儿期发病,15例患儿于新生儿期后发病;33例有脑病或颅脑影像学异常,肾病或溶血尿毒综合征3例,心肌损害3例,死亡20例。结论:甲基丙二酸血症是浙江省新生儿筛查中最常见的有机酸尿症。除3-甲基巴豆辅酶A羧化酶缺乏症外,有机酸尿症患儿易发生代谢失代偿、并发症甚至死亡。

Objective：To analyze the results and follow up data of screening for newborn organic aciduria in Zhejiang province. Methods：The results and follow-up data of 1 861 262 newborns from Zhejiang province undergoing screening for organic aciduria during January 2009 and December 2016 were retrospectively analyzed. The acylcarnitine spectrum in urine samples was detected by tandem mass spectrum （MS/MS） and the positive patients were confirmed by urine gas chromatography mass spectrometry and/or gene analysis. Results：Ninety two cases of organic aciduria were confirmed with a prevalence of 1：20 200. Among 40 cases of methylmalonic academia （MMA）, 13 （32.5%） were of MMA simple type and 27 （67.5%） were combined type. Genetic analysis showed 6 cases of MUT type and 1 case of CblB type out of 7 patients with MMA simple type, 10 cases of CblC and 1 case of CblF out of 11 patients with combined type, respectively. Six patients had propionic academia with a prevalence of 1：310 200, 7 had isovaleric academia （1：265 900）, 6 had glutaric academia type 1 （1：310 200）, 27 had 3-methylcrotonyl-CoA carboxylase deficiency （MCC, 1：68 900）, 1 had 3-hydroxy-3-methylglutaric aciduria （1：1 861 300）, 2 had β-ketothiolase deficiency （1：960 600）, and 3 had biotinidase deficiency/holocarboxylase synthetase deficiency （1：620 400）. Thirty-one patients had a disease onset at neonatal period, and 15 at post-neonatal period. Thirty-three patients had brain involvements or cranial imaging disorders. Three patients with MMA had kidney diseases or heomlytic uremic syndrome, and 3 had myocardial impairments. Twenty patients died during the follow-up. Conclusion：MMA is the most common newborn organic aciduria in Zhejiang province. Except MCC, most organic aciduria may lead to metabolism decompensation, complications or even death.