2009-2021年浙江省新生儿遗传代谢病基因型分析  

Genotypes of neonatal inherited metabolic diseases in Zhejiang Province from 2009 to 2021

作　　者：杨茹莱[1] 沈亚平 陈迟[1] 周莹[1] 徐艳华[1] 舒强[1] YANG Rulai;SHEN Yaping;CHEN Chi;ZHOU Ying;XU Yanhua;SHU Qiang(Department of Genetics and Metabolism,Children's Hospital Affiliated to Zhejiang University School of Medicine(National Clinical Research Center for Child Health),Hangzhou,Zhejiang 310052,China)

机构地区：[1]浙江大学医学院附属儿童医院遗传与代谢科(国家儿童健康与疾病临床医学研究中心),浙江杭州310052

出　　处：《预防医学》2022年第8期760-764,共5页CHINA PREVENTIVE MEDICINE JOURNAL

基　　金：浙江省重点研发计划(2021C03099)。

摘　　要：目的了解2009—2021年浙江省新生儿筛查确诊的遗传代谢病病例基因型特征和预后,为新生儿出生缺陷防治提供依据。方法通过浙江省新生儿疾病筛查中心数据库收集2009—2021年浙江省采用串联质谱法筛查确诊的遗传代谢病病例资料,分析发病率、患儿基因型及预后情况等。结果2009—2021年浙江省累计筛查确诊新生儿遗传代谢病1038例,总发病率为1/4535;氨基酸代谢障碍(AAD)、脂肪酸氧化障碍(FAOD)和有机酸代谢障碍(OAD)分别为400、342和296例,发病率为1/11767、1/13763和1/15902。疾病32种,其中AAD 13种、FAOD 8种、OAD 11种;苯丙酮尿症/四氢生物蝶呤缺乏症(PKU/BH4D)、原发性肉碱缺乏症(PCD)和甲基丙二酸血症(MMA)分别占三大类疾病首位,发病率为1/20827、1/24262和1/49030。789例进行基因检测,占全部确诊病例的76.01%,其中AAD、FAOD、OAD基因检测率分别为70.00%、83.04%和76.01%。PKU患儿以c.728G>A(p.R243Q)变异最常见,占29.17%;PCD患儿以c.1400C>G(p.S467C)变异最常见,占33.46%;合并型MMA患儿以c.609G>A(p.W203X)变异最常见,占40.00%;单纯型MMA患儿以c.1663G>A(p.A555T)变异最常见,占17.86%。治疗随访997例,占96.05%;智力与体格发育达到正常水平973例,占93.74%;死亡41例,占3.95%,其中AAD 9例、FAOD 15例和OAD 17例。结论2009—2021年浙江省筛查确诊新生儿遗传代谢病以PKU、PCD、MMA发病率较高,常见基因型变异分别为c.728G>A(p.R243Q)、c.1400C>G(p.S467C)和c.609G>A(p.W203X);病例大多预后良好;OAD病例死亡比例相对较高。Objective To investigate the genotypes and prognosis of infants with definitive diagnosis of inherited metabol⁃ic diseases during neonatal screening in Zhejiang Province from 2009 to 2021,so as to provide insights into the man⁃agement of birth defects.Methods The medical records of infants with definitive diagnosis of inherited metabolic dis⁃eases by tandem mass spectrometry during neonatal screening in Zhejiang Province from 2009 to 2021 were collected from the database created by Zhejiang Provincial Center for Neonatal Disease Screening.The prevalence,genotypes and prognosis of inherited metabolic diseases were analyzed.Results A total of 1038 infants were definitively diagnosed with inherited metabolic diseases in Zhejiang Province from 2009 to 2021,with an overall incidence rate of 1/4535.There were 400 infants with amino acid metabolic disorders(AAD),342 infants with fatty acid oxidation metabolic disor⁃ders and 296 infants with organic acid metabolic disorders(OAD),with incidence of 1/11767,1/13763 and 1/15902,respectively.There were 32 types of diseases,including 13 types of AAD,8 types of FAOD and 11 types of OAD iden⁃tified,and phenylketonuria and tetrahydrobiopterin deficiency(PKU/BH4D),primary carnitine deficiency(PCD)and meth⁃ylmalonic academia(MMA)were detected as the most common forms of AAD,FAOD and OAD,with incidence of 1/20827,1/24262 and 1/49030,respectively.A total of 789 infants received genetic testing(76.01%),and genetic testing was performed among 70.00%of infants with AAD,83.04%of infants with FAOD and 76.01%of infants with OAD.The c.728G>A(p.R243Q)variant was the most common mutation in infants with PKU(29.17%),c.1400C>G(p.S467C)vari⁃ant was the most common mutation in infants with PCD(33.46%),c.609G>A(p.W203X)variant was the most common mutation in infants with combined MMA(40.00%),and c.1663G>A(p.A555T)variant was the most common mutation in infants with MMA(17.86%).Among the 997 infants(96.05%)with successful follow-up,973 infants(93.74%)had nor⁃mal intelligence and phy

关 键 词：新生儿筛查 遗传代谢病 串联质谱 发病率 基因型 预后 

分 类 号：R722.11[医药卫生—儿科]