新疆地区新生儿遗传代谢病筛查诊断结果分析  

Analysis of newborn screening and diagnosis of inherited metabolic diseases in Xinjiang

作　　者：朱静潆 韩丽 陈琪 杨苹靖文 冯子奕 薛淑媛 ZHU Jingying;HAN Li;CHEN Qi;YANG Pingjingwen;FENG Ziyi;XUE Shuyuan(Prenatal Diagnosis Center,Urumqi Maternal and Child Healthcare Hospital,Urumqi,Xinjiang 830000,China;Xinjiang Clinical Medical Research Center for Perinatal Diseases,Urumqi,Xinjiang 830000,China;School of Medicine,Shihezi University,Shihezi,Xinjiang 832000,China)

机构地区：[1]乌鲁木齐市妇幼保健院产前诊断中心,新疆乌鲁木齐830000 [2]新疆围产期疾病临床医学研究中心,新疆乌鲁木齐830000 [3]石河子大学医学院,新疆石河子832000

出　　处：《中国优生与遗传杂志》2024年第8期1611-1617,共7页Chinese Journal of Birth Health & Heredity

基　　金：新疆维吾尔自治区“青年科技人才-乡村振兴”项目(WJWY-XCZX 202226)。

摘　　要：目的将串联质谱联合二代测序技术应用于新疆地区新生儿遗传代谢病的诊断,并初步获得新疆地区新生儿遗传代谢病的发病率、疾病谱和遗传特征。方法采用串联质谱技术对2018年11月至2022年12月乌鲁木齐市妇幼保健院的64980例新生儿干血斑样本进行遗传代谢病筛查,筛查阳性待确诊的婴儿需要进行进一步鉴别诊断,并采用高通量测序技术进行遗传学分析。结果初筛阳性的新生儿召回复查结果仍为阳性人数为232人,其中67人利用二代测序进一步诊断。最终42名新生儿和2名家系成员被确诊为遗传代谢病,总体的阳性预测值(PPV)18.10%。新疆地区新生儿遗传代谢病的总体发病率为1∶1547(42/64980)。氨基酸代谢异常、有机酸代谢异常和脂肪酸氧化障碍的发病率分别为1∶2320(28/64980)、1∶7220(9/64980)和1∶12996(5/64980)。苯丙酮尿症和甲基丙二酸血症是本地区最常见的IEM类型,占所有确诊新生儿的76%(32/42)。高苯丙氨酸血症PAH基因c.158G>A和c.688G>A点突变最为常见;发现了本地区甲基丙二酸血症MMACHC基因包括c.609G>A、c.567dupT、c.217C>T、c.445_446delTG四种突变类型;发现了MMUT基因c.729_730insT等的6种突变类型;发现了HPD、PCCB、IVD、GCDH、MCCC1、SLC22A5、ACADS这7种基因的16种突变类型。结论本研究联合串联质谱技术和二代测序技术,用于遗传代谢病的筛查与诊断,为新疆地区扩大新生儿筛查、基因筛查和IEM基因咨询的普及及应用提供了有效的临床指导与数据基础。Objective To explore the application value of tandem mass spectrometry combined with next-generation sequencing technology in the diagnosis of inborn errors of metabolism(IEM)in Xinjiang,China,and to explore the disease spectrum and genetic characteristics of IEM in Xinjiang,China.Methods Tandem mass spectrometry was used to screen 64980 neonatal dried blood spot samples from Urumqi Maternal and Child Healthcare Hospital from November 2018 to December 2022.Further differential diagnosis is required for infants who have tested positive for screening and are yet to be diagnosed,and use next generation sequencing for genetic analysis.Results The number of newborns who were initially screened positive was 232 who were still positive after recall,and 67 of them underwent NGS sequencing for further diagnosis.Finally,a total of 42 neonates and 2 family members were diagnosed with inherited metabolic diseases,with an overall positive predictive value(PPV)of 18.10%.The overall incidence of neonatal genetic metabolic diseases in Xinjiang was 1∶1547(42/64980).The incidences of abnormal amino acid metabolism,abnormal organic acid metabolism and fatty acid oxidation disorders were 1∶2320(28/64980),1∶7220(9/64980)and 1∶12996(5/64980),respectively.Phenylketonuria and methylmalonic acidemia are the most common types of IEM in the region,accounting for 76%(32/42)of all confirmed neonates.Hyperphenylalanineemia PAH gene c.158G>A and c.688G>A point mutations are the most common;Four mutation types of MMACHC gene including c.609G>A,c.567dupT,c.217C>T and c.445_446delTG were found in the MMACHC gene of methylmalonic acidemia in this region,and six mutation types including c.729_730insT were found in MMUT gene.And 16 mutation types in seven genes:HPD,PCCB,IVD,GCDH,MCCC1,SLC22A5,and ACADS.Conclusion In this study,tandem mass spectrometry and next-generation sequencing technology were used for the screening and diagnosis of inherited metabolic diseases,which provided effective clinical guidance and data basis for expanding the p

关 键 词：遗传代谢病 串联质谱技术 二代测序 

分 类 号：R722.1[医药卫生—儿科]