南宁市部分地区新生儿遗传代谢病疾病谱和基因谱特征分析  

Disease spectrum and genetic profiles of neonatal inborn errors of metabolism in selected areas of Nanning city

作　　者：覃晓 旷娟 蓝国锋 曾贵祥[2] 古玉芳 史学凯[1] Qin Xiao;Kuang Juan;Lan Guofeng;Zeng Guixiang;Gu Yufang;Shi Xuekai(Department of Pediatrics,the Second Nanning People's Hospital,Nanning 530031,China;Department of Pediatrics,Nanning Maternal and Child Health Hospital,Nanning 530028,China;Department of Pediatrics,Sixth People's Hospital of Nanning,Nanning 350001,China)

机构地区：[1]南宁市第二人民医院儿科,南宁530031 [2]南宁市妇幼保健院儿科,南宁530028 [3]南宁市第六人民医院儿科,南宁350001

出　　处：《中华新生儿科杂志（中英文）》2023年第5期289-293,共5页Chinese Journal of Neonatology

基　　金：南宁市科技局重大专项科研(2019-3091)。

摘　　要：目的分析南宁市部分地区新生儿遗传代谢病疾病谱和基因谱的特征。方法选择2019年7月至2021年12月在南宁市第二人民医院出生并进行多种遗传代谢病筛查的新生儿进行前瞻性研究。取新生儿足跟血后采用串联质谱法进行初筛,初筛阳性者予召回后复查串联质谱并进行生化和影像学检查,采用医学全外显子组测序技术对疑似病例进行遗传病基因检测,最后结合临床表现进行确诊,并采用Sanger测序法对确诊患儿及其父母的基因变异进行验证。结果共16207名新生儿接受遗传代谢病筛查,初筛阳性1423例(8.8%),召回新生儿1311例,召回率92.1%,疑似病例15例,确诊8例,总体检出率为1∶2026。包括氨基酸代谢病4例(苯丙酮尿症2例、希特林蛋白缺乏症和酪氨酸血症各1例),有机酸代谢病2例(甲基丙二酸血症和戊二酸血症各1例),脂肪酸氧化障碍疾病2例(肉碱棕榈酰转移酶Ⅱ缺乏症和原发性肉碱缺乏各1例),其中纯合基因变异5例,分别为PAH基因2例,SLC25A13基因、SLC22A5基因、FAH基因各1例;杂合基因变异3例,分别为CPT2基因、MUT基因、GCDH基因各1例。8例患儿经规范治疗及随访,均生长发育良好。结论南宁市部分地区新生儿遗传代谢病检出率较高、种类较多,及时行基因检测可早期诊断及治疗,改善患儿生存质量。Objective To study disease spectrum and genetic profiles of inborn errors of metabolism(IEM)among newborns in selected areas of Nanning city.Methods From July 2019 to December 2021,neonates born and received IEM screening in our hospital were prospectively enrolled.Heel blood samples were tested using tandem mass spectrometry as IEM screening.Neonates with positive results were called back for recheck.Whole exome sequencing was used to detect possible pathogenic genes in suspected cases and IEM was diagnosed combining clinical manifestations.Sanger sequencing method was used for the diagnosed neonates and their parents to confirm the diagnoses.Results A total of 16207 live-birth neonates were enrolled.For initial IEM screening,1423 neonates were positive(8.8%)and 1311 were called back(92.1%).15 cases were suspected with IEM and 8 were diagnosed.The overall detection rate was 1∶2026.Among 8 confirmed cases,4 cases had amino acid metabolism disorders(2 cases of phenylketonuria,1 case of Citrin deficiency and 1 case of tyrosinemia),2 cases had organic acid metabolism disorders(1 case of methylmalonic acidemia and 1 case of glutaric acidemia)and 2 cases had fatty acid oxidation disorders(1 case of carnitine palmitotransferaseⅡdeficiency and 1 case of primary carnitine deficiency).5 cases had homozygous genetic variants(2 in PAH,and 1 in SLC25A13,SLC22A5 and FAH,respectively)and 3 had heterozygous genetic variants(1 in CPT2,MUT,and GCDH,respectively).During follow-up,all 8 cases had normal growth and developmental outcomes after standardized treatment.Conclusions The overall detection rate of IEM is high,with varied genetic profiles in selected areas of Nanning.Timely genetic testing may lead to early diagnosis and treatment and improve the quality of life of neonates.

关 键 词：新生儿筛查 遗传代谢病 串联质谱 基因检测 

分 类 号：R722.11[医药卫生—儿科]