石家庄地区枫糖尿病患儿串联质谱筛查及BCKDHA、BCKDHB、DBT基因突变分析  

Tandem Mass Spectrometry Screening and BCKDHA,BCKDHB,and DBT Genetic Mutation Analysis in Children with Maple Syrup Urine Disease in Shijiazhuang Area,China

作　　者：贾立云 弓苗 杨会欣 王熙 封纪珍 JIA Li-yun;GONG Miao;YANG Hui-xin;WANG Xi;FENG Ji-zhen(Department of Genetics,Shijiazhuang Maternal and Child Health Hospital,Shijiazhuang 050000,China)

机构地区：[1]石家庄市妇幼保健院遗传科,050000

出　　处：《国际生殖健康／计划生育杂志》2023年第3期203-205,210,共4页Journal of International Reproductive Health/Family Planning

摘　　要：目的:了解中国河北省石家庄地区新生儿中枫糖尿病(maple syrup urine disease,MSUD)的患病率,分析相关基因突变特点。方法:采用串联质谱技术对石家庄地区2014年1月—2021年12月出生的185683例新生儿进行MSUD筛查,对筛查阳性患儿进行BCKDHA、BCKDHB、DBT基因突变检测。结果:确诊2例MSUD患儿,患病率为1∶92842。2例患儿的初筛及例2复查串联质谱血液亮氨酸、缬氨酸水平升高,例1因召回复查前已夭折,无复查串联质谱结果。确诊2例MSUD患儿均为经典型,分别检测到BCKDHB和DBT基因复合杂合突变,基因突变分析发现了4种突变位点:c.331C>T、c.289G>T、c.75_76delAT及c.1359_1360delAG;其中c.289G>T和c.1359_1360delAG为未报道基因突变,未检测到BCKDHA基因突变位点。例1于生后10 d夭折;例2于生后8 d开始出现症状,及时干预治疗后好转。结论:串联质谱技术应用于新生儿疾病筛查可及早发现MSUD患儿;相关基因检测可明确遗传学病因,为遗传咨询提供依据;石家庄地区MSUD的患病率为1∶92842;发现的4种基因突变位点中2种为未报道基因突变,丰富了基因突变谱。Objective:To explore the prevalence rate of maple syrup urine disease(MSUD)in newborns,and to analyze the mutation characteristics of related genes in Shijiazhuang area,China.Methods:A total of 185683 newborns born from January 2014 to December 2021 in Shijiazhuang area were screened for MSUD by tandem mass spectrometry,and BCKDHA,BCKDHB and DBT mutations were detected in newborns with positive screening.Results:Two children with MSUD were confirmed,with a prevalence rate of 1∶92842.In two confirmed cases,the levels of blood leucine(Leu)and valine(Val)were elevated during initial screening.The levels of case 2 were also elevated in the review of tandem mass spectrometry,while case 1 died prematurely before being recalled for review and was not performed the review of tandem mass spectrometry.Two children with MSUD were all classic with gene complex heterozygous mutations of BCKDHB and DBT,and four mutations were found including c.331C>T,c.289G>T,c.75_76delAT and c.1359_1360delAG.Two unreported gene mutations were found,c.289G>T and c.1359_1360delAG.No mutations in the BCKDHA gene were detected.Case 1 died prematurely 10 days after birth.Case 2 began to develop symptoms 8 days after birth,and improved after timely intervention and treatment.Conclusions:Tandem mass spectrometry technology can be applied in newborn disease screening to detect early newborns with MSUD.The genetic testing can identify genetic causes and provide a basis for genetic counseling.The prevalence rate of MSUD in Shijiazhuang area was 1∶92842.Four gene mutations,two of which were unreported gene mutations,were found in this study,enriching the gene mutation spectrum of MSUD.

关 键 词：枫糖尿病 氨基酸代谢障碍 先天性 新生儿筛查 串联质谱法 DNA突变分析 

分 类 号：R725.8[医药卫生—儿科]