葡萄糖-6-磷酸脱氢酶缺乏症新生儿葡萄糖-6-磷酸脱氢酶及其基因突变的研究  

Study on glucose-6-phosphate dehydrogenase and gene mutation in neonates with glucose-6-phosphate dehydrogenase deficiency

作　　者：郭静[1] 田国力[1] 王燕敏[1] 周卓[1] 纪伟 Guo Jing;Tian Guoli;Wang Yanmin;Zhou Zhuo;Ji Wei(Neonatal Screening Center,Children′s Hospital of Shanghai/Children′s Hospital of Shanghai Jiaotong University,Shanghai 200040,China)

机构地区：[1]上海市儿童医院/上海交通大学附属儿童医院新生儿筛查中心,200040

出　　处：《中华妇幼临床医学杂志（电子版）》2020年第6期672-679,共8页Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition)

基　　金：国家自然科学基金青年科学基金项目(21803009);上海市科学技术委员会科研项目(18441905100);上海市重中之重临床重点专科建设项目(2017ZZ02019)。

摘　　要：目的探讨葡萄糖-6-磷酸脱氢酶(G6PD)缺乏症新生儿G6PD与其基因突变情况。方法 2017年8月至2019年4月,在上海市儿童医院新生儿筛查中心进行G6PD缺乏症筛查的新生儿为105 766例,初筛G6PD缺乏症呈阳性患儿为217例,选择其中被召回进行G6PD复筛和(或)基因检测的161例新生儿为研究对象。这161例新生儿均接受G6PD复筛,其中146例接受G6PD基因检测。同时对男性患儿及其母亲、女性患儿及其父母(将男性患儿母亲与女性患儿父母统称为患儿家系成员)进行G6PD活性和基因检测,分析患儿及其家系成员G6PD活性、G6PD基因突变位点地域性分布特点,并分析G6PD活性与不同G6PD基因突变位点的关系。采用Mann-Whitney U检验或Kruskal-Wallis H秩和检验,对不同患儿与其家系成员的G6PD活性,以及不同G6PD基因突变位点患儿及其家系成员的G6PD活性进行比较。本研究研究遵循的程序符合2013年新修订的《世界医学协会赫尔辛基宣言》要求,并与患儿监护人签署临床研究知情同意书。结果 (1)本组联合实验室诊断和(或)基因诊断的结果,最终确诊的G6PD缺乏症新生儿为124例(经G6PD活性确诊为121例,G6PD基因检测确诊为113例,二者同时确诊为110例)。(2)经G6PD活性检测确诊为G6PD缺乏症的121例患儿中,男、女性患儿分别为103、18例。这121例患儿的G6PD活性为0.42 U/g血红蛋白(Hb)(0.35~0.67 U/g Hb),显著低于其家系成员的1.17 U/g Hb(0.91~1.42 U/g Hb),男性患儿G6PD活性为0.40 U/g Hb(0.32~0.53 U/g Hb),显著低于其母亲的1.12 U/g Hb(0.91~1.28 U/g Hb),女性患儿G6PD活性为1.16 U/g Hb(0.92~1.46 U/g Hb),显著低于其父母的1.74 U/g Hb(0.69~2.80 U/g Hb),并且上述差异均有统计学意义(Z=-9.981、-10.832、-2.021,P<0.001、<0.001、=0.043)。(3)本组161例受试儿中,共计146例患儿及其185例家系成员进行G6PD基因检测的结果显示,227例(113例患儿与114例患儿家系成员)携带G6PD基因突变,其中3例�Objective To explore the glucose-6-phosphate dehydrogenase(G6PD)and its gene mutation in G6PD deficiency neonates,and to provide reference for clinical diagnosis of G6PD deficiency infants.Methods A total of 105766 newborns screened at Neonatal Screening Center of Shanghai Children′s Hospital from August 2017 to April 2019 were collected.A total of 217 children were initially screened positive for G6PD deficiency,including 161 neonates who were recalled for re-screening for G6PD and/or G6PD gene mutations.And these 161 neonates were selected as research subjects.All of them received re-screening for G6PD,and 146 cases received G6PD gene mutation detection.The male children and their mothers,female children and their parents(the male children′s mothers and female children′s parents were collectively referred as family members of children)received quantitative analysis of G6PD enzyme activity and detection of G6PD gene mutation in children and their family members at the same time.The G6PD enzyme activity,G6PD gene mutation site and its regional distribution characteristics in children and their family members,and the relationship between G6PD enzyme activity and different G6PD gene mutation sites were analyzed.Mann-Whitney U test and Kruskal-Wallis H rank sum test were used for comparisons of G6PD enzyme activity between children and their family members,and relation between G6PD enzyme activity and different sites of G6PD gene mutation.The study was in accordance with the requirements of World Medical Association Helsinki Declaration revised in 2013,and informed consent for clinical research was signed with the children′s guardians.Results①Based on results of combined laboratory diagnosis and/or genetic diagnosis,124 newborns with G6PD deficiency were finally diagnosed(121 cases were diagnosed by G6PD enzyme activity test,113 cases were diagnosed by G6PD gene mutation detection,and 110 cases were diagnosed by these two methods).②Among the 121 children diagnosed as G6PD deficiency by G6PD enzyme activi

关 键 词：葡糖磷酸脱氢酶缺乏 新生儿筛查 葡萄糖-6-磷酸脱氢酶缺乏症 聚合酶链反应 荧光定量PCR法 荧光PCR熔解曲线法 地域性分布 婴儿 新生 

分 类 号：R722.1[医药卫生—儿科]