福建泉州地区新生儿戊二酸血症Ⅱ型患者的实验室筛查和基因诊断分析  

Laboratory Screening and Genetic Diagnosis Analysis of Patients with Neonatal Glutaric Acidemia Type II in Quanzhou,Fujian Province

作　　者：林春妹 彭维林 林壹明 LIN Chunmei;PENG Weilin;LIN Yiming(Department of Clinical Laboratory,Quanzhou Wonen’s and Children’s Hospital,Fujina Quanzhou 362000,China)

机构地区：[1]泉州市妇幼保健院/儿童医院检验科,福建泉州362000

出　　处：《现代检验医学杂志》2024年第6期185-188,228,共5页Journal of Modern Laboratory Medicine

基　　金：华侨大学附属妇儿医院院校联合创新项目(2021YX003)。

摘　　要：目的了解福建省泉州地区戊二酸血症Ⅱ型(glutaric acidemia typeⅡ,GA-Ⅱ)新生儿发病率、生化表现与基因突变特征。方法2014年1月~2022年12月,采用串联质谱技术对泉州地区643606例新生儿进行遗传代谢病筛查。对于多种酰基肉碱升高的可疑阳性样本采用MassARRAY技术和高通量测序技术诊断。结果研究期间共有247例新生儿表现为多种酰基肉碱升高,经过基因诊断确诊19例GA-Ⅱ患儿。此外,1例新生儿表现为异戊酰基肉碱(isovalerylcarnitine,C5)升高,疑似为异戊酸血症,经过基因诊断证实为GA-Ⅱ。该研究最终确诊20例GA-Ⅱ患儿,GA-Ⅱ在研究人群中的发病率为1∶32180。新生儿筛查结果表明辛酰基肉碱(C8),癸酰基肉碱(C10)和十二烷酰基肉碱(C12)的浓度明显高于参考范围上限,是筛查GA-Ⅱ的关键指标。在GA-Ⅱ患儿中发现了10种不同的电子转移黄素蛋白脱氢酶(electrontransfer flavoprotein dehydrogenase,ETFDH)基因突变,大部分为错义突变。最常见的ETFDH基因突变是c.250G>A(p.A84T),等位基因突变频率达47.5%,其次是c.524G>A(R175H),c.998A>G(p.Y333C)和c.1657T>C(p.Y553H)。结论新生儿筛查是早期检出GA-Ⅱ患儿的重要途径,但GA-Ⅱ患儿可能出现非典型性的生化改变,所有新生儿筛查结果异常的样本应采用高通量测序进行基因诊断。Objective To investigate the incidence,biochemical manifestations and genetic mutation features of glutaric acidemia type II(GA-II)in newborns in Quanzhou,Fujian province.Methods From January 2014 to December 2022,a total of 643606 newborns were screened for inherited metabolic diseases by tandem mass spectrometry in the Quanzhou area.Suspected positive newborns with multiple acylcarnitine elevations were diagnosed by the MassARRAY assay and high-throughput sequencing technology.Results A total of 247 newborns showed multiple acylcarnitine elevations during the study period,and 19 newborns were diagnosed with GA-II by genetic diagnosis.In addition,one newborn showed elevated levels of isovalerylcarnitine(C5),and was suspected to be isovaleric acidemia,which was confirmed with GA-II by genetic diagnosis.Twenty newborns were eventually diagnosed with GA-II,and the incidence of GA-II in the study population was 1∶32180.Newborn screening results showed the concentrations of octanoylcarnitine(C8),decanoylcarnitine(C10)and dodecanylcarnitine(C12)were higher than the upper limit of the reference range,which were key indicators for screening GA-II.Ten distinct electrontransferflavoprotein dehydrogenase ETFDH gene mutations were found in patients with GA-II,most of which were missense mutations.The most common ETFDH mutation was C.250G>A(p.A84T)with an allele frequency of 47.5%,followed by C.524G>A(R175H),C.998A>G(p.Y333C)and C.1657T>C(p.Y553H).Conclusion Newborn screening is an important approach for early detection of GA-II,but patients with GA-II may have atypical biochemical changes,and all newborns with abnormal newborn screening results should be subjected to high-throughput sequencing for genetic diagnosis.

关 键 词：戊二酸血症Ⅱ型 新生儿筛查 串联质谱技术 电子转移黄素蛋白脱氢酶基因 

分 类 号：R722.11[医药卫生—儿科] Q754[医药卫生—临床医学]