徐州地区尿素循环障碍类疾病的新生儿串联质谱筛查及基因变异分析  

Tandem mass spectrometry screening and genetic analysis of neonates with Urea cycle disorders in Xuzhou region

作　　者：周伟 李惠中 杨丽 邵芳[1] 顾茂胜 Zhou Wei;Li Huizhong;Yang Li;Shao Fang;Gu Maosheng(Department of Medical Genetics and Prenatal Diagnosis,Xuzhou Maternity and Child Health Care Hospital,Xuzhou,Jiangsu 221009,China)

机构地区：[1]徐州市妇幼保健院医学遗传与产前诊断科,徐州221009

出　　处：《中华医学遗传学杂志》2025年第1期26-33,共8页Chinese Journal of Medical Genetics

基　　金：徐州市卫生健康委员会医学青年后备人才培养项目(XWRCHT20220003)。

摘　　要：目的探讨徐州地区4种尿素循环障碍类疾病(UCDs)新生儿串联质谱筛查结果和基因变异特征。方法选择2015年11月至2023年12月于徐州市妇幼保健院新生儿疾病筛查中心进行遗传代谢病串联质谱筛查的691712例新生儿,经血氨基酸串联质谱法、基因检测,最终将确诊为鸟氨酸氨甲酰转移酶缺乏症(OTCD)、氨甲酰磷酸合酶1缺乏症(CPS1D)、精氨酸酶缺乏症(ARGD)、精氨酰琥珀酸合成酶缺乏症(ASSD)的10例患儿(患儿1~10)作为研究对象。采用回顾性研究方法,收集所有患儿血氨基酸串联质谱筛查结果、基因检测结果,并对基因变异位点进行生物信息学分析。本研究通过了徐州市妇幼保健院医学伦理委员会的审查(批准号:XZFY2024-051K-01J)。结果本研究691712例新生儿中,血氨基酸串联质谱筛查结果显示,OTCD、CPS1D、ASSD、ARGD初筛阳性数分别为1237、1237、510、1009例,经基因检测,被确诊为OTCD、CPS1D、ASSD、ARGD者分别为1、1、1、7例。血氨基酸串联质谱筛查这4种UCDs的总阳性预测值为0.362%。10例UCDs患儿中,基因测序检出4种新变异:OTC基因c.1024C>A(p.L342M),ASS1基因c.826A>G(p.M276V)、c.695C>T(p.P232L)和c.694C>T(p.P232S)。对这4种变异进行生物信息学分析结果显示,根据美国医学遗传学与基因组学学会(ACMG)制定的《遗传变异分类标准与指南》,这4种新变异被评为临床意义未明变异、疑似致病性变异。结论徐州地区4种UDCs新生儿患病率较低,基因突变型与临床表型存在一定关联。针对临床意义不明和疑似致病性的新变异,应结合临床和生化指标等明确变异的致病性。该研究发现的4种UCDs致病基因新变异类型丰富了徐州地区UCDs相关的致病基因变异谱。ObjectiveTo explore the results of four types of Urea cycle disorders(UCDs)in newborns from the Xuzhou region,assess the efficacy of newborn screening by tandem mass spectrometry(MS/MS),and analyze their genetic characteristics.MethodsA retrospective analysis was performed using tandem mass spectrometry to screen for inherited metabolic disorders in 691712 newborns at the Maternal and Child Health Care Hospital of Xuzhou from November 2015 to December 2023.Ten children(cases 1-10)were diagnosed with Ornithine transcarbamylase deficiency(OTCD),Carbamoylphosphate synthase 1 deficiency(CPS1D),Arginase deficiency(ARGD),and Argininosuccinate synthase deficiency(ASSD)based on MS/MS and genetic testing.This study was approved by the Medical Ethics Committee of Xuzhou Maternity and Child Health Care Hospital(Ethics No.XZFY2024-051K-01J).ResultsA total of 691712 neonates were screened for UCDs using MS/MS,which identified 1237,1237,510,and 1009 initial positive cases for OTCD,CPS1D,ASSD,and ARGD,respectively.After genetic testing,1 case of OTCD,1 case of CPS1D,1 case of ASSD,and 7 cases of ARGD were confirmed.The overall positive predictive value for these four UCDs was 0.362%.Among the 10 diagnosed UCD cases,four novel variants were identified,which included OTC:c.1024C>A(p.L342M)and ASS1:c.826A>G(p.M276V),c.695C>T(p.P232L)and c.694C>T(p.P232S).Bioinformatic analysis has rated these as variants of uncertain clinical significance or likely pathogenic based on guidelines from the American College of Medical Genetics and Genomics(ACMG).ConclusionThe incidence of four UCDs in neonates from the Xuzhou area is relatively low,and there is a correlation between genetic variants and clinical phenotypes.For novel variants with uncertain clinical significance or suspected pathogenicity,their pathogenicity should be clarified in conjunction with clinical and biochemical indicators.The four novel pathogenic variants of UCDs identified in this study have enriched the mutational spectrum of UCDs-associated genes in the Xuzhou region.

关 键 词：尿素循环障碍 先天性 基因变异 串联质谱法 新生儿筛查 鸟氨酸氨甲酰转移酶缺乏症 氨甲酰磷酸合酶Ⅰ缺乏病 高精氨酸血症 新生儿 

分 类 号：R72[医药卫生—儿科]