质谱检测联合下一代测序在新生儿遗传代谢病诊断中的应用  

Application of mass spectrometry combined with next generation sequencing in the diagnosis of neonatal inherited metabolic diseases

作　　者：蒋文星[1] 陈丽萍[1] 李红[2] 郭智彬[2] 袁意[3] 周斌[3] 卢文青[1] 杨琳[4] 吴冰冰[4] 周敏丽 Jiang Wenxing;Chen Liping;Li Hong;Guo Zhibin;Yuan Yi;Zhou bin;Lu Wenqing;Yang Lin;Wu Bingbing;Zhou Minli(Department of Neonatology,Jiangxi Provincial Children′s Hospital,Nanchang 330006,China;Department of Central Laboratory,Jiangxi Provincial Children′s Hospital,Nanchang 330006,China;Department of Endocrinology,Metabolism and Genetics,Jiangxi Provincial Children′s Hospital,Nanchang 330006,China;Shanghai Key Laboratory of Birth Defects,the Translational Medicine Center of Children Development and Disease of Fudan University,Children′s Hospital of Fudan University,Shanghai 201102,China)

机构地区：[1]江西省儿童医院新生儿科,南昌330006 [2]江西省儿童医院中心实验室,南昌330006 [3]江西省儿童医院内分泌遗传代谢科,南昌330006 [4]上海市出生缺陷防治重点实验室复旦大学附属儿科医院儿童发育与疾病转化医学研究中心,上海201102

出　　处：《中华医学杂志》2020年第21期1640-1647,共8页National Medical Journal of China

基　　金：江西省卫生健康委员会科技计划项目(20195552);江西省自然科学基金(20171BAB205043)。

摘　　要：目的评估质谱检测联合下一代测序在新生儿遗传代谢病诊断中的应用价值。方法回顾性分析江西省儿童医院新生儿科2017年3月至2019年9月收治的19例遗传代谢病新生儿的临床信息、血尿代谢产物检测及基因检测结果。血尿代谢产物分别通过液相色谱-串联质谱及气相色谱-质谱技术检测,全血样本采用基于下一代测序的新生儿遗传病基因panel检测。结果19例患儿中,有12例患儿的代谢产物质谱检测结果与基因检测结果一致;2例患儿的质谱检测结果与基因检测结果不一致;4例质谱检测未提示病种,经过基因检测得出与患儿临床表型部分相符的疾病诊断;1例未行质谱检测的患儿,因基因检测而考虑遗传代谢病诊断,并以此为依据进行随诊。结论质谱检测可以相对快速诊断遗传代谢病以指导临床治疗,而下一代测序可对质谱检测结果进行验证,并从基因角度解释病因,从而指导进一步治疗及遗传咨询。Objective To explore the application value of mass spectrometry(MS)combined with next generation sequencing(NGS)in diagnosing neonatal inherited metabolic diseases(IMD).Methods The clinical information,metabolites in blood and urine,and gene sequencing results of 19 neonates with IMD coming from the Department of Neonatology of Jiangxi Provincial Children′s Hospital from March 2017 to September 2019 were analyzed retrospectively.The metabolites in blood were detected by liquid chromatography tandem mass spectrometry and urine were detected by gas chromatography-mass spectrometry respectively.Meanwhile,the whole bloods were dectected by neonatal genetic disease panel based on NGS.Results Twelve neonates had the same results between MS and NGS among the 19,2 had different results from MS to NGS,and 4 had no disease indication by MS but were diagnosed by NGS whose clinical phenotype were partially consistent with NGS results.One of them who did not carry out MS was considered as the diagnosis of IMD because of the detection of gene,and was followed up on this basis.Conclusion MS could diagnose IMD relatively quickly to guide clinical treatment,and while NGS could verify the results of MS detection.Combination of MS and NGS would understand the cause of disease on genetic level,so as to guide further treatment and genetic consultation.

关 键 词：代谢疾病 串联质谱法 基因测定 新生 

分 类 号：R722[医药卫生—儿科]