串联质谱联合二代测序在2万例新生儿遗传病筛查分析中的应用

Application of tandem mass spectrometry combined with second-generation sequencing in the screening and analysis of 20 000 cases of neonatal genetic diseases

目的研究新生儿遗传代谢病(IMD)的发病率及诊断方法,并探讨串联质谱及二代测序技术在新生儿遗传病筛查中的应用价值。方法收集广东地区2013年6月至2019年6月出生的20000例新生儿足跟血,采用串联质谱(MS/MS)进行检测并进行遗传代谢病分析,对质谱检测结果高度提示阳性及部分疑似样本进行基因测序分析,并对检测结果进行统计分析。结果20000例新生儿(男10584例,女9416例)中通过MS/MS技术诊断IMD阳性40例,疑似样本45例,阴性样本19915例(其中24例临床高度怀疑IMD),进而对质谱检测阳性、疑似及临床高度怀疑IMD的109例样本进行基因测序分析,共检测出阳性病种17种共63例,阳性率0.315%,分别为有机酸血症25例,尿素循环障碍22例,氨基酸代谢病6例,脂肪酸氧化障碍4例,肝豆状核变性3例,葡萄糖-6-磷酸脱氢酶缺乏症2例,半乳糖血症1例。结论MS/MS是新生儿IMD快速有效的筛查方法,而二代测序则提供了明确的分子诊断,因此,基于MS/MS及二代测序技术可为新生儿IMD早期诊断和治疗提供依据。

Objective To study the incidence and diagnostic methods of neonatal inherited metabolic disease(IMD),and to explore the application value of tandem mass spectrometry and second-generation sequencing technology in the screening of neonatal genetic diseases.Methods The heel blood of 20000 newborns born between June 2013 and June 2019 in Guangdong area was collected.Tandem mass spectrometry(MS/MS)was used to detect and analyze genetic and metabolic diseases.The results of mass spectrometry were highly suggestive of positive and partial suspected samples are analyzed by gene sequencing,and the test results were statistically analyzed.Results Among 20000 newborns(10584 males and 9416 females),40 cases were diagnosed as positive for IMD,45 cases for suspected samples,and 19915 cases for negative samples(24 cases of clinically highly suspected IMD)were diagnosed by MS/MS technology.Gene sequencing analysis was performed on 109 samples of positive,suspected and highly clinically suspected IMD.A total of 63 cases were detected with 17 positive diseases,with a positive rate of 0.315%,including 25 cases of organic acidemia and 22 cases of urea cycle disorders.There were 6 cases of amino acid metabolism disease,4 cases of fatty acid oxidation disorder,3 cases of hepatolenticular degeneration,2 cases of glucose-6-phosphate dehydrogenase deficiency,and 1 case of galactosemia.Conclusions MS/MS is a fast and effective screening method for neonatal IMD,while genetic testing provides a clear molecular diagnosis.Therefore,based on MS/MS and genetic analysis technology can provide evidence for early diagnosis and treatment of neonatal IMD.