串联质谱技术联合高通量测序技术在聊城地区22457例新生儿遗传代谢病筛查中的应用价值

Application value of tandem mass spectrometry combined with high-throughput sequencing in screening of inherited metabolic diseases in 22457 neonates in Liaocheng region

目的探讨在新生儿遗传代谢病的筛查过程中串联质谱技术联合高通量测序技术的临床应用价值,初步分析聊城地区新生儿遗传代谢病的发病情况。方法选取2020年1月—2021年8月在聊城市东昌府区妇幼保健院进行遗传代谢病检测的22457例新生儿足跟血标本,采用串联质谱技术进行遗传代谢病筛查,对复筛阳性样本通过高通量测序技术进行新生儿常见遗传病基因检测,并对检测结果进行统计分析。结果共筛查新生儿22457例,其中初筛阳性552例(2.46%),复筛阳性146例(0.65%),总阳性预测值为1.56%。对复筛阳性患儿进行高通量测序,共检出遗传代谢病相关突变基因13个,突变位点78个,包括18个致病位点、16个疑似致病位点及44个意义未明位点,其中纯合突变3例,复合杂合突变13例,杂合突变76例,涉及10种遗传代谢病,最终确诊遗传代谢病8例,发病率为1/2807,其中3-甲基巴豆酰辅酶A羧化酶缺乏症2例,甲基丙二酸血症2例,苯丙酮尿症3例,短链酰基辅酶A脱氢酶缺乏症1例。结论串联质谱技术是遗传代谢病快速有效的筛查方法,高通量测序技术则进一步提供了明确的分子诊断,串联质谱技术联合高通量测序技术可为遗传代谢病的早期诊断和治疗提供依据。

Objective To explore the clinical application value of tandem mass spectrometry combined with high-throughput sequencing in screening of inherited metabolic diseases,preliminarily analyze the incidence rate of neonatal inherited metabolic diseases in Liaocheng region.Methods Heel blood samples from 22457 neonates tested for inherited metabolic diseases in Maternal and Child Health Hospital of Dongchangfu District from January 2020 to August 2021 were selected.Tandem mass spectrometry was used to screen for inherited metabolic diseases.The positive samples were screened for common inherited metabolic diseases of neonates by high-throughput sequencing,and the test results were statistically analyzed.Results A total of 22457 neonates were screened,of which 552 cases(2.46%)were positive during primary screening and 146 cases(0.65%)were positive during secondary screening.The total positive predictive value was 1.56%.A total of 13 mutant genes related to inherited metabolic diseases and 78 mutant sites were detected by high-throughput sequencing,including 18 pathogenic sites,16 suspected pathogenic sites,and 44 sites of unknown significance.There were 3 homozygous mutations,13 complex heterozygous mutations,and 76 heterozygous mutations,involving 10 kinds of inherited metabolic diseases.Finally,8 cases of inherited metabolic diseases were confirmed with an incidence rate of 1/2807,including 2 cases of 3-methylcrotonyl coA carboxylase deficiency,2 cases of methylmalonic acidemia,3 cases of phenylketonuria,and 1 case of short chain acyl-coA dehydrogenase deficiency.Conclusion Tandem mass spectrometry is a rapid and effective screening method for inherited metabolic diseases,and high-throughput sequencing further provides a clear molecular diagnosis.The combined detection of tandem mass spectrometry and high-throughput sequencing is beneficial to the early diagnosis and treatment of inherited metabolic diseases.