摘要
目的探究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效果。方法回顾性分析2016年6月至2020年6月深圳市儿童医院收治的临床表现疑似遗传代谢病高危新生儿289例为研究对象,所有患儿均给予质谱检测联合下一代测序筛查遗传代谢病,随访至6个月龄结局。结果以下一代测序检测为金标准,289例疑似遗传代谢病新生儿中,最终确诊病例为40例,其中男性22例,女性18例;脂肪酸代谢病15例,氨基酸代谢病14例,有机酸代谢病11例。质谱检测提示遗传代谢疾病为34例,质谱检测的敏感度78.8%(95%CI:61.1%~91.0%),特异度100%(95%CI:99.8%~100%),阳性预测值100%,阴性预测值为99.7%(95%CI:99.3%~99.8%)。质谱检测与下一代测序检测提示遗传代谢病可能结果不一致者有2例,质谱检测1例检测到丙氨酸或酪氨酸代谢异常,但下一代测序基因存在3-甲基戊烯二酸尿症;1例质谱检测血酪氨酸异常升高,但下一代测序中存在基因半合变异,诊断为3-甲基巴豆酰辅酶A羧化酶乏症。40例患儿经随访其中1例甲基丙二酸血症患儿出现急性代谢紊乱,家属放弃治疗死亡,其余患儿基于明确的诊断,干预及时,生长发育良好。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,质谱检测联合下一代测序可以更加快速且全面确诊临床表现疑似遗传代谢病的高危新生儿,尽早实施个体化治疗,改善患儿预后。
Objective To explore the application effect of mass spectrometry combined with next-generation sequencing in the diagnosis of neonatal genetic and metabolic diseases.Methods A retrospective analysis was performed on 289 high-risk newborns with suspected clinical manifestations of genetic metabolic diseases admitted to Shenzhen Children’s Hospital from June 2016 to June 2020.All children were given mass spectrometry combined with next-generation sequencing to screen for genetic metabolic diseases,and they were followed up till 6 months-old.Results With next-generation sequencing as the gold standard,among 289 neonates with suspected genetic metabolic diseases,40 were finally confirmed,including 22 males and 18 females;there were 15 neonates with fatty acid metabolism diseases,14 neonates with amino acid metabolism diseases,and 11 neonates with organic acid metabolism diseases.Mass spectrometry detection revealed 34 cases of genetic and metabolic diseases,with the sensitivity of 78.8%(95%CI:61.1%to 91.0%),the specificity of 100%(95%CI:99.8%to 100%),the positive predictive value of 100%,and the negative predictive value of 99.7%(95%CI:99.3%to 99.8%).Mass spectrometry detection and next-generation sequencing detection showed inconsistent results in 2 cases,of which 1 case was detected as abnormal metabolism of alanine or tyrosine by mass spectrometry but as 3-methylglutaconic aciduria by the next-generation sequencing,the other case as abnormally elevation of blood tyrosine by mass spectrometry but as gene hemizygous mutations by next-generation sequencing(diagnosed as 3-methylcrotonyl-CoA carboxylase deficiency).During the follow-up,among the 40 children,1 child with methylmalonic acidemia developed acute metabolic disorders and then died after giving up treatment,and the rest received timely intervention based on diagnosis and developed well.Conclusion Mass spectrometry can diagnose genetic and metabolic diseases relatively quickly to guide clinical treatment,while next-generation sequencing can verify the result
作者
于爱真
冯雪
王欣
YU Ai-zhen;FENG Xue;WANG Xin(Department of Pediatrics,Shenzhen Children's Hospital,Shenzhen 518000,Guangdong,CHINA)
出处
《海南医学》
CAS
2021年第2期177-180,共4页
Hainan Medical Journal
基金
广东省深圳市知识创新计划基础研究项目(编号:201884445)。
关键词
质谱检测
遗传代谢病
下一代测序
新生儿
基因
Mass spectrometry
Genetic metabolic diseases
Next-generation sequencing
Newborns
Genes
