串联质谱联合高通量测序技术在新生儿遗传代谢病(IEM)筛查诊断中的应用价值

Application value of tandem mass spectrometry combined with high-throughput sequencing technology in the screening and diagnosis of neonatal genetic metabolic disease(IEM)

目的:探讨串联质谱联合高通量测序技术在新生儿遗传代谢病(IEM)筛查诊断中的应用价值。方法:回顾性分析本院2023年1月至2023年10月接收的3625例接受IEM筛查的新生儿的临床资料,对IEM患儿与正常新生儿的基本资料进行比较,并分析IEM新生儿的变异情况。结果:本组新生儿中基因变异共15例;IEM患儿与正常新生儿的基本资料差异无统计学意义(P>0.05);IEM相关基因变异的15例新生儿中,ACAD8基因复合杂合变异1例,SLC22A5基因变异携带者1例,前者被诊断为异丁酰辅酶A脱氢酶缺乏症,后者被诊断为原发性肉碱缺乏症;3例SLC22A5变异新生儿的游离肉碱水平(7.80±1.26)μmol/L明显低于3622例SLC22A5未变异新生儿的游离肉碱水平(18.95±3.25)μmol/L(P<0.05);4例MCC1/MCC2变异新生儿的丁二酰肉碱+3-羟基异戊酰基碱水平(0.48±0.08)μmol/L明显高于3621例MCC1/MCC2无变异新生儿的丁二酰肉碱+3-羟基异戊酰基碱水平(0.17±0.03)μmol/L(P<0.05)。结论:新生儿IEM筛查诊断中串联质谱联合高通量测序技术可取得确切的应用效果,对于存在基因变异携带的患者,要与其临床症状结合来开展诊断工作,避免出现漏诊的情况。

Objective:To explore the application value of tandem mass spectrometry combined with high-throughput sequencing technology in the screening and diagnosis of neonatal genetic metabolic disease(IEM).Methods:Clinical data on 3,625 newbo-rns screened by IEM received by our hospital from January 2023 to October 2023 were retrospectively analyzed,basic data on IEM patients and normal newborns were compared,and the variation of IEM newborns was analyzed.Results:There were 15 cases of genetic variants in this group of newborns;the difference in basic data between IEM patients and normal newborns was not statistically significant(P>0.05);among 15 newborns with IEM-related gene variants,1 case of ACAD8 gene complex hybrid variant and 1 SLC22A5 gene mutation carrier.The former was diagnosed as isobutyl-CoA dehydrogenase deficiency;the latter was diagnosed as primary carnitine deficiency;The level of free carnitine in 3 neonates with SLC22A5 mutation(7.80±1.26)μmol/L was significantly lower than that in 3622 neonates without SLC22A5 mutation(18.95±3.25)μmol/L(P<0.05);Levels of succinyl carnitine+3-hydroxyisovaleryl base in 4 neonates with MCC1/MCC2 variant(0.48±0.08)μmol/L was significantly higher than the level of succinyl carnitine+3-hydroxyisovaleryl base(0.17±0.03)μmol/L in 3621 neonates without MCC1/MCC2 variation(P<0.05).Conclusion:Tandem mass spectrometry combined with high-throughput sequen-cing technology can achieve accurate application results in neonatal IEM screening and diagnosis.For patients carrying genetic mutations,diagnosis work should be carried out in combination with their clinical symptoms to avoid missed diagnosis.