济宁地区新生儿遗传代谢病串联质谱筛查结果分析

Analysis of tandem mass spectrometry screening results of neonatal genetic metabolic diseases in Jining city

目的:了解济宁地区遗传代谢病的患病率、疾病构成和基因变异类型。方法:采集2022年1月-12月参加新生儿疾病筛查的新生儿足跟血,用串联质谱(tandemmassspectrometry,MS/MS)法检测血中氨基酸、肉碱和琥珀酸丙酮浓度,筛查遗传代谢病。用核酸质谱和二代测序检测突变基因,Sanger测序验证,用百分位数法确定参考值范围。结果:52192例新生儿遗传代谢病MS/MS初次筛查阳性1298例,召回1188例,阳性召回率91.53%(1188/1298)。确诊遗传代谢病32例,阳性预测值2.69%(32/1188),总患病率为1/1631。以氨基酸代谢疾病最常见,占56.25%(18/32),其次为有机酸代谢疾病和脂肪酸氧化代谢疾病,分别占28.13%(9/32)和15.63%(5/32)。常见的突变基因是PAH和MAT1A,有机酸代谢疾病常见的突变基因为MMACHC,脂肪酸氧化代谢疾病常见的突变基因为ACADVL。结论:氨基酸代谢疾病是济宁地区新生儿最常见的遗传代谢病,其常见突变基因为PAH和MAT1A。建立遗传代谢病MS/MS筛查切值,探讨疾病构成及其热点突变基因位点,有助于遗传代谢病的早期诊断和精准治疗。

Objective:To understand the prevalence,disease composition and genetic variant type of genetic metabolic diseases in Jining region.Methods:The heel blood of newborns attending neonatal disease screening from January to December 2022 was collected,and the blood concentrations of amino acid,carnitine and acetone succinate were detected by tandem mass spectrometry(tandem mass spectrometry,M S/MS)to screen for genetic metabolic diseases.Mutated genes were detected by nucleic acid mass spectrometry and second-generation sequencing and verified by Sanger sequencing,and reference ranges were determined by the percentile method.Results:52,192 neonatal M S/MS were positive,1188 were recalled,with a positive recall rate of 91.53%(1188/1298).32 cases of genetic metabolic diseases were confirmed,with a positive predictive value of 2.69%(32/1188),and an overall prevalence was 1/1631.Amino acid metabolism diseases were the most common,accounting for 56.25%(18/32),followed by organic acid metabolism diseases and fatty acid oxidation metabolism diseases,accounting for 28.13%(9/32)and 15.63%(5/32),respectively.The common mutated genes were PAH and MAT1A,the common mutated genes for organic acid metabolic diseases were MMACHC,and the commonly mutated genes for fatty acid oxidative metabolic diseases were ACADVL.Conclusion:Amino acid metabolic diseases are the most common genetic metabolic diseases in newborns in Jining region,and their mutation genes are PAH and MAT1A.The screening value of M S/MS of genetic metabolic diseases is established to explore the disease composition and its hot spot mutation gene locus,which is helpful to the early diagnosis and precise treatment of genetic metabolic diseases.