长沙地区352449例新生儿多种遗传代谢病的筛查结果分析

Analysis of screening results for genetic metabolic diseases among 352449 newborns from Changsha

目的回顾性分析长沙地区新生儿多种遗传代谢病的筛查情况,了解其单病种患病率及基因变异情况。方法对长沙地区2016年1月至2021年12月出生的352449例新生儿进行串联质谱筛查,对筛查阳性者进一步行生化检测和基因变异分析以确诊。结果新生儿中初筛阳性6170例,阳性率1.75%;召回5437例,确诊92例,总体患病率为1/3831,阳性预测值为1.69%。92例患儿共计检出18种遗传代谢病,包括氨基酸代谢病33例,其中苯丙氨酸羟化酶缺乏症20例,占60.60%;有机酸代谢病17例,其中2-甲基丁酰辅酶A脱氢酶缺乏症4例,占23.50%;脂肪酸代谢病42例,其中原发性肉碱缺乏症27例,占64.30%,短链酰基辅酶A脱氢酶缺乏症12例,占28.60%。基因分析共发现90种基因变异,最常见者为c.51C>G、c.1400C>G、c.760C>T、c.1031A>G和c.1165A>G。结论长沙地区新生儿遗传代谢病患病率较高者为原发性肉碱缺乏症、苯丙氨酸羟化酶缺乏症和短链酰基辅酶A脱氢酶缺乏症。本研究初步阐明了长沙地区遗传代谢病患儿的基因变异谱,有助于实现早期诊断及干预,提高出生人口的素质。

Objective To retrospectively analyze the screening results for genetic metabolic diseases among newborns from Changsha in order to determine the prevalence of single diseases and their mutational spectrum.Methods 352449 neonates born from January 2016 to December 2021 in Changsha were subjected to tandem mass spectrometry.Suspected cases were further analyzed by biochemical and genetic testing.Results Among the 352449 newborns,6170 were positive for the screening,which yielded a positive rate of 1.75%.5437 cases were recalled,and 92 were confirmed,with the overall prevalence being 1∶3831 and positive predictive value of 1.69%.Eighteen genetic metabolic diseases were detected among the 92 children,including 33 amino acid metabolic disorder,among which 20 were phenylalanine hydroxylase deficiency(60.60%).17 cases had organic acid metabolic disorders,among which 4 were 2-methyl-dehydrogenase deficiency(23.50%).42 had fatty acid metabolic disorders,among which 27(64.30%)were primary carnitine deficiency and 12 were short-chain acyl-CoA dehydrogenase deficiency(28.60%).In total 90 genetic variants were identified,with the most common ones including c.51C>G,c.1400C>G,c.760C>T,c.1031A>G and c.1165A>G.Conclusion The common neonatal genetic metabolic diseases in Changsha include primary carnitine deficiency,phenylalanine hydroxylase deficiency and short-chain acyl-CoA dehydrogenase deficiency.The preliminary delineation of mutational spectrum for genetic metabolic diseases in Changsha can facilitate early diagnosis and intervention,so as to improve the quality of newborn population.