生化与热点基因筛查新生儿遗传代谢病的多中心研究

A multi-center study of biochemical and hotspot gene screening for neonatal genetic metabolic diseases

目的探讨新生儿遗传代谢病生化和热点基因筛查的检测效率。方法本研究为前瞻性多中心研究。对来自10个省区12家医院的2020年11月至2021年11月出生的21442例新生儿样本进行生化和热点基因联合筛查。生化筛查包含葡萄糖-6-磷酸脱氢酶缺乏症酶活性检测及新生儿串联质谱筛查。基因筛查包括75种新生儿疾病相关的135个基因。结果收集到各地区生化筛查结果的新生儿数目为21205例,初筛阳性813例,经召回复查累计确诊95例(0.45%)。纳入研究的新生儿样本均进行基因筛查总计21442例,初筛阳性168例,确诊156例(0.73%)。生化结合基因筛查可提高包括原发性肉碱缺乏症、新生儿肝内胆汁淤积症及2-甲基丁酰甘氨酸血症等疾病的检出敏感性,并扩大筛查范围,将较为常见的单基因遗传病,如珠蛋白生成障碍性贫血及肝豆状核变性等疾病纳入检测范围。结论在新生儿筛查中,联合使用生化筛查和基因筛查可以扩大筛查范围,提高筛查效率。

Objective To investigate the efficiency of biochemical screening and hotspot gene screening in the detection of neonatal inherited metabolic diseases.Methods This was a prospective multi-center study.The study was carried out on 21442 neonatal samples collected from 12 hospitals in 10 provinces from November 2020 to November 2021.The results of biochemical screening and hotspot gene screening were analyzed jointly.Biochemical screening methods included glucose-6-phosphate dehydrogenase deficiency enzyme activity assay and neonatal tandem mass spectrometry.Genetic screening analysis involved 135 genes associated with 75 neonatal diseases.Results Of all the 21442 neonates enrolled in the study,21205 were subject to biochemical screening.A total of 813 cases were positive in the initial screening,and 0.45%of them(95 cases)were diagnosed after recall.All the 21442 neonates underwent gene screening.About 168 positive cases were detected in the initial screening,and 0.73%(156 cases)of them were confirmed finally.Biochemical and genetic screening improved the detection sensitivity of such diseases as primary carnitine deficiency,neonatal intrahepatic cholestasis caused by citrin deficiency,and 2-methylbutyrylglycinemia.Moreover,biochemical and genetic screening enabled the detection of more diseases,including the common single-gene genetic diseases such as thalassemia and Wilson disease.Conclusions In neonatal screening,the combination of biochemical screening and gene screening expands the number of diseases detected and improve screening efficiency.