背景:先天性代谢错误(IEM)的发生率因国家和地区而异。目前,在中国东部沿海地区,没有使用新生儿筛查(NBS)进行IEM的研究。我们旨在估计IEM的发病率和遗传变异,并了解IEM引起的疾病谱及其变异。
方法:回顾性回顾了2016年至2021年通过串联质谱(MS/MS)进行的NBS。在出生后72小时从所有新生儿收集脚跟血。进行靶向大规模平行测序用于遗传分析。
结果:在245,194名新生儿中,95人被诊断为IEM,观察到的总发病率为-IEM:1/2581;氨基酸代谢紊乱:1/4715;有机酸代谢紊乱:1/11676;脂肪酸代谢紊乱:1/11145.不同IEM的发生率在1/245194至1/6452的范围内。苯丙酮尿症(PKU,1/7211)是最常见的IEM,其次是甲基丙二酸血症(MMA,1/27244),短链酰基辅酶A脱氢酶缺乏症(SCADD,1/30649),和citrin缺乏症(CD,1/35028)。对于遗传变异,发现的常见热点变异是PKU的PAH基因:c.728G>A,c.442-1G>A,c.611A>G,c.721C>T;非经典PKU的PTS基因:c.259C>T;MMACHC基因为MMA:c.658_660delAAG,c.609G>A;MMA的MMUT基因:c.1663G>A;SCADD的ACADS基因:c.1031A>G和c.1130C>T;CD的SLC25A13基因:c.1638_1660dup,c.852_855del。
结论:本研究显示了中国东部沿海地区IEM的疾病和不同范围。通过MS/MS结合大规模并行测序实施用于IEM的NBS可以为NBS检测IEM提供改进的计划。
The incidence of inborn errors of metabolism (IEM) varies across countries and areas. Currently, there are no studies on IEM using newborn screening (
NBS) in eastern coastal areas of
China. We aimed to estimate the incidence and genetic variants of IEM and understand the spectrum of diseases caused by IEM and variants among them in this area.
The
NBS performed by tandem mass spectrometry (MS/MS) from 2016 to 2021 was retrospectively reviewed. Heel blood was collected from all newborns 72 h after birth. Targeted massively parallel sequencing was performed for genetic analysis.
Among 245,194 newborns, 95 were diagnosed with IEM, the overall incidence observed was-IEM: 1/2581; amino acid metabolism disorder: 1/4715; organic acid metabolism disorder: 1/11676; and fatty acid metabolism disorder: 1/11145. The incidence of different IEM was in the range of 1/245194 to 1/6452. Phenylketonuria (PKU, 1/7211) was the most common IEM, followed by methylmalonic acidemia (MMA, 1/27244), short-chain acyl-CoA dehydrogenase deficiency (SCADD, 1/30649), and citrin deficiency (CD, 1/35028). For genetic variants, the common hotspot variants found were-PAH gene for PKU: c.728G > A, c.442-1G > A, c.611A > G, c.721C > T; PTS gene for non-classical PKU: c.259C > T; MMACHC gene for MMA: c.658_660delAAG, c.609G > A; MMUT gene for MMA: c.1663G > A; ACADS gene for SCADD: c.1031A > G and c.1130C > T; and SLC25A13 gene for CD: c.1638_1660dup, c.852_855del.
This study displayed the diseases and varied spectrum of IEM in eastern coastal areas of
China. Implementing
NBS for IEM by MS/MS combined with massively parallel sequencing can offer an improved plan for
NBS to detect IEM.