Department of Prenatal Diagnosis, Lianyungang Maternal and Child Health Hospital, Lianyungang, Jiangsu, People's Republic of China.
Mol Genet Genomic Med. 2023 Jun;11(6):e2152. doi: 10.1002/mgg3.2152. Epub 2023 Feb 14.
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.
先天性代谢缺陷（IEM）的发病率在不同国家和地区有所不同。目前，中国东部沿海地区尚未有使用新生儿筛查（NBS）进行 IEM 的研究。本研究旨在评估该地区 IEM 的发病率和遗传变异情况，并了解由 IEM 和其中的变异引起的疾病谱。
回顾性分析 2016 年至 2021 年采用串联质谱法（MS/MS）进行的 NBS。所有新生儿在出生后 72 小时采集足跟血。进行靶向大规模平行测序进行基因分析。
在 245194 名新生儿中，有 95 名被诊断为 IEM，总体发病率为 IEM：1/2581；氨基酸代谢障碍：1/4715；有机酸代谢障碍：1/11676；脂肪酸代谢障碍：1/11145。不同 IEM 的发病率范围为 1/245194 至 1/6452。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，发现常见的热点变异为 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；MMA 的 MMACHC 基因：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。
本研究显示了中国东部沿海地区 IEM 的疾病和不同疾病谱。通过 MS/MS 联合大规模平行测序实施 IEM 的 NBS，可以为 IEM 的 NBS 检测提供改进方案。
