2015—2022年嘉兴市基于串联质谱技术新生儿遗传代谢病筛查及确诊患儿基因变异谱分析

doi:10.11852/zgetbjzz2024-1139

中国儿童保健杂志 ›› 2025, Vol. 33 ›› Issue (6): 664-670.DOI: 10.11852/zgetbjzz2024-1139

2015—2022年嘉兴市基于串联质谱技术新生儿遗传代谢病筛查及确诊患儿基因变异谱分析

丁洁^1*, 张婷^2*, 韩新儒¹, 刘惠娟¹, 张莺¹, 戴艳¹, 李晶¹, 杨茹莱²

1.嘉兴市妇幼保健院儿童保健科,浙江嘉兴 314001;
2.浙江大学医学院附属儿童医院遗传与代谢科,浙江杭州 310052

收稿日期:2024-09-21 修回日期:2025-02-02 发布日期:2025-06-05 出版日期:2025-06-10
通讯作者: 李晶,E-mail:8242649@qq.com;杨茹莱,E-mail:chsczx@zju.edu.cn
作者简介:丁洁(1986—),女,本科学历,主治医师,主要研究方向为新生儿疾病筛查管理及儿童生长发育;张婷(1988—),女,硕士学位,副主任技师,主要研究方向为遗传代谢病的分子诊断。
注:^*共同第一作者。
基金资助:
国家重点研发计划(2022YFC2703401)

Screening results of inborn errors of metabolism based on tandem mass spectrometry and gene variation spectrum analysis of confirmed children in Jiaxing City from 2015 to 2022

DING Jie^1*, ZHANG Ting^2*, HAN Xinru¹, LIU Huijuan¹, ZHANG Ying¹, DAI Yan¹, LI Jing¹, YANG Rulai²

1. Department of Child Health, Jiaxing Maternal and Child Health Care Hospital, Jiaxing, Zhejiang 314001, China;
2. Genetics & Metabolism Department of Children′s Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310052, China

Received:2024-09-21 Revised:2025-02-02 Online:2025-06-10 Published:2025-06-05
Contact: LI Jing,E-mail:8242649@qq.com; YANG Rulai,E-mail:chsczx@zju.edu.cn

摘要/Abstract

摘要： 目的采用串联质谱(MSMS)技术筛查遗传代谢病情况并进行分析,明确嘉兴市遗传代谢病流行病学特点及基因变异谱,为预防新生儿出生缺陷提供科学依据。方法对嘉兴市2015年1月—2022年12月出生的新生儿取足跟血采用MSMS法进行初筛,初筛阳性者予以召回复查并进行生化和基因检测,结合临床表现明确诊断,回顾性分析其发病率及基因变异。结果 2015—2022年全市活产新生儿为376 649名,总筛查人数375 562名,采用MSMS法筛查328 660名,平均筛查率为87.26%且逐年上升。确诊氨基酸代谢障碍(AAD)、脂肪酸β氧化障碍(FAOD)、有机酸代谢障碍(OAD)三大类疾病患儿85例,总发病率为1/3 867。高苯丙氨酸血症、原发性肉碱缺乏症和甲基丙二酸血症分别为AAD、FAOD和OAD中最常见的病种,发病率分别为1/14 290、1/21 911和1/54 777。基因分析共发现90种基因变异,最常见为PAH基因的c.728G>A、c.1068C>A和c.721C>T变异,ACADSB基因的c.1165G>A变异,SLC22A5基因的c.1400C>G、c.51C>G变异和SLC25A13基因的c.615+5G>A变异。结论嘉兴市实现了对新生儿遗传代谢病的早期筛查和诊治,明确了该类疾病的发病率和基因变异谱,对加强出生缺陷防控、提高出生人口质量具有重大意义。

关键词: 串联质谱技术, 新生儿, 遗传代谢病, 基因变异谱

Abstract: Objective To analyze the profile of inborn errors of metabolism (IEM) using tandem mass spectrometry (MSMS) screening, and to clarify the epidemiological characteristics and genetic variant spectrum in Jiaxing City, in order to provide a scientific basis for the prevention of neonatal birth defects. Methods Heel blood samples from newborns born in Jiaxing City between January 2015 and December 2022 were initially screened by MSMS.Positive cases were recalled for retesting, followed by biochemical and genetic analyses.Diagnoses were confirmed based on clinical manifestations, and the incidence rates and genetic variants were retrospectively analyzed. Results Among 376 649 live births during the study period, 375 562 neonates were screened, with 328 660 undergoing MSMS screening (average screening rate: 87.26%, increasing annually).A total of 85 cases were diagnosed with amino acid disorders (AADs), fatty acid oxidation disorders (FAOD), or organic acid disorders (OAD), yielding an overall incidence of 1/3 867.Hyperphenylalaninemia, primary carnitine deficiency, and methylmalonic acidemia were the most prevalent conditions in AADs, FAODs, and OADs, with incidences of 1/14 290, 1/21 911, and 1/54 777, respectively.Genetic analysis identified 90 pathogenic variants, with the most frequent being PAH c.728G>A, c.1068C>A, and c.721C>T; ACADSB c.1165G>A; SLC22A5 c.1400C>G and c.51C>G; and SLC25A13 c.615+5G>A. Conclusions This study clarifies the incidence and genetic variant spectrum of neonatal IEM in the region, enabling early screening, diagnosis, and intervention in Jiaxing City.These findings are critical for strengthening birth defect prevention and improving neonatal health outcomes.

Key words: tandem mass spectrometry, newborn, inborn errors of metabolism, gene variation spectrum

中图分类号:

R179

丁洁, 张婷, 韩新儒, 刘惠娟, 张莺, 戴艳, 李晶, 杨茹莱. 2015—2022年嘉兴市基于串联质谱技术新生儿遗传代谢病筛查及确诊患儿基因变异谱分析[J]. 中国儿童保健杂志, 2025, 33(6): 664-670.

DING Jie, ZHANG Ting, HAN Xinru, LIU Huijuan, ZHANG Ying, DAI Yan, LI Jing, YANG Rulai. Screening results of inborn errors of metabolism based on tandem mass spectrometry and gene variation spectrum analysis of confirmed children in Jiaxing City from 2015 to 2022[J]. Chinese Journal of Child Health Care, 2025, 33(6): 664-670.

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2015—2022年嘉兴市基于串联质谱技术新生儿遗传代谢病筛查及确诊患儿基因变异谱分析

Screening results of inborn errors of metabolism based on tandem mass spectrometry and gene variation spectrum analysis of confirmed children in Jiaxing City from 2015 to 2022

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