台湾地区IVA型黏多糖贮积症新生儿筛查的实施与长期监测

Implementation of newborn screening for mucopolysaccharidosis type IVA and long-term monitoring in Taiwan.

作者信息

Lin Hsiang-Yu, Lee Chung-Lin, Chang Ya-Hui, Tu Yuan-Rong, Lo Yun-Ting, Wu Jun-Yi, Niu Dau-Ming, Liu Mei-Ying, Liu Hsin-Yun, Chen Hsiao-Jan, Kao Shu-Min, Wang Li-Yun, Ho Huey-Jane, Chuang Chih-Kuang, Lin Shuan-Pei

机构信息

Department of Pediatrics, MacKay Memorial Hospital, Taipei, Taiwan; Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan; The Rare Disease Center, MacKay Memorial Hospital, Taipei, Taiwan; Department of Medicine, MacKay Medical College, New Taipei City, Taiwan; MacKay Junior College of Medicine, Nursing and Management, Taipei, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.

出版信息

Genet Med. 2024 Dec;26(12):101286. doi: 10.1016/j.gim.2024.101286. Epub 2024 Oct 4.

DOI:10.1016/j.gim.2024.101286

PMID:39375993

Abstract

PURPOSE

Mucopolysaccharidosis IVA (MPS IVA) is a rare lysosomal storage disorder arising from a deficiency in N-acetylgalactosamine-6-sulfatase.

METHODS

From September 2019 to October 2023, a total of 264,843 Taiwanese newborns underwent screening for MPS IVA using dried blood spots and tandem mass spectrometry.

RESULTS

Among the 95 referred infants, 9 (9%) were confirmed to have MPS IVA (group 1), 18 (19%) were highly suspected to have MPS IVA (group 2), 61 (64%) were identified as heterozygotes of MPS IVA (group 3), and 7 (7%) were determined not to have MPS IVA (group 4). A total of 34 different GALNS (HGNC:4122) gene variants were identified through our MPS IVA newborn screening program. The most prevalent variant was c.857C>T p.(Thr286Met), found in 33 cases (29%), followed by c.953T>G p.(Met318Arg) in 22 cases (19%). Intravenous enzyme replacement therapy was initiated in 5 patients at ages ranging from 0.3 to 1.7 years. The estimated incidence of MPS IVA in this screening program was 3.4 per 100,000 live births.

CONCLUSION

Because of the progressive nature of MPS IVA, an early diagnosis facilitated by newborn screening and prompt initiation of enzyme replacement therapy before irreversible organ damage occurs may result in improved clinical outcomes.

摘要

目的

IVA型黏多糖贮积症（MPS IVA）是一种罕见的溶酶体贮积病，由N-乙酰半乳糖胺-6-硫酸酯酶缺乏引起。

方法

2019年9月至2023年10月，共有264,843名台湾新生儿使用干血斑和串联质谱法进行了MPS IVA筛查。

结果

在95名转诊婴儿中，9名（9%）被确诊为MPS IVA（第1组），18名（19%）高度怀疑患有MPS IVA（第2组），61名（64%）被鉴定为MPS IVA杂合子（第3组），7名（7%）被确定没有MPS IVA（第4组）。通过我们的MPS IVA新生儿筛查项目共鉴定出34种不同的GALNS（HGNC:4122）基因变异。最常见的变异是c.857C>T p.(Thr286Met)，在33例（29%）中发现，其次是c.953T>G p.(Met318Arg)，在22例（19%）中发现。5例年龄在0.3至1.7岁的患者开始接受静脉酶替代治疗。该筛查项目中MPS IVA的估计发病率为每10万活产3.4例。