Lin Hsiang-Yu, Chang Ya-Hui, Lee Chung-Lin, Tu Yuan-Rong, Lo Yun-Ting, Hung Pei-Wen, 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
Department of Pediatrics, MacKay Memorial Hospital, Taipei 10449, Taiwan.
Department of Medical Research, MacKay Memorial Hospital, Taipei 10449, Taiwan.
J Pers Med. 2022 Jun 21;12(7):1023. doi: 10.3390/jpm12071023.
Mucopolysaccharidosis II (MPS II) is an X-linked disorder resulting from a deficiency in lysosomal enzyme iduronate-2-sulfatase (IDS), which causes the accumulation of glycosaminoglycans (GAGs) in the lysosomes of many tissues and organs, leading to progressive cellular dysfunction. An MPS II newborn screening program has been available in Taiwan since 2015. The aim of the current study was to collect and analyze the long-term follow-up data of the screen-positive subjects in this program.
From August 2015 to April 2022, 548,624 newborns were screened for MPS II by dried blood spots using tandem mass spectrometry, of which 202 suspected infants were referred to our hospital for confirmation. The diagnosis of MPS II was confirmed by IDS enzyme activity assay in leukocytes, quantitative determination of urinary GAGs by mass spectrometry, and identification of the gene variant.
Among the 202 referred infants, 10 (5%) with seven gene variants were diagnosed with confirmed MPS II (Group 1), 151 (75%) with nine gene variants were classified as having suspected MPS II or pseudodeficiency (Group 2), and 41 (20%) with five gene variants were classified as not having MPS II (Group 3). Long-term follow-up every 6 months was arranged for the infants in Group 1 and Group 2. Intravenous enzyme replacement therapy (ERT) was started in four patients at 1, 0.5, 0.4, and 0.5 years of age, respectively. Three patients also received hematopoietic stem cell transplantation (HSCT) at 1.5, 0.9, and 0.6 years of age, respectively. After ERT and/or HSCT, IDS enzyme activity and the quantity of urinary GAGs significantly improved in all of these patients compared with the baseline data.
Because of the progressive nature of MPS II, early diagnosis via a newborn screening program and timely initiation of ERT and/or HSCT before the occurrence of irreversible organ damage may lead to better clinical outcomes. The findings of the current study could serve as baseline data for the analysis of the long-term effects of ERT and HSCT in these patients.
黏多糖贮积症II型（MPS II）是一种X连锁疾病，由溶酶体酶艾杜糖醛酸-2-硫酸酯酶（IDS）缺乏引起，导致糖胺聚糖（GAGs）在许多组织和器官的溶酶体中蓄积，进而导致进行性细胞功能障碍。自2015年起，台湾地区开展了MPS II新生儿筛查项目。本研究的目的是收集并分析该项目中筛查阳性受试者的长期随访数据。
2015年8月至2022年4月，采用串联质谱法对548,624名新生儿的干血斑进行MPS II筛查，其中202名疑似婴儿被转诊至我院进行确诊。通过白细胞中的IDS酶活性测定、质谱法定量测定尿GAGs以及鉴定基因变异来确诊MPS II。
在这202名转诊婴儿中，10名（5%）携带7种基因变异被确诊为MPS II（第1组），151名（75%）携带9种基因变异被归类为疑似MPS II或假性缺陷（第2组），41名（20%）携带5种基因变异被归类为无MPS II（第3组）。对第I组和第2组的婴儿每6个月进行一次长期随访。4例患者分别在1岁、0.5岁、0.4岁和0.5岁时开始静脉内酶替代疗法（ERT）。3例患者分别在1.5岁、0.9岁和0.6岁时还接受了造血干细胞移植（HSCT）。与基线数据相比，ERT和/或HSCT后，所有这些患者的IDS酶活性和尿GAGs量均显著改善。
由于MPS II具有进行性特点，通过新生儿筛查项目进行早期诊断，并在不可逆器官损伤发生前及时启动ERT和/或HSCT，可能会带来更好的临床结果。本研究结果可作为分析ERT和HSCT对这些患者长期影响的基线数据。
