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

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

doi:10.1016/j.gim.2024.101286

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

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

Authors

Hsiang-Yu Lin¹, Chung-Lin Lee², Ya-Hui Chang³, Yuan-Rong Tu⁴, Yun-Ting Lo⁵, Jun-Yi Wu⁵, Dau-Ming Niu⁶, Mei-Ying Liu⁷, Hsin-Yun Liu⁷, Hsiao-Jan Chen⁷, Shu-Min Kao⁷, Li-Yun Wang⁸, Huey-Jane Ho⁸, Chih-Kuang Chuang⁹, Shuan-Pei Lin¹⁰

Affiliations

¹ 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.
² 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.
³ Department of Pediatrics, MacKay Memorial Hospital, Taipei, Taiwan; The Rare Disease Center, MacKay Memorial Hospital, Taipei, Taiwan.
⁴ Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan.
⁵ The Rare Disease Center, MacKay Memorial Hospital, Taipei, Taiwan.
⁶ Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan.
⁷ The Chinese Foundation of Health, Neonatal Screening Center, Taipei, Taiwan.
⁸ Taipei Institute of Pathology, Neonatal Screening Center, Taipei, Taiwan.
⁹ Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan; College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan. Electronic address: [email protected].
¹⁰ 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; Department of Infant and Child Care, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan. Electronic address: [email protected].

PMID: 39375993
DOI: 10.1016/j.gim.2024.101286

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.

Keywords: Enzyme replacement therapy; Genotype-phenotype correlation; Glycosaminoglycans; Mucopolysaccharidosis IVA (MPS IVA); Newborn screening program.

MeSH terms

Chondroitinsulfatases* / genetics
Dried Blood Spot Testing
Enzyme Replacement Therapy
Female
Humans
Infant
Infant, Newborn
Male
Mucopolysaccharidosis IV* / diagnosis
Mucopolysaccharidosis IV* / epidemiology
Mucopolysaccharidosis IV* / genetics
Mutation / genetics
Neonatal Screening* / methods
Taiwan / epidemiology
Tandem Mass Spectrometry

Substances

GALNS protein, human
Chondroitinsulfatases