Long-term outcomes of enzyme replacement therapy from a large cohort of Korean patients with mucopolysaccharidosis IVA (Morquio A syndrome)

Mucopolysaccharidosis (MPS) IVA (Morquio A syndrome) is an autosomal recessive lysosomal storage disorder caused by a mutation affecting the enzyme N-acetylgalactosamine-6-sulfatase (EC 3.1.6.4, GALNS). Enzyme replacement therapy (ERT) has been shown to improve physical performance, quality of life,...

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Main Authors: Juyoung Sung, Insung Kim, Minji Im, Yoon Ji Ahn, Sang-Mi Kim, Ja-Hyun Jang, Hyung-Doo Park, Tae Yeon Jeon, Kyung Rae Ko, Se-Jun Park, Jun Hwa Lee, Eun Young Kim, Chong Kun Cheon, Eungu Kang, Jung-eun Moon, Young Bae Sohn, Hsiang-Yu Lin, Chih-Kuang Chuang, Shuan-Pei Lin, Sung Yoon Cho
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Molecular Genetics and Metabolism Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2214426925000047
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author Juyoung Sung
Insung Kim
Minji Im
Yoon Ji Ahn
Sang-Mi Kim
Ja-Hyun Jang
Hyung-Doo Park
Tae Yeon Jeon
Kyung Rae Ko
Se-Jun Park
Jun Hwa Lee
Eun Young Kim
Chong Kun Cheon
Eungu Kang
Jung-eun Moon
Young Bae Sohn
Hsiang-Yu Lin
Chih-Kuang Chuang
Shuan-Pei Lin
Sung Yoon Cho
author_facet Juyoung Sung
Insung Kim
Minji Im
Yoon Ji Ahn
Sang-Mi Kim
Ja-Hyun Jang
Hyung-Doo Park
Tae Yeon Jeon
Kyung Rae Ko
Se-Jun Park
Jun Hwa Lee
Eun Young Kim
Chong Kun Cheon
Eungu Kang
Jung-eun Moon
Young Bae Sohn
Hsiang-Yu Lin
Chih-Kuang Chuang
Shuan-Pei Lin
Sung Yoon Cho
author_sort Juyoung Sung
collection DOAJ
description Mucopolysaccharidosis (MPS) IVA (Morquio A syndrome) is an autosomal recessive lysosomal storage disorder caused by a mutation affecting the enzyme N-acetylgalactosamine-6-sulfatase (EC 3.1.6.4, GALNS). Enzyme replacement therapy (ERT) has been shown to improve physical performance, quality of life, and respiratory function in patients with MPS IVA; however, owing to the rarity of MPS IVA, data on Korean patient characteristics are limited. This retrospective study reports clinical, radiographic, biochemical, and molecular findings, and analyzes long-term clinical outcomes, from the largest cohort of Korean patients with MPS IVA in a single center. The analysis included 17 patients from 14 families (58.8 % females; median [range] age at diagnosis 5.2 [1.8–33.7] years). The majority of patients (64.7 %) were classified as having a severe phenotype, 23 % had an intermediate phenotype, and 11.8 % had an attenuated phenotype. Skeletal manifestations and radiologic abnormalities at initial diagnosis included gait abnormality (35.3 %), short stature (23.5 %), chest deformity (23.5 %), scoliosis (17.6 %), kyphosis (11.8 %), dysmorphic face (6 %), hip pain (6 %), and leg deformity (6 %). Twelve different GALNS mutations were identified. Patients received ERT for a median (range) 7.4 years (3.0–12.1). Twelve patients reached final adult height, and all patients with the severe/intermediate phenotype had short stature (<3rd percentile). Hemiepiphysiodesis was the most common surgical intervention among patients with the severe/intermediate phenotype. Drug-related adverse events (urticaria, rash, and anaphylaxis) were reported in four patients but were managed with antihistamines or desensitization. At follow-up, patients experienced improvements in functional independence measure score, ejection fraction, and the 6-min walk test compared with the pre-treatment baseline. This study provides real-world evidence for long-term stabilization of functional independence, endurance, and respiratory function among patients with MPS IVA treated with ERT, with no new safety concerns identified.
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spelling doaj-art-079d6781750d4bd68ee104f772ee66f22025-08-20T02:45:56ZengElsevierMolecular Genetics and Metabolism Reports2214-42692025-03-014210118910.1016/j.ymgmr.2025.101189Long-term outcomes of enzyme replacement therapy from a large cohort of Korean patients with mucopolysaccharidosis IVA (Morquio A syndrome)Juyoung Sung0Insung Kim1Minji Im2Yoon Ji Ahn3Sang-Mi Kim4Ja-Hyun Jang5Hyung-Doo Park6Tae Yeon Jeon7Kyung Rae Ko8Se-Jun Park9Jun Hwa Lee10Eun Young Kim11Chong Kun Cheon12Eungu Kang13Jung-eun Moon14Young Bae Sohn15Hsiang-Yu Lin16Chih-Kuang Chuang17Shuan-Pei Lin18Sung Yoon Cho19Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaDepartment of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaDepartment of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaDepartment of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaDepartment of Laboratory Medicine, Chosun University Hospital, Chosun University School of Medicine, Gwangju, Republic of KoreaDepartment of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaDepartment of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaDepartment of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaDepartment of Orthopedic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaDepartment of Orthopedic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaDepartment of Pediatrics, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of KoreaDepartment of Pediatrics, Chosun University Hospital, Chosun University College of Medicine, Gwangju, Republic of KoreaDepartment of Pediatrics, Pusan National University Children's Hospital, Pusan National University School of Medicine, Yangsan, Republic of KoreaDepartment of Pediatrics, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Republic of KoreaDepartment of Pediatrics, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of KoreaDepartment of Medical Genetics, Ajou University Hospital, Ajou University School of Medicine, Suwon, Republic of KoreaDepartment of Pediatrics, MacKay Memorial Hospital, Taipei 10449, Taiwan; Division of Genetics and Metabolism, Department of Medical Research, MacKay Memorial Hospital, Taipei 10449, Taiwan; Department of Medicine, MacKay Medical College, New Taipei City 252, TaiwanDivision of Genetics and Metabolism, Department of Medical Research, MacKay Memorial Hospital, Taipei 10449, TaiwanDepartment of Pediatrics, MacKay Memorial Hospital, Taipei 10449, Taiwan; Division of Genetics and Metabolism, Department of Medical Research, MacKay Memorial Hospital, Taipei 10449, Taiwan; Department of Medicine, MacKay Medical College, New Taipei City 252, TaiwanDepartment of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Corresponding author at: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea.Mucopolysaccharidosis (MPS) IVA (Morquio A syndrome) is an autosomal recessive lysosomal storage disorder caused by a mutation affecting the enzyme N-acetylgalactosamine-6-sulfatase (EC 3.1.6.4, GALNS). Enzyme replacement therapy (ERT) has been shown to improve physical performance, quality of life, and respiratory function in patients with MPS IVA; however, owing to the rarity of MPS IVA, data on Korean patient characteristics are limited. This retrospective study reports clinical, radiographic, biochemical, and molecular findings, and analyzes long-term clinical outcomes, from the largest cohort of Korean patients with MPS IVA in a single center. The analysis included 17 patients from 14 families (58.8 % females; median [range] age at diagnosis 5.2 [1.8–33.7] years). The majority of patients (64.7 %) were classified as having a severe phenotype, 23 % had an intermediate phenotype, and 11.8 % had an attenuated phenotype. Skeletal manifestations and radiologic abnormalities at initial diagnosis included gait abnormality (35.3 %), short stature (23.5 %), chest deformity (23.5 %), scoliosis (17.6 %), kyphosis (11.8 %), dysmorphic face (6 %), hip pain (6 %), and leg deformity (6 %). Twelve different GALNS mutations were identified. Patients received ERT for a median (range) 7.4 years (3.0–12.1). Twelve patients reached final adult height, and all patients with the severe/intermediate phenotype had short stature (<3rd percentile). Hemiepiphysiodesis was the most common surgical intervention among patients with the severe/intermediate phenotype. Drug-related adverse events (urticaria, rash, and anaphylaxis) were reported in four patients but were managed with antihistamines or desensitization. At follow-up, patients experienced improvements in functional independence measure score, ejection fraction, and the 6-min walk test compared with the pre-treatment baseline. This study provides real-world evidence for long-term stabilization of functional independence, endurance, and respiratory function among patients with MPS IVA treated with ERT, with no new safety concerns identified.http://www.sciencedirect.com/science/article/pii/S2214426925000047Dysostosis multiplexElosulfase alfaMorquio A syndromeEnzyme replacement therapyMPS IVAMucopolysaccharidosis
spellingShingle Juyoung Sung
Insung Kim
Minji Im
Yoon Ji Ahn
Sang-Mi Kim
Ja-Hyun Jang
Hyung-Doo Park
Tae Yeon Jeon
Kyung Rae Ko
Se-Jun Park
Jun Hwa Lee
Eun Young Kim
Chong Kun Cheon
Eungu Kang
Jung-eun Moon
Young Bae Sohn
Hsiang-Yu Lin
Chih-Kuang Chuang
Shuan-Pei Lin
Sung Yoon Cho
Long-term outcomes of enzyme replacement therapy from a large cohort of Korean patients with mucopolysaccharidosis IVA (Morquio A syndrome)
Molecular Genetics and Metabolism Reports
Dysostosis multiplex
Elosulfase alfa
Morquio A syndrome
Enzyme replacement therapy
MPS IVA
Mucopolysaccharidosis
title Long-term outcomes of enzyme replacement therapy from a large cohort of Korean patients with mucopolysaccharidosis IVA (Morquio A syndrome)
title_full Long-term outcomes of enzyme replacement therapy from a large cohort of Korean patients with mucopolysaccharidosis IVA (Morquio A syndrome)
title_fullStr Long-term outcomes of enzyme replacement therapy from a large cohort of Korean patients with mucopolysaccharidosis IVA (Morquio A syndrome)
title_full_unstemmed Long-term outcomes of enzyme replacement therapy from a large cohort of Korean patients with mucopolysaccharidosis IVA (Morquio A syndrome)
title_short Long-term outcomes of enzyme replacement therapy from a large cohort of Korean patients with mucopolysaccharidosis IVA (Morquio A syndrome)
title_sort long term outcomes of enzyme replacement therapy from a large cohort of korean patients with mucopolysaccharidosis iva morquio a syndrome
topic Dysostosis multiplex
Elosulfase alfa
Morquio A syndrome
Enzyme replacement therapy
MPS IVA
Mucopolysaccharidosis
url http://www.sciencedirect.com/science/article/pii/S2214426925000047
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