{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:18:15Z","timestamp":1790752695934,"version":"4.1.0"},"reference-count":27,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,2,2]],"date-time":"2020-02-02T00:00:00Z","timestamp":1580601600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: Morquio A syndrome, mucopolysaccharidosis type IVA (MPS IVA), is a lysosomal storage disorder caused by the deficient activity of N-acetylgalactosamine-6-sulfatase (GalNac6S), due to alterations in the GALNS gene. This disorder results in marked abnormalities in bones and connective tissues, and affects multiple organs. Here, we describe the clinical course of a Japanese boy with MPS IVA who began enzyme replacement therapy (ERT) at the age of 24 months. Patient: the patient presented for kyphosis treatment at 22 months of age. An X-ray examination revealed dysostosis multiplex. Uronic acids were elevated in the urine and the keratan sulfate (KS) fraction was predominant. The leukocyte GalNac6S enzyme activity was extremely low. The patient exhibited the c.463G &gt; A (p.Gly155Arg) mutation in GALNS. Based on these findings, his disease was diagnosed as classical (severe) Morquio A syndrome. An elosulfase alfa infusion was initiated at the age of 24 months. The patient\u2019s body height improved from \u22122.5 standard deviation (SD) to \u22122 SD and his physical activity increased during the first 9 months on ERT. However, he gradually developed paralysis in the lower legs with declining growth velocity, which required cervical decompression surgery in the second year of the ERT. The mild mitral regurgitation, serous otitis media, and mild hearing loss did not progress during treatment. Conclusion: early initiation of the elosulfase alfa to our patient showed good effects on the visceral system and muscle strength, while its effect on bones appeared limited. Careful observation is necessary to ensure timely surgical intervention for skeletal disorders associated with neurological symptoms. Centralized and multidisciplinary management is essential to improve the prognosis of pediatric patients with MPS IVA.<\/jats:p>","DOI":"10.3390\/ijms21030989","type":"journal-article","created":{"date-parts":[[2020,2,3]],"date-time":"2020-02-03T11:28:31Z","timestamp":1580729311000},"page":"989","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["A Case Report of a Japanese Boy with Morquio A Syndrome: Effects of Enzyme Replacement Therapy Initiated at the Age of 24 Months"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7417-8923","authenticated-orcid":false,"given":"Akari","family":"Nakamura-Utsunomiya","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima 7348511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshio","family":"Nakamae","sequence":"additional","affiliation":[{"name":"Department of Orthopeadic Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 7348551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reiko","family":"Kagawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima 7348511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhei","family":"Karakawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima 7348511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonoko","family":"Sakata","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima 7348511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumiaki","family":"Sakura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima 7348511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chihiro","family":"Tani","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Radiology, Hiroshima University Hospital, Hiroshima 7348551, Japan"},{"name":"Department of Diagnostic Radiology, Hiroshima Citizen\u2019s Hospital, Hiroshima 7308518, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiko","family":"Matsubara","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Radiology, Hiroshima University Hospital, Hiroshima 7348551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Ishino","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Hiroshima University Hospital, Hiroshima 7348551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Go","family":"Tajima","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima 7348511, Japan"},{"name":"Division of Neonatal Screening, Research Institute, National Center for Child Health and Development, Tokyo 1578535, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4622-5657","authenticated-orcid":false,"given":"Satoshi","family":"Okada","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima 7348511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.ymgme.2016.11.007","article-title":"Mucopolysaccaridosis \u2163A and glycosaminoglycans","volume":"120","author":"Khan","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.2174\/138161209787846739","article-title":"Cartilage and bone extracellular matrix","volume":"15","author":"Gentili","year":"2009","journal-title":"Curr. Pharm. Des."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ymgme.2018.05.004","article-title":"Molecular genetics and metabolism special edition: Diagnosis and prognosis of mucopolysaccharidosis IVA","volume":"125","author":"Perache","year":"2018","journal-title":"Mol. Genet. Metab."},{"key":"ref_4","first-page":"129","article-title":"Chondroitin sulfate and growth factor signaling in the skeleton: Possible link to MPS \u2165","volume":"3","author":"Aliiston","year":"2010","journal-title":"J. Pediatr. Rehabil. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.prrv.2010.10.005","article-title":"Respiratory manifestations in mucopolysaccharidoses","volume":"12","author":"Muhlebach","year":"2011","journal-title":"Pediatr. Respir."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.ymgme.2015.09.007","article-title":"Obstructive airway in Morquio A syndrome, the past, the present and the future","volume":"117","author":"Tomatsu","year":"2016","journal-title":"Mol. Genet. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.ymgme.2009.03.008","article-title":"Deficiency in N-acetylgalactosamine-6-sulfate sulfatase results in collagen perturbations in cartilage of Morquio syndrome A patients","volume":"97","author":"Bank","year":"2009","journal-title":"Mol. Genet. Metab."},{"key":"ref_8","first-page":"65","article-title":"Current and emerging treatments and surgical interventions for Morquio A syndrome: A review","volume":"12","author":"Tomatsu","year":"2012","journal-title":"Res. Rep. Endocr. Disord."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"931","DOI":"10.2174\/138920111795542615","article-title":"Mucopolysaccharidosis type IVA (Morquio A disease): Clinical review and current treatment","volume":"12","author":"Tomatsu","year":"2011","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1002\/humu.20257","article-title":"Mutation and polymorphism spectrum of the GALNS gene in mucopolysaccharidosis 4A","volume":"26","author":"Tomatsu","year":"2005","journal-title":"Hum. Mutat."},{"key":"ref_11","first-page":"76","article-title":"Elosulfase alfa enzyme replacement therapy attenuates disease progression in a non-ambulatory Japanese patient with Morquio A syndrome (case report)","volume":"13","author":"Hiramatsu","year":"2017","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1038\/pr.2015.169","article-title":"Safety and clinical activity of elosulfase alfa in pediatric patients with Morquio A syndrome (mucopolysaccharidosis IVA) less than 5 y","volume":"78","author":"Jones","year":"2015","journal-title":"Pediatr. Res."},{"key":"ref_13","first-page":"42","article-title":"30 months follow-up of an early enzyme replacement therapy in a severe Morquio A patient: About one case","volume":"9","author":"Wiedemann","year":"2016","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/s10038-019-0604-6","article-title":"Effect of enzyme replacement therapy on the growth of patients with Morquio A","volume":"64","author":"Doherty","year":"2019","journal-title":"J. Hum. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.ymgme.2016.05.003","article-title":"Molecular diagnosis of 65 families with mucopolysaccharidosis type II (Hunter syndrome) characterized by 16 novel mutations in the IDS gene: Genetic, pathological, and structural studies on iduronate-2-sulfatase","volume":"118","author":"Kosuga","year":"2016","journal-title":"Mol. Genet. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1002\/ajmg.a.32281","article-title":"Growth charts for patients affected with Morquio A disease","volume":"146","author":"Montano","year":"2008","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Preedy, V.R. (2012). Impairment of Body Growth in Mucopolysaccharidoses. Handbook of Growth and Growth Monitoring in Health and Disease, Springer Science & Business Media, LLC.","DOI":"10.1007\/978-1-4419-1795-9"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1297\/cpe.25.71","article-title":"Growth standard charts for Japanese children with mean and standard deviation (SD) values based on the year 2000 national survey","volume":"25","author":"Kato","year":"2016","journal-title":"Clinic Pediatr. Endocrinol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.ymgme.2014.10.010","article-title":"Diagnostic evaluation, monitoring, and perioperative management of spinal cord compression in patients with Morquio syndrome","volume":"114","author":"Charrow","year":"2015","journal-title":"Mol. Genet. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"112","DOI":"10.2353\/ajpath.2008.070564","article-title":"Mechanism of glycosaminoglycan-mediated bone and joint disease; implications for the mucopolysaccharidoses and other connective tissue disease","volume":"172","author":"Simonaro","year":"2008","journal-title":"Am. J. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/0006-291X(74)91022-5","article-title":"Morquio\u2019s syndrome: Deficiency of a chondroitin sulfate N-acetylhexosamine sulfate sulfatase","volume":"61","author":"Matalon","year":"1974","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.ymgmr.2017.11.005","article-title":"Natural history of Morquio A patient with tracheal obstruction from birth to death","volume":"1","author":"Doherty","year":"2018","journal-title":"Mol. Genet. Metab. Reports."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ymgme.2018.03.004","article-title":"Growth impairment in mucopolysaccharidoses","volume":"124","author":"Melbouc","year":"2018","journal-title":"Mol. Genet. Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1073\/pnas.0912937107","article-title":"Involvement of the Toll-like receptor 4 pathway and use of TNF-alpha antagonists for treatment of the mucopolysaccharidoses","volume":"107","author":"Simonaro","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s13052-019-0691-1","article-title":"The use of recombinant human growth hormone in patients with Mucopolysaccharidosis and growth hormone deficiency: A case series","volume":"45","author":"Cattoni","year":"2019","journal-title":"Ital. J. Pediatrics."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Schuchman, E.H., Ge, Y., Lai, A., Borisov, Y., Faillace, M., Eliyahu, E., He, X., Iatridis, J., Vlassara, H., and Striker, G. (2013). Pentosan polysulfate: A novel therapy for the mucopolysaccharidoses. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0054459"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"\u00c1lvarez, J., Bravo, S.B., Garc\u00eda-Vence, M., De Castro, M.J., Luzardo, A., Col\u00f3n, C., Tomatsu, S., Otero-Espinar, F.J., and Couce, M. (2019). Proteomic analysis in Morquio A cells treated with immobilized enzymatic replacement therapy on nanostructured lipid systems. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184610"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/3\/989\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T08:53:57Z","timestamp":1760172837000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/3\/989"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,2]]},"references-count":27,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,2]]}},"alternative-id":["ijms21030989"],"URL":"https:\/\/doi.org\/10.3390\/ijms21030989","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,2]]}}}