{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:18:22Z","timestamp":1790817502469,"version":"4.1.0"},"reference-count":120,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health (NIH)","award":["1R01HD102545-01A1"],"award-info":[{"award-number":["1R01HD102545-01A1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mucopolysaccharidosis type IVA (MPS IVA, Morquio A syndrome) is a rare inherited disorder characterized by skeletal dysplasia due to deficient N-acetylgalactosamine-6-sulfate sulfatase activity, resulting in glycosaminoglycan (GAG) accumulation. Identifying accurate biomarkers reflecting clinical severity and therapeutic response remains challenging. This study evaluated potential surrogate biomarkers, including N-terminal pro-C-type natriuretic peptide (NT-proCNP), collagen types I and II, mono-sulfated keratan sulfate (KS), di-sulfated KS, and chondroitin-6-sulfate (C6S), in blood and urine samples from 60 patients ranging from 1 to 62 years of age. NT-proCNP levels were significantly elevated in patients of all ages and negatively correlated with growth impairment, especially after 8 years of age. Collagen type I levels significantly increased in adult patients, whereas collagen type II showed age-dependent elevations. Urinary KS, in mono- and di-sulfated forms, demonstrated moderate negative correlations with growth impairment. Moreover, NT-proCNP, mono- and di-sulfated KS in plasma, and urinary di-sulfated KS were not affected by enzyme replacement therapy in patients younger than 12 years, unlike urinary mono-sulfated KS. In conclusion, NT-proCNP has emerged as a promising independent biomarker reflecting the severity of skeletal dysplasia and possibly the near-future growth rate. These findings highlight the potential role of NT-proCNP in clinical assessment and monitoring therapeutic efficacy, addressing current unmet needs in MPS IVA management.<\/jats:p>","DOI":"10.3390\/ijms26104940","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T07:44:57Z","timestamp":1747813497000},"page":"4940","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Identification of Surrogate Biomarkers for Mucopolysaccharidosis Type IVA"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5307-3658","authenticated-orcid":false,"given":"Yasuhiko","family":"Ago","sequence":"first","affiliation":[{"name":"Nemours Children\u2019s Health, Wilmington, DE 19803, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaukat","family":"Khan","sequence":"additional","affiliation":[{"name":"Nemours Children\u2019s Health, Wilmington, DE 19803, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Klipner","sequence":"additional","affiliation":[{"name":"Nemours Children\u2019s Health, Wilmington, DE 19803, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3586-8807","authenticated-orcid":false,"given":"Allison","family":"Bradford","sequence":"additional","affiliation":[{"name":"Nemours Children\u2019s Health, Wilmington, DE 19803, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0673-2160","authenticated-orcid":false,"given":"Shunji","family":"Tomatsu","sequence":"additional","affiliation":[{"name":"Nemours Children\u2019s Health, Wilmington, DE 19803, USA"},{"name":"Faculty of Arts and Sciences, University of Delaware, Newark, DE 19716, USA"},{"name":"Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu 501-1193, Japan"},{"name":"Department of Pediatrics, Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.ymgme.2018.01.003","article-title":"Clinical Presentation and Diagnosis of Mucopolysaccharidoses","volume":"125","author":"Stapleton","year":"2018","journal-title":"Mol. 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