{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:12:00Z","timestamp":1790820720708,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T00:00:00Z","timestamp":1729641600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mucopolysaccharidosis II (MPS II, Hunter syndrome) is a rare, X\u2010linked lysosomal storage disease caused by reduced activity of iduronate\u20102\u2010sulfatase (I2S), with subsequent cellular accumulation of the glycosaminoglycans (GAGs), heparan sulfate, and dermatan sulfate (DS). DS is a major component of the extracellular matrix of heart valves, which can be affected in MPS II. We investigated the natural history of valve disease in MPS II and the impact of long\u2010term intravenous enzyme replacement therapy (ERT) with recombinant I2S (idursulfase). In total, 604 cardiac examinations were assessed from serial follow\u2010up of 80 male patients (49 neuronopathic). Valve disease was classified according to standard practice from hemodynamic features evident from echocardiography. The natural history group comprised 48 patients (up to 14.8\u2009years of follow\u2010up; median, 2.6\u2009years; 24 patients started ERT during the study); 56 patients were treated (up to 14.2\u2009years of follow\u2010up; median, 6.2\u2009years). Lifetime GAG burden (calculated from urinary GAG measurements) correlated significantly with the degree of valve disease. Onset of moderate\u2010to\u2010severe valve disease was significantly delayed in treated (median age at onset, 29.1\u2009\u00b1\u20092 [95% CI: 25.2\u201332.9] years; Kaplan\u2013Meier estimation) versus untreated patients (17.6\u2009\u00b1\u20091 [95% Cl: 15.8\u201319.4] years; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). Cox regression modeling found that long\u2010term ERT reduced the probability of developing severe valve disease (<jats:italic>\u03c7<\/jats:italic><jats:sup>2<\/jats:sup>, 32.736; significant after 5\u2009years of ERT). Overall, this study found that valve disease severity in MPS II correlates with GAG burden and that progression is delayed by long\u2010term ERT.<\/jats:p>","DOI":"10.1002\/jimd.12808","type":"journal-article","created":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T04:58:17Z","timestamp":1729659497000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Natural history of valve disease in patients with mucopolysaccharidosis <scp>II<\/scp> and the impact of enzyme replacement therapy"],"prefix":"10.1002","volume":"48","author":[{"given":"Christoph","family":"Kampmann","sequence":"first","affiliation":[{"name":"Department of Pediatric Cardiology and Structural Heart Diseases, Center for Diseases in Childhood and Adolescence University Medicine Mainz  Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Lampe","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, Epileptology and Social Medicine University Hospital Giessen  Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane M.","family":"Wiethoff","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology and Structural Heart Diseases, Center for Diseases in Childhood and Adolescence University Medicine Mainz  Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laila","family":"Arash\u2010Kaps","sequence":"additional","affiliation":[{"name":"SphinCS, Institute of Clinical Science in LSD  Hochheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugen","family":"Mengel","sequence":"additional","affiliation":[{"name":"SphinCS, Institute of Clinical Science in LSD  Hochheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joerg","family":"Reinke","sequence":"additional","affiliation":[{"name":"Medical center for adults with disabilities Kreuznacher Diakonie  Bad Kreuznach Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Beck","sequence":"additional","affiliation":[{"name":"SphinCS, Institute of Clinical Science in LSD  Hochheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia B.","family":"Hennermann","sequence":"additional","affiliation":[{"name":"Department of Metabolic Diseases, Villa Metabolica, Center for Diseases in Childhood and Adolescence University Medicine Mainz  Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6576-7072","authenticated-orcid":false,"given":"Tariq","family":"Abu\u2010Tair","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology and Structural Heart Diseases, Center for Diseases in Childhood and Adolescence University Medicine Mainz  Mainz 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