{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T11:00:53Z","timestamp":1790593253319,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    This study investigated long\u2010term cognitive development and genotype\u2013phenotype relationships in patients with Mucopolysaccharidosis Type II (MPS II). A nationwide prospective cohort study was conducted in the Netherlands with cognitive follow\u2010up since 2007. Patients were classified as neuronopathic or non\u2010neuronopathic based on\n                    <jats:italic>iduronate\u20102\u2010sulphatase<\/jats:italic>\n                    (\n                    <jats:italic>IDS<\/jats:italic>\n                    ) genotype; novel variants based on age and intelligence quotient (IQ). IQ and Mental Age (MA) were analysed individually and, using linear mixed\u2010effect models, at group level to compare trajectories by genotype and phenotype. Twenty\u2010three male patients (22 children, 1 adult) underwent 136 cognitive assessments, beginning at a median age of 2.9\u2009years with a median follow\u2010up of 6.3 (range 0\u201313.5) years. IQ and MA trajectories significantly differed between neuronopathic and non\u2010neuronopathic patients (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Non\u2010neuronopathic patients (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20095) showed normal or mildly impaired cognition. Neuronopathic patients (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200918) initially developed normally, then stagnated, plateaued, and declined; IQ fell below 70 at a median age of 4\u2009years. Patients with deletions (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20093) experienced the earliest, most severe impairment (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001), while those with other\n                    <jats:italic>IDS<\/jats:italic>\n                    variants showed more variable trajectories. Neurocognitive patterns diverge early in MPS II, highlighting the importance of understanding genotype\u2010specific developmental trajectories. This insight is essential for guiding timely brain\u2010targeted interventions, ideally initiated before neurocognitive decline begins.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70246","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T06:02:02Z","timestamp":1789106522000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Longitudinal Assessment of Cognitive Development in 23 Patients With Mucopolysaccharidosis (\n                    <scp>MPS<\/scp>\n                    ) Type\n                    <scp>II<\/scp>\n                    : Results of up to 14\u2009Years of Follow\u2010Up"],"prefix":"10.1002","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1037-6510","authenticated-orcid":false,"given":"J. (Julia)","family":"Holdorp","sequence":"first","affiliation":[{"name":"Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center  Rotterdam the Netherlands"},{"name":"Department of Paediatrics Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8700-0591","authenticated-orcid":false,"given":"M. E. (Michelle)","family":"Kruijshaar","sequence":"additional","affiliation":[{"name":"Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center  Rotterdam the Netherlands"},{"name":"Department of Paediatrics Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. A. M. (Audrey)","family":"Vollebregt","sequence":"additional","affiliation":[{"name":"Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center  Rotterdam the Netherlands"},{"name":"Department of Paediatrics Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9004-0836","authenticated-orcid":false,"given":"A. B. (Andre)","family":"Rietman","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry and Psychology Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3033-5391","authenticated-orcid":false,"given":"M. R. K. (Marianne)","family":"Dijkstra","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry and Psychology Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7650-3059","authenticated-orcid":false,"given":"C. (Carina)","family":"Klees","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry and Psychology Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2587-0283","authenticated-orcid":false,"given":"M. (Margreet)","family":"Wagenmakers","sequence":"additional","affiliation":[{"name":"Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center  Rotterdam the Netherlands"},{"name":"Department of Internal Medicine Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. H. P. (Annie)","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0107-6835","authenticated-orcid":false,"given":"E. (Esmee)","family":"Oussoren","sequence":"additional","affiliation":[{"name":"Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center  Rotterdam the Netherlands"},{"name":"Department of Paediatrics Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3359-1324","authenticated-orcid":false,"given":"A. T. (Ans)","family":"van der Ploeg","sequence":"additional","affiliation":[{"name":"Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center  Rotterdam the Netherlands"},{"name":"Department of Paediatrics Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8091-263X","authenticated-orcid":false,"given":"J. M. P. (Hannerieke)","family":"van den Hout","sequence":"additional","affiliation":[{"name":"Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center  Rotterdam the Netherlands"},{"name":"Department of Paediatrics Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.70.7.2134"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2010-1274"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2008-0999"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.1983.tb13794.x"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2019.07.016"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10212"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrrev.2021.108392"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022951"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.13467"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2016.05.003"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2013.162"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161208784705504"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22115490"},{"key":"e_1_2_13_15_1","unstructured":"U.S. Food and Drug Administration \u201cApproval Letter for Tividenofusp alfa\u2010eknm \u201d2016."},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2508681"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2020.100630"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-023-02805-3"},{"key":"e_1_2_13_19_1","volume-title":"Global Variome Shared LOVD (LOVD v.3.0 Build 30b)","year":"2025"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2017.05.004"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2020.08.007"},{"key":"e_1_2_13_22_1","volume-title":"Bayley Scales of Infant and Toddler Development","author":"Bayley N.","year":"2006"},{"key":"e_1_2_13_23_1","volume-title":"The Abilities of Young Children: A Comprehensive System of Mental Measurement for the First Eight Years of Life","author":"Griffiths R.","year":"1984"},{"key":"e_1_2_13_24_1","volume-title":"Kaufman Assessment Battery for Children","author":"Kaufman A. 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