{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T19:16:48Z","timestamp":1793128608198,"version":"4.5.0"},"reference-count":11,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,2,1]],"date-time":"2018-02-01T00:00:00Z","timestamp":1517443200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,2,1]],"date-time":"2018-02-01T00:00:00Z","timestamp":1517443200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"University Medical Center Utrecht"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>CLN3 disease is a major cause of childhood neurodegeneration. Onset of visual failure around 6 years of age is thought to precede cognitive deterioration by a few years, but casuistic reports question this paradigm. The aim of our study is to delineate timing of cognitive decline in CLN3 disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Early neurocognitive functioning in CLN3 disease was analyzed using age at onset of visual and cognitive decline and IQ scores from literature\u2010derived patient descriptions, supplemented with IQ scores and school history from a retrospective referral center cohort. We analyzed protracted and classical CLN3 separately and added a control group of patients diagnosed with juvenile onset macular degeneration (early onset Stargardt disease) to control for possible effects of rapid vision loss on neurocognitive functioning.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Onset of cognitive decline at a mean age of 6.8 years (range 2\u201313 years, <jats:italic>n<\/jats:italic>\u2009=\u200919) paralleled onset of visual deterioration at a mean age of 6.4 years (range 4\u20139 years, <jats:italic>n<\/jats:italic>\u2009=\u200981) as supported by an early decline in IQ scores in classical CLN3 disease. Onset and course of vision loss was similar in patients with protracted CLN3. The decreased IQ levels at diagnosis (mean 68.4, range 57\u201379, <jats:italic>n<\/jats:italic>\u2009=\u20099) in the referral cohort were consistently associated with an aberrant early school history contrasting normal school history and cognition in Stargardt disease patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Cognitive dysfunction is universally present around diagnosis in classical CLN3 disease.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s10545-018-0143-x","type":"journal-article","created":{"date-parts":[[2018,2,1]],"date-time":"2018-02-01T09:35:51Z","timestamp":1517477751000},"page":"257-261","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Timing of cognitive decline in CLN3 disease"],"prefix":"10.1002","volume":"41","author":[{"given":"Willemijn F. E.","family":"Kuper","sequence":"first","affiliation":[{"name":"Department of Metabolic Diseases, Wilhelmina Children's Hospital University Medical Center Utrecht P.O. Box 85090 Utrecht AB 3508 the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"van Alfen","sequence":"additional","affiliation":[{"name":"Bartim\u00e9us Institute for the visually impaired Zeist and Doorn the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roeliene H.","family":"Rigterink","sequence":"additional","affiliation":[{"name":"Bartim\u00e9us Institute for the visually impaired Zeist and Doorn the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine A.","family":"Fuchs","sequence":"additional","affiliation":[{"name":"Department of Metabolic Diseases, Wilhelmina Children's Hospital University Medical Center Utrecht P.O. Box 85090 Utrecht AB 3508 the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria M.","family":"van Genderen","sequence":"additional","affiliation":[{"name":"Bartim\u00e9us Institute for the visually impaired Zeist and Doorn the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter M.","family":"van Hasselt","sequence":"additional","affiliation":[{"name":"Department of Metabolic Diseases, Wilhelmina Children's Hospital University Medical Center Utrecht P.O. Box 85090 Utrecht AB 3508 the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073807302603"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2012.11.014"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.4915"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/62.1.1"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21624"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.1983.tb13815.x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2014.08.032"},{"issue":"1","key":"e_1_2_10_9_1","first-page":"8","article-title":"Neuropsychological test battery in the follow\u2010up of patients with juvenile neuronal ceroid lipofuscinosis","volume":"45","author":"Lamminranta S","year":"2001","journal-title":"J Intellect Disabil Res"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.52.2.360"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1086\/514846"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.64.10.726"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s10545-018-0143-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10545-018-0143-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10545-018-0143-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-018-0143-x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T01:53:51Z","timestamp":1694742831000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1007\/s10545-018-0143-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2]]},"references-count":11,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,3]]}},"alternative-id":["10.1007\/s10545-018-0143-x"],"URL":"https:\/\/doi.org\/10.1007\/s10545-018-0143-x","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2]]}}}