{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T05:54:40Z","timestamp":1773035680693,"version":"3.50.1"},"reference-count":19,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"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":["Intl J of Devlp Neuroscience"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Hereditary spastic paraplegia (HSP) represents a genetically heterogeneous group of neurodegenerative disorders characterized by progressive axonal degeneration of corticospinal upper motor neurons, leading to lower limb\u2010predominant spasticity and weakness. To date, 83 HSP subtypes have been reported, exhibiting either pure or complicated phenotypes. Among these, spastic paraplegia type 64 (SPG64) is an ultra\u2010rare form of complicated HSP caused by biallelic variants in\n                    <jats:italic>ENTPD1<\/jats:italic>\n                    , which encodes an ectonucleotidase involved in purine metabolism. In this study, we report a proband presenting with neurodevelopmental regression, dysmorphic features and sensorimotor polyneuropathy, followed comprehensively for 6\u2009years. Genetic analysis identified a novel homozygous NM_001776:c.1174C&gt;T;p.Gln392Ter variant in\n                    <jats:italic>ENTPD1<\/jats:italic>\n                    . A literature review reveals that 39 individuals with SPG64 have been reported, with clinical manifestations including cognitive decline (38\/39), speech abnormalities (30\/39) and brain malformations (16\/31). However, aspects of the full phenotypic spectrum remain to be fully characterized. Notably, this case represents the first documented patient with long\u2010term follow\u2010up, providing valuable clinical insights into disease progression over time. Neuroimaging in the proband demonstrated the involvement of the posterior limb of the internal capsule and the \u2018ear of the lynx\u2019 sign, which was not previously reported in SPG64. Furthermore, the presence of sensorimotor polyneuropathy supports that neuropathy may be a previously unappreciated component of SPG64. Our findings highlight the importance of deep phenotyping and long\u2010term follow\u2010up in fully understanding the nature of this unique HSP subtype.\n                  <\/jats:p>","DOI":"10.1002\/jdn.70046","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T09:35:14Z","timestamp":1755596114000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Long\u2010Term Clinical Characterization of\n                    <i>ENTPD1<\/i>\n                    \u2010Related Spastic Paraplegia: A Novel Variant and Comprehensive Literature Review"],"prefix":"10.1002","volume":"85","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2400-8344","authenticated-orcid":false,"given":"Dilsu\u00a0Dicle","family":"Erkan","sequence":"first","affiliation":[{"name":"Department of Medical Genetics Hacettepe University Faculty of Medicine  Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1272-6784","authenticated-orcid":false,"given":"O\u011fuz","family":"Lafc\u0131","sequence":"additional","affiliation":[{"name":"Radiology Dr Nafiz Korez Sincan State Hospital  Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00dclk\u00fchan","family":"\u00d6ztoprak","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Division of Paediatric Neurology Hacettepe University Faculty of Medicine  Ankara Turkey"},{"name":"Paediatric Neurology Dr Sami Ulus Maternity and Children's Health and Disease Training and Research Hospital  Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1813-275X","authenticated-orcid":false,"given":"G\u00f6knur","family":"Halilo\u011flu","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Division of Paediatric Neurology Hacettepe University Faculty of Medicine  Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7683-371X","authenticated-orcid":false,"given":"Naz","family":"G\u00fcleray","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Hacettepe University Faculty of Medicine  Ankara Turkey"},{"name":"Medical Genetics Dr Sami Ulus Maternity and Children's Health and Disease Training and Research Hospital  Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,19]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2008.10.001"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/mdc3.13606"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978\u20100\u2010444\u201064076\u20105.00041\u20107"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26381"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/12447"},{"key":"e_1_2_10_7_1","first-page":"469","article-title":"Sensorimotor Polyneuropathy Is an Underestimated Feature of ENTPD1 Associated Spastic Paraplegia","volume":"31","author":"Erkan D. D.","year":"2023","journal-title":"European Journal of Human Genetics"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.2337\/db06\u20101593"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20163848"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A1483"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24496"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431\u2010018\u20100098\u20102"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41439\u2010018\u20100036\u20104"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1247363"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62878"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2022.114203"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A5935"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/01677063.2021.1895146"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048\u2010018\u20100545\u20109"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11302\u2010020\u201009755\u20106"}],"container-title":["International Journal of Developmental Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jdn.70046","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jdn.70046","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jdn.70046","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T04:56:41Z","timestamp":1773032201000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jdn.70046"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":19,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1002\/jdn.70046"],"URL":"https:\/\/doi.org\/10.1002\/jdn.70046","archive":["Portico"],"relation":{},"ISSN":["0736-5748","1873-474X"],"issn-type":[{"value":"0736-5748","type":"print"},{"value":"1873-474X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8]]},"assertion":[{"value":"2025-03-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70046"}}