{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T08:22:34Z","timestamp":1740126154121,"version":"3.37.3"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,7,6]],"date-time":"2015-07-06T00:00:00Z","timestamp":1436140800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Adult\u2010onset orthochromatic leucodystrophy, associated with pigmented macrophages and hereditary diffuse leucoencephalopathy with spheroids, are two disorders with similar clinical manifestations, radiological characteristics and neuropathological findings. Mutations in the colony\u2010stimulating factor 1 receptor (<jats:italic><jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content>1R<\/jats:italic>) gene are the hallmark of this spectrum of disease. Furthermore, polycystic membranous lipomembranous osteodysplasia with sclerosing leucoencephalopathy is caused by mutations in two genes, <jats:italic><jats:styled-content style=\"fixed-case\">DAP<\/jats:styled-content>12<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">TREM<\/jats:styled-content>2<\/jats:italic>, which encode proteins involved in the same pathways as <jats:italic><jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content>1R<\/jats:italic>. We describe a case of sporadic adult\u2010onset orthochromatic leucodystrophy associated with pigmented macrophages diagnosed by biopsy without harbouring mutations in the known targeted genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>A 51\u2010year\u2010old woman, with no familial history of neurological diseases, developed a progressive neurological deterioration showing inappropriate behaviour, ataxia, spasticity, axial dystonia and agitation. Radiological images and a stereotaxic biopsy were conclusive with adult\u2010onset orthochromatic leucodystrophy associated with pigmented macrophages. Genetic analysis did not show mutations in either <jats:italic><jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content>1R<\/jats:italic>,<jats:italic> <jats:styled-content style=\"fixed-case\">DAP<\/jats:styled-content>12<\/jats:italic> or <jats:italic><jats:styled-content style=\"fixed-case\">TREM<\/jats:styled-content>2<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We add support to the idea that all these entities are closely related diseases linked to a convergent metabolic pathway, but caused by different genes or perhaps by the combination of individually non\u2010pathogenic variations of selected genes. Genetic defects are still barely known in a substantial number of adult leucodystrophies.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.12741","type":"journal-article","created":{"date-parts":[[2015,5,27]],"date-time":"2015-05-27T14:48:26Z","timestamp":1432738106000},"page":"308-312","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Sporadic adult\u2010onset leucodystrophy with axonal spheroids and pigmented glia with no mutations in the known targeted genes"],"prefix":"10.1111","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3141-6493","authenticated-orcid":false,"given":"Ivan","family":"Fern\u00e1ndez\u2010Vega","sequence":"first","affiliation":[{"name":"Pathology Department of Hospital Universitario Araba \u00c1lava Spain"},{"name":"Brain Bank Hospital Universitario Araba Biobanco Vasco para la Investigaci\u00f3n (O+eHun) Vitoria Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katti","family":"P\u00e9rez de Heredia\u2010Go\u00f1i","sequence":"additional","affiliation":[{"name":"Brain Bank Hospital Universitario Araba Biobanco Vasco para la Investigaci\u00f3n (O+eHun) Vitoria Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge","family":"Santos\u2010Juanes","sequence":"additional","affiliation":[{"name":"Pathology Department Hospital Universitario Central de Asturias Asturias Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel","family":"Go\u00f1i Imizcoz","sequence":"additional","affiliation":[{"name":"Neurology Department Hospital Divino Vall\u00e9s Burgos Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Zaldumbide","sequence":"additional","affiliation":[{"name":"Pathology Department of Hospital Universitario de Cruces Bizkaia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan Jose","family":"Zarranz","sequence":"additional","affiliation":[{"name":"Neurology Department Hospital Universitario de Cruces Bizkaia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isidro","family":"Ferrer","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology Bellvitge University Hospital University of Barcelona Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,7,6]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"254","article-title":"Ludo van Bogaert (1897\u20131989)","volume":"96","author":"Martin L","year":"1996","journal-title":"Acta Neurol. 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