{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T15:58:03Z","timestamp":1792166283917,"version":"4.4.0"},"reference-count":41,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,7,9]],"date-time":"2020-07-09T00:00:00Z","timestamp":1594252800000},"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":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Sj\u00f6gren\u2010Larsson syndrome (SLS) is a rare neurometabolic syndrome caused by deficient fatty aldehyde dehydrogenase. Patients exhibit intellectual disability, spastic paraplegia, and ichthyosis. The accumulation of fatty alcohols and fatty aldehydes has been demonstrated in plasma and skin but never in brain. Brain magnetic resonance imaging and spectroscopy studies, however, have shown an abundant lipid peak in the white matter of patients with SLS, suggesting lipid accumulation in the brain as well. Using histopathology, mass spectrometry imaging, and lipidomics, we studied the morphology and the lipidome of a postmortem brain of a 65\u2010year\u2010old female patient with genetically confirmed SLS and compared the results with a matched control brain. Histopathological analyses revealed structural white matter abnormalities with the presence of small lipid droplets, deficient myelin, and astrogliosis. Biochemically, severely disturbed lipid profiles were found in both white and gray matter of the SLS brain, with accumulation of fatty alcohols and ether lipids. Particularly, long\u2010chain unsaturated ether lipid species accumulated, most prominently in white matter. Also, there was a striking accumulation of odd\u2010chain fatty alcohols and odd\u2010chain ether(phospho)lipids. Our results suggest that the central nervous system involvement in SLS is caused by the accumulation of fatty alcohols leading to a disbalance between ether lipid and glycero(phospho)lipid metabolism resulting in a profoundly disrupted brain lipidome. Our data show that SLS is not a pure leukoencephalopathy, but also a gray matter disease. Additionally, the histopathological abnormalities suggest that astrocytes and microglia might play a pivotal role in the underlying disease mechanism, possibly contributing to the impairment of myelin maintenance.<\/jats:p>","DOI":"10.1002\/jimd.12275","type":"journal-article","created":{"date-parts":[[2020,6,18]],"date-time":"2020-06-18T11:35:48Z","timestamp":1592480148000},"page":"1265-1278","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Disturbed brain ether lipid metabolism and histology in\n                    <scp>Sj\u00f6gren\u2010Larsson<\/scp>\n                    syndrome"],"prefix":"10.1002","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0238-1412","authenticated-orcid":false,"given":"Pippa","family":"Staps","sequence":"first","affiliation":[{"name":"Department of Pediatric Neurology, Radboud university medical center, Amalia Children's Hospital, Donders Institute for Brain Cognition and Behaviour  Nijmegen Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William B.","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Child Health Research Institute University of Nebraska Medical Center  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric M.","family":"Vaz","sequence":"additional","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases, Core Facility Metabolomics, Amsterdam UMC, University of Amsterdam Amsterdam Gastroenterology &amp; Metabolism  Amsterdam Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Bugiani","sequence":"additional","affiliation":[{"name":"Department of Pathology VU University Medical Center  Amsterdam Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Giera","sequence":"additional","affiliation":[{"name":"Center for Proteomics &amp; Metabolomics Leiden University Medical Center  Leiden Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bram","family":"Heijs","sequence":"additional","affiliation":[{"name":"Center for Proteomics &amp; Metabolomics Leiden University Medical Center  Leiden Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine H. C.","family":"van Kampen","sequence":"additional","affiliation":[{"name":"Bioinformatics Laboratory, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam Public Health research institute, Amsterdam UMC University of Amsterdam  Netherlands"},{"name":"Biosystems Data Analysis, Swammerdam Institute for Life Sciences University of Amsterdam  Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mia L.","family":"Pras\u2010Raves","sequence":"additional","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases, Core Facility Metabolomics, Amsterdam UMC, University of Amsterdam Amsterdam Gastroenterology &amp; Metabolism  Amsterdam Netherlands"},{"name":"Bioinformatics Laboratory, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam Public Health research institute, Amsterdam UMC University of Amsterdam  Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjolein","family":"Breur","sequence":"additional","affiliation":[{"name":"Department of Pathology VU University Medical Center  Amsterdam Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemieke","family":"Groen","sequence":"additional","affiliation":[{"name":"Department of Pathology VU University Medical Center  Amsterdam Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sacha","family":"Ferdinandusse","sequence":"additional","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases, Core Facility Metabolomics, Amsterdam UMC, University of Amsterdam Amsterdam Gastroenterology &amp; Metabolism  Amsterdam Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marinette","family":"van der Graaf","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine Radboud University Medical Center  Nijmegen Netherlands"},{"name":"Department of Pediatrics, Radboud University Medical Center Amalia Children's Hospital  Nijmegen Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gert","family":"Van Goethem","sequence":"additional","affiliation":[{"name":"Het GielsBos, Gierle, Belgium and Department of Neurology University Hospital of Antwerp (UZA)  Antwerp Belgium"},{"name":"Department of Pathology Antwerp University Hospital, Edegem, and Laboratory of Neuropathology, Born\u2010Bunge Institute University of Antwerp  Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Lammens","sequence":"additional","affiliation":[{"name":"Department of Pathology Antwerp University Hospital, Edegem, and Laboratory of Neuropathology, Born\u2010Bunge Institute University of Antwerp  Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron A.","family":"Wevers","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Translational Metabolic Laboratory Radboud University Medical Center  Nijmegen Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7860-7791","authenticated-orcid":false,"given":"Mich\u00e8l A. 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