{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:00:19Z","timestamp":1791406819163,"version":"4.3.3"},"reference-count":28,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Very long chain fatty acids (VLCFAs) are an integral component of myelin and the epidermal water barrier. Variants in genes encoding enzymes responsible for catalyzing the first and rate limiting step in the production of VLCFAs, elongation of VLCFAs (ELOVLs), underlie a novel group of metabolic disorders.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The goal was to describe the clinical phenotype and disturbance in VLCFA metabolism associated with variants in the <jats:italic>ELOV1<\/jats:italic> gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The following methods were employed: Exome sequencing, clinical phenotyping, magnetic resonance imaging (MRI), metabolomics, liquid chromatography\u2013tandem mass spectrometry, fatty acid elongation assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We, here, describe seven patients with autosomal recessive variants in <jats:italic>ELOVL1<\/jats:italic>. Common clinical features included ichthyosis (5\/7), developmental delay (7\/7), progressive spasticity (7\/7), nystagmus (5\/6), and a complex movement disorder characterized by pronounced head tremor (7\/7), myoclonus (6\/7), and dysarthria (6\/6). Brain MRI revealed non\u2010progressive hypomyelination (6\/6) and hypoplasia of the corpus callosum (5\/6). Plasma VLCFA analysis in one patient showed reduced concentrations of C24:0 and C26:0. Biochemical analysis of fibroblasts from this patient revealed elongation defects in VLCFA synthesis and dysregulation of other ELOVL enzymes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We show that biallelic variants in <jats:italic>ELOVL1<\/jats:italic> are associated with a unique and recognizable phenotype of hypomyelinating leukodystrophy, ichthyosis, and a complex movement disorder including progressive spasticity, head tremor, and myoclonus. Biochemical analyses confirmed a defect in VLCFA synthesis. Variants in genes encoding enzymes involved in the elongation of VLCFAs are a novel group of metabolic disorders with overlapping symptoms. \u00a9 2025 The Author(s). <jats:italic>Movement Disorders<\/jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.30258","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T09:10:01Z","timestamp":1751361001000},"page":"1836-1850","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Biallelic <scp><i>ELOVL1<\/i><\/scp> Variants Are Linked to Hypomyelinating Leukodystrophy, Movement Disorder, and Ichthyosis"],"prefix":"10.1002","volume":"40","author":[{"given":"Keit Men","family":"Wong","sequence":"first","affiliation":[{"name":"Department of Neuropediatrics Jena University Hospital  Jena Germany"},{"name":"Center for Rare Diseases Jena University Hospital  Jena Germany"},{"name":"School of Pharmacy, University of Wyoming  Laramie Wyoming USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Maroofian","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases Queen Square, Institute of Neurology, University College London  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kolja","family":"Meier","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Pediatric Neurology and German Center for Child and Adolescent Health (DZKJ) University Medical Center G\u00f6ttingen, Georg August University G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susann","family":"Diegmann","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Pediatric Neurology and German Center for Child and Adolescent Health (DZKJ) University Medical Center G\u00f6ttingen, Georg August University G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tinatin","family":"Tkemaladze","sequence":"additional","affiliation":[{"name":"Division of Clinical Genetics Givi Zhvania Pediatric University Clinic, Tbilisi State Medical University  Tiblisi Georgia"},{"name":"Department of Molecular and Medical Genetics Tbilisi State Medical University  Tbilisi Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javeria Raza","family":"Alvi","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Children's Hospital and Institute of Child Health  Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Behnoosh","family":"Tasharrofi","sequence":"additional","affiliation":[{"name":"Watson Genetic Laboratory  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Efthymiou","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases Queen Square, Institute of Neurology, University College London  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3219-2284","authenticated-orcid":false,"given":"Alexander","family":"Munchau","sequence":"additional","affiliation":[{"name":"Institute of Systems Motor Science and Center for Rare Diseases University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. Christoph","family":"Korenke","sequence":"additional","affiliation":[{"name":"Section of Neonatology and Pediatric Intensive Care, Department of Pediatrics School VI\u2010School of Medicine and Health Sciences, Carl von Ossietzky Universit\u00e4t Oldenburg  Oldenburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naif","family":"Almontashiri","sequence":"additional","affiliation":[{"name":"College of Applied Medical Sciences and Center for Genetics and Inherited Diseases Taibah University  Madinah Kingdom of Saudi Arabia"},{"name":"Research Department King Khaled Eye Specialist Hospital  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wafaa","family":"Eyaid","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and Precision Medicine King Abdulaziz Medical City  Riyadh Kingdom of Saudi Arabia"},{"name":"Department of Medical Genomics King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences  Riyadh Kingdom of Saudi Arabia"},{"name":"College of Medicine, King Saud Bin Abdulaziz University for Health Sciences  Riyadh Kingdom of Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amna","family":"Kashgari","sequence":"additional","affiliation":[{"name":"College of Medicine, King Saud Bin Abdulaziz University for Health Sciences  Riyadh Kingdom of Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Modhi","family":"Alotaibi","sequence":"additional","affiliation":[{"name":"Department of Biology College of Science, Princess Nourah bint Abdulrahman University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jutta","family":"G\u00e4rtner","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Pediatric Neurology and German Center for Child and Adolescent Health (DZKJ) University Medical Center G\u00f6ttingen, Georg August University G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda","family":"Huppke","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics Jena University Hospital  Jena Germany"},{"name":"Center for Rare Diseases Jena University Hospital  Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mostafa","family":"Asadollahi","sequence":"additional","affiliation":[{"name":"Watson Genetic Laboratory  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gocha","family":"Chikvinidze","sequence":"additional","affiliation":[{"name":"Department of Child Neurology I. 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