{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T08:14:20Z","timestamp":1783498460084,"version":"3.55.0"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>AARS2<\/jats:italic>\n                      -related leukoencephalopathy is a rare autosomal recessive leukodystrophy with overlapping clinical and radiological features with CSF1R-related disease but distinct genetic and phenotypic characteristics. Since its description in 2014, fewer than 60 cases have been reported.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted a multicentre retrospective case series of individuals with genetically confirmed\n                      <jats:italic>AARS2<\/jats:italic>\n                      -related leukoencephalopathy, integrating clinical, radiological, and molecular data from 15 newly identified patients. Neuroimaging was reviewed by experienced neuroradiologists, and variants were classified using ACMG criteria. A systematic literature review identified 56 additional cases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Across 71 individuals, mean age at onset was 27.3\u00a0years (range 0\u201357), with balanced sex distribution. Psychiatric and cognitive symptoms predominated early, affecting 70% and 86% of patients. Pyramidal signs (82%), gait disturbance (80%), and extrapyramidal motor features (45%) were common, whilst seizures occurred in 10%. Premature ovarian failure was reported in 82% of females. Sixteen individuals (22.5%) had childhood onset. Neuroimaging showed confluent frontoparietal white matter abnormalities, corpus callosum thinning, and multifocal diffusion abnormalities. Seventy-two unique\n                      <jats:italic>AARS2<\/jats:italic>\n                      variants were identified, including seven novel variants. Missense variants predominated. Notably, variants previously linked only to infantile cardiomyopathy, including p.Arg592Trp, were observed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      <jats:italic>AARS2<\/jats:italic>\n                      -related leukoencephalopathy is clinically and genetically heterogeneous with characteristic imaging and broad onset. Recognition of defining features is essential for diagnosis, and genomic testing should be prioritised. This study provides the most comprehensive characterisation to date and suggests genotype\u2013phenotype separation between cardiomyopathy- and leukodystrophy-associated variants may not be absolute.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00415-026-13964-1","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T15:20:26Z","timestamp":1782487226000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The clinical, radiological and genetic spectrum AARS2-related leukoencephalopathy: a case series of 15 patients and review of the literature"],"prefix":"10.1007","volume":"273","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5199-7566","authenticated-orcid":false,"given":"Charles","family":"Wade","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anderson Rodrigues Brand\u00e3o","family":"de Paiva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo Ribeiro","family":"N\u00f3brega","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana C Andorinho","family":"de Freitas Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana C Martins","family":"Borges","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lecio Figueira","family":"Pinto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Brand\u00e3o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro Maia Nobre Rocha","family":"Saffi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz Felipe","family":"Vasconcellos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah Moreira","family":"Rangel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula Camila A. 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