{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T03:19:50Z","timestamp":1777087190494,"version":"3.51.4"},"reference-count":17,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T00:00:00Z","timestamp":1667952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>This study aimed to describe the clinical and radiological characteristics of a cerebello-brainstem dominant form of X-linked adrenoleukodystrophy (X-ALD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Three affected members from a family with cerebellar ataxia received full neurological, laboratory and radiological examinations. Genetic diagnoses were confirmed using whole-exome sequencing and protein structural modeling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All affected members presented with slurred speech, ataxia, and spasticity, but showed obvious differences in phenotypic severity and radiological findings. The levels of very long-chain fatty acids (VLCFA) were elevated in each member, while only one had adrenal dysfunction. Genetic analysis identified a hemizygous missense mutation (c.887A&amp;gt;G, p.Tyr296Cys) of the ATP-binding cassette subfamily D member 1 gene (<jats:italic>ABCD1<\/jats:italic>) in all affected members, which is likely to destabilize the overall structure of the ABCD1 protein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We report a cerebello-dominant form of X-ALD caused by a missense variant in <jats:italic>ABCD1<\/jats:italic>. This report highlights intrafamilial phenotypic variability in X-ALD.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2022.999419","type":"journal-article","created":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T08:33:05Z","timestamp":1667982785000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Cerebello-brainstem dominant form of X-linked adrenoleukodystrophy with intrafamilial phenotypic variability"],"prefix":"10.3389","volume":"13","author":[{"given":"Jae-Hwan","family":"Choi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyun Sung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun Hye","family":"Oh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae Hyeok","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chong Kun","family":"Cheon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,9]]},"reference":[{"key":"B1","article-title":"X-Linked adrenoleukodystrophy","volume-title":"GeneReviews","author":"Raymond","year":"1999"},{"key":"B2","doi-asserted-by":"publisher","first-page":"694","DOI":"10.2174\/138945011795378577","article-title":"subfamily D proteins and very long chain fatty acid metabolism as novel targets in adrenoleukodystrophy","volume":"12","author":"Morita","year":"2011","journal-title":"Curr Drug Targets."},{"key":"B3","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1111\/neup.12230","article-title":"Adult-onset cerebello-brainstem dominant form of X-linked adrenoleukodystrophy presenting as multiple system atrophy: case report and literature review","volume":"36","author":"Ogaki","year":"2016","journal-title":"Neuropathology."},{"key":"B4","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.jns.2009.12.002","article-title":"Spinocerebellar variant of adrenoleukodystrophy with a novel ABCD1 gene mutation","volume":"290","author":"Li","year":"2010","journal-title":"J Neurol Sci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1212\/01.wnl.0000191329.34585.15","article-title":"Progression of the olivopontocerebellar form of adrenoleukodystrophy as shown by MRI","volume":"66","author":"Suda","year":"2006","journal-title":"Neurology."},{"key":"B6","doi-asserted-by":"publisher","first-page":"912","DOI":"10.1111\/j.1468-1331.2005.01134.x","article-title":"X-linked adrenoleukodystrophy with olivopontocerebellar atrophy","volume":"12","author":"Vianello","year":"2005","journal-title":"Eur J Neurol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/S0303-8467(99)00028-1","article-title":"X-linked adrenoleukodystrophy: spinocerebellar variant","volume":"101","author":"Tan","year":"1999","journal-title":"Clin Neurol Neurosurg."},{"key":"B8","doi-asserted-by":"publisher","first-page":"271","DOI":"10.3389\/fneur.2018.00271","article-title":"Novel variant in ABCD1 gene presenting as adolescent-onset atypical adrenomyeloneuropathy with spastic ataxia","volume":"9","author":"Chen","year":"2018","journal-title":"Front Neurol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1007\/BF00685361","article-title":"Adrenoleukodystrophy-cerebello-brainstem dominant case","volume":"60","author":"Kuroda","year":"1983","journal-title":"Acta Neuropathol."},{"key":"B10","first-page":"53","article-title":"An adult case of adrenoleukodystrophy with features of olivo-ponto-cerebellar atrophy: I. 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