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Jacoby Professorship for Alzheimer's Disease Research and NIH"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:p>X\u2010linked adrenoleukodystrophy (X\u2010ALD) is the most common peroxisomal disorder and is caused by <jats:italic>ABCD1<\/jats:italic> mutations. A cerebello\u2010brainstem dominant form that mainly involves the cerebellum and brainstem is summarized in a review of the literature, with autopsy\u2010confirmed cases exceedingly rare. We report a 69\u2010year\u2010old White man who was diagnosed with this rare disorder and describe neuropathologic, ultrastructural and genetic analyses. He did not have adrenal insufficiency or a family history of X\u2010ALD or Addison's disease. His initial symptom was temporary loss of eyesight at age 34\u2009years. His major symptoms were chronic and progressive gait disorder, weakness in his lower extremities and spasticity, as well as autonomic failure and cerebellar ataxia suggesting possible multiple system atrophy (MSA). He also had seizures, hearing loss and sensory disturbances. His brain MRI showed no obvious atrophy or significant white matter pathology in cerebrum, brainstem or cerebellum. He died at age 69\u2009years with a diagnosis of MSA. Microscopic analysis showed mild, patchy myelin rarefaction with perivascular clusters of PAS\u2010positive, CD68\u2010positive macrophages in the white matter most prominent in the cerebellum and occipital lobe, but also affecting the optic tract and internal capsule. Electron microscopy of cerebellar white matter showed cleft\u2010like trilamellar cytoplasmic inclusions in macrophages typical of X\u2010ALD, which prompted genetic analysis that revealed a novel <jats:italic>ABCD1<\/jats:italic> mutation, p.R163G. Given the relatively mild pathological findings and long disease duration, it is likely that the observed pathology was the result of a slow and indolent disease process. We described a patient who had sporadic cerebello\u2010brainstem dominant form of X\u2010ALD with long clinical course, mild pathological findings, and an <jats:italic>ABCD1<\/jats:italic> p.R163G substitution. We also review a total of 34 cases of adult\u2010onset cerebello\u2010brainstem dominant form of X\u2010ALD. Although rare, X\u2010ALD should be considered in the differential diagnosis of MSA.<\/jats:p>","DOI":"10.1111\/neup.12230","type":"journal-article","created":{"date-parts":[[2015,7,31]],"date-time":"2015-07-31T08:12:24Z","timestamp":1438330344000},"page":"64-76","source":"Crossref","is-referenced-by-count":30,"title":["Adult\u2010onset cerebello\u2010brainstem dominant form of X\u2010linked adrenoleukodystrophy presenting as multiple system atrophy: case report and literature review"],"prefix":"10.1111","volume":"36","author":[{"given":"Kotaro","family":"Ogaki","sequence":"first","affiliation":[{"name":"Department of Neuroscience Mayo Clinic  Jacksonville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunsuke","family":"Koga","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Mayo Clinic  Jacksonville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoya","family":"Aoki","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Mayo Clinic  Jacksonville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenlang","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Mayo Clinic  Jacksonville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinuko","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Neuropathology Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology  Tokyo Japan"},{"name":"Department of Pathology and Laboratory Medicine University of North Carolina at Chapel Hill  NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Owen A.","family":"Ross","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Mayo Clinic  Jacksonville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis W.","family":"Dickson","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Mayo Clinic  Jacksonville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,7,31]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/120.8.1485"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.1227"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00312873"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.27.12.1107"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.27.12.1114"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2010.00390.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2012.03.012"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00343796"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00685361"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.32.9.1031"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00867585"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-8467(99)00028-1"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0900688106"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg509"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2890"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1974.00490390092013"},{"key":"e_1_2_7_19_1","first-page":"643","volume-title":"Greenfield's Neuropathology","author":"Powers JM","year":"2009"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000324625.00404.15"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70288-1"},{"key":"e_1_2_7_22_1","first-page":"53","article-title":"An adult case of adrenoleukodystrophy with features of olivo\u2010ponto\u2010cerebellar atrophy: I. 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