title: Two autopsy cases with Pelizaeus-Merzbacher disease phenotype of adult onset, without mutation of proteolipid protein gene.
abstract: We report the autopsy cases of two brothers which are pathologically compatible with Pelizaeus-Merzbacher disease (PMD). Both patients had a late onset (at the ages of 29 and 42 years) and chronic neurological symptoms including tremor, ataxia and dementia. The T2-weighted magnetic resonance imaging of the younger brother demonstrated increased signal areas with sparing of small areas in the cerebral white matter. The postmortem examinations, obtained at the ages of 45 and 61 years, showed similar neuropathological findings. Histologically, a cardinal finding was a lack of myelin in large parts of white matter with the preservation of islands of intact myelin, resulting in a "tigroid" appearance. Only small amounts of sudanophilic material were present. The axons were relatively well preserved, but oligodendrocytes were numerically reduced. Ultrastructurally, myelin sheaths in the white matter were markedly thin. Immunohistochemistry showed that proteolipid protein (PLP) was reduced in the affected white matter. However, genetic studies did not reveal exonic mutations or duplications of the PLP gene. We conclude that the two cases are a rare type of dysmyelinating disorder with PMD phenotype of adult onset and could be caused by previously unrecognized abnormalities of the PLP gene or other genes.
authors.affiliation: Department of Pathology, Gunma University School of Medicine, Maebashi, Japan. achie@news.sb.gunma-u.ac.jp
authors.forename: A
authors.initials: A
authors.lastname: Sasaki
authors.forename: K
authors.initials: K
authors.lastname: Miyanaga
authors.forename: M
authors.initials: M
authors.lastname: Ototsuji
authors.forename: A
authors.initials: A
authors.lastname: Iwaki
authors.forename: T
authors.initials: T
authors.lastname: Iwaki
authors.forename: S
authors.initials: S
authors.lastname: Takahashi
authors.forename: Y
authors.initials: Y
authors.lastname: Nakazato
mesh_terms: D000328:Adult; D017668:Age of Onset; D001921:Brain / Q000378:metabolism / Q000473:pathology; D017809:Fatal Outcome; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D018991:Myelin Proteolipid Protein / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D020371:Pelizaeus-Merzbacher Disease / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D010641:Phenotype
chemical_list: D018991:Myelin Proteolipid Protein