title: Spongiform encephalopathy in siblings with no evidence of protease-resistant prion protein or a mutation in the prion protein gene.
abstract: We discuss relevant aspects in two siblings with a neurodegenerative process of unclear aetiology who developed progressive dementia with global aphasia and hyperoral behaviour at the ages of 39 and 46 years and who died 6 and 5 years after disease onset. The cases were reported to the National Reference Center for TSE Surveillance in Göttingen, Germany. Detailed clinical examinations, CSF, blood samples, and copies of the important diagnostic tests (magnetic resonance imaging, electroencephalogram, laboratory tests) were obtained. Further neuropathological and genetic analyses were performed. Cerebral magnetic resonance imaging of both siblings showed prominent changes in signal intensity, especially in the left medial temporal cortex, but also the hippocampal formation. Neuropathological examination revealed spongiform changes, neuronal loss, and astrocytic gliosis, which are typical in Creutzfeldt-Jakob disease. However, no prion protein deposits were detectable by immunohistochemical analysis, Western blot, or PET blot, though abundant tau protein deposits were observed. A mutation in the coding region of the prion protein genes of both siblings was excluded. A detailed search of the literature revealed no other cases with a similar clinical and neuropathological appearance. While the disease aetiology remains unclear, the findings point to a neurodegenerative process and most likely a genetic disease.
authors.affiliation: National Reference Center for TSE Surveillance, Department of Neurology, University Medical Center Göttingen, Robert-Koch Str. 40, 37075 Göttingen, Germany. d.varges@med.uni-goettingen.de
authors.forename: Daniela
authors.initials: D
authors.lastname: Varges
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Schulz-Schaeffer
authors.forename: Wiebke M
authors.initials: WM
authors.lastname: Wemheuer
authors.forename: Insa
authors.initials: I
authors.lastname: Damman
authors.forename: Matthias
authors.initials: M
authors.lastname: Schmitz
authors.forename: Maria
authors.initials: M
authors.lastname: Cramm
authors.forename: Kai
authors.initials: K
authors.lastname: Kallenberg
authors.forename: Katayoon
authors.initials: K
authors.lastname: Shirneshan
authors.forename: Manar
authors.initials: M
authors.lastname: Elkenani
authors.forename: Susanne
authors.initials: S
authors.lastname: Markwort
authors.forename: Michael
authors.initials: M
authors.lastname: Faist
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kohlhase
authors.forename: Otto
authors.initials: O
authors.lastname: Windl
authors.forename: Inga
authors.initials: I
authors.lastname: Zerr
mesh_terms: D000328:Adult; D001037:Aphasia / Q000235:genetics / Q000473:pathology*; D003704:Dementia / Q000235:genetics / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000473:pathology*; D017096:Prion Diseases / Q000235:genetics / Q000473:pathology*; D035781:Siblings
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