title: A subtype of sporadic prion disease mimicking fatal familial insomnia.
abstract: OBJECTIVE
  To establish a variant of sporadic prion disease as the sporadic form of fatal familial insomnia (FFI).
  
  
  BACKGROUND
  FFI is a recently described prion disease characterized clinically by severe sleep impairment, dysautonomia, and motor signs, and pathologically by atrophy of thalamic nuclei, especially the medial dorsal and anterior ventral, and of the inferior olive. FFI is linked to the D178N mutation coupled with the methionine codon at position 129 in the prion protein gene (PRNP). It is also identified by the properties of the abnormal prion protein (PrP(Sc)), which has the relative molecular mass of 19 kDa, corresponding to the so-called type 2, and a marked underrepresentation of the unglycosylated form relative to the diglycosylated and monoglycosylated forms.
  
  
  METHODS
  Clinical, pathologic, PrP(Sc), and PRNP data from 5 subjects with a sporadic prion disease phenotypically similar to FFI were collected and analyzed.
  
  
  RESULTS
  All 5 subjects had a disease clinically similar and histopathologically virtually identical to FFI. PrP(Sc) type 2 was present in all subjects in amount and distribution similar to those of FFI. However, the PrP(Sc) did not show the striking underrepresentation of the unglycosylated isoform of the protein that is characteristic of FFI. Moreover, none of the subjects had the D178N PRNP mutation but all were homozygous for methionine at codon 129.
  
  
  CONCLUSIONS
  This condition is likely to represent the sporadic form of FFI and the term "sporadic fatal insomnia" is proposed.
authors.affiliation: Division of Neuropathology, Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: P
authors.initials: P
authors.lastname: Parchi
authors.forename: S
authors.initials: S
authors.lastname: Capellari
authors.forename: S
authors.initials: S
authors.lastname: Chin
authors.forename: H B
authors.initials: HB
authors.lastname: Schwarz
authors.forename: N P
authors.initials: NP
authors.lastname: Schecter
authors.forename: J D
authors.initials: JD
authors.lastname: Butts
authors.forename: P
authors.initials: P
authors.lastname: Hudkins
authors.forename: D K
authors.initials: DK
authors.lastname: Burns
authors.forename: J M
authors.initials: JM
authors.lastname: Powers
authors.forename: P
authors.initials: P
authors.lastname: Gambetti
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D017096:Prion Diseases / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology