title: [The spectrum of prion pathology broadens: fatal familial insomnia].
abstract: BACKGROUND
  The small group of prion diseases, caused by accumulation in the brain of an abnormal protein characterized by its aggregation and relative resistance to proteases (the PrPSc) in man is comprised of Creutzfeldt-Jacob disease (CJE), the Gerstmann-Straussler-Scheinker syndrome, kuru and the newest addition which is fatal familial insomnia (FFI).
  
  
  METHODS
  FFI is a hereditary condition with dominant autosomal transmission, characterized clinically by progressive insomnia, dysautonomy, changes in the circadian rhythm of hormone secretion, motor signs and slight to moderate deterioration of cognition. The usual age of onset is between 40 and 60 years, and the course of the illness lasts between 7 and 18 months. The histopathological changes, involving neurone loss and reactive gliosis, particularly affect the anteroventral and dorsomedial thalamic nuclei. These lesions lead to insomnia and to autonomic and endocrine disorders. To a lesser extent and degree, lesions are seen in other thalamic nuclei, the cerebral cortex, inferior olives and the cerebellum. FFI and some families with CJE have the same mutation of the codon 178 of the protein prion gene (gene PRNP) with substitution of aspartic acid by asparagine. Polymorphism of codon 129, which codifies methionine or valine determines the development of the clinical and neuropathological phenotype of FFI or CJE respectively.
  
  
  CONCLUSIONS
  The description of FFI and the detection of PrPSe in familial cases of diffuse subcortical gliosis has indicated the possibility that there may be other familial or non-familial neurodegenerative diseases caused by prions.
authors.affiliation: Servicio de Neurología, Hospital del Aire, Madrid.
authors.forename: S
authors.initials: S
authors.lastname: Delgado-Reyes
authors.forename: N
authors.initials: N
authors.lastname: Feito-Ibarz
authors.forename: A
authors.initials: A
authors.lastname: Ruiz-Aláez
authors.forename: M L
authors.initials: ML
authors.lastname: García de la Rocha
authors.forename: A
authors.initials: A
authors.lastname: Martín-Araguz
authors.forename: J M
authors.initials: JM
authors.lastname: Moreno-Martínez
mesh_terms: D000328:Adult; D000368:Aged; D002940:Circadian Rhythm / Q000502:physiology; D003062:Codon / Q000235:genetics; D004402:Dysautonomia, Familial / Q000235:genetics; D010450:Endopeptidases / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D018621:PrPC Proteins / Q000235:genetics*; D017096:Prion Diseases / Q000201:enzymology / Q000235:genetics; D007319:Sleep Initiation and Maintenance Disorders / Q000235:genetics* / Q000473:pathology; D013788:Thalamus / Q000473:pathology
chemical_list: D003062:Codon; D018621:PrPC Proteins; D010450:Endopeptidases
vernacular_title: El espectro de la patología prion se amplía: el insomnio familiar fatal.