title: Clinical and genetic studies of fatal familial insomnia.
abstract: We report a 42-year-old man who, for 8 months, had intermittent motor abnormalities and mild difficulty falling asleep. A diagnosis of fatal familial insomnia (FFI) became evident over the next 6 months when he developed progressive insomnia, myoclonus, sympathetic hyperactivity, and dementia. The amyloid or prion protein (PrP) genotype showed features typically seen in FFI, with a 178Asn mutation and a 129Met polymorphism. There was also a deletion of one octapeptide repeat, suggesting that the association of 178Asn mutation with the 129Met polymorphism is not due to "founder effect." Western immunoblot showed a trace of protease-resistant PrP in the thalamus--which had the most significant neuronal loss and gliosis--a moderate amount of PrP in the fronto-temporal area, and no detectable protein elsewhere in the brain. Endocrine studies showed that a circadian modulation of hormonal levels could be maintained despite a near-total absence of sleep. Administration of gamma-hydroxybutyrate induced a remarkable increase in slow-wave sleep.
authors.affiliation: Department of Neurology, University of Chicago School of Medicine, IL, USA.
authors.forename: A T
authors.initials: AT
authors.lastname: Reder
authors.forename: A S
authors.initials: AS
authors.lastname: Mednick
authors.forename: P
authors.initials: P
authors.lastname: Brown
authors.forename: J P
authors.initials: JP
authors.lastname: Spire
authors.forename: E
authors.initials: E
authors.lastname: Van Cauter
authors.forename: R L
authors.initials: RL
authors.lastname: Wollmann
authors.forename: L
authors.initials: L
authors.lastname: Cervenàkovà
authors.forename: L G
authors.initials: LG
authors.lastname: Goldfarb
authors.forename: A
authors.initials: A
authors.lastname: Garay
authors.forename: F
authors.initials: F
authors.lastname: Ovsiew
mesh_terms: D000328:Adult; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D017809:Fatal Outcome; D006728:Hormones / Q000378:metabolism; D006801:Humans; D008297:Male; D009154:Mutation; D011328:Prions / Q000235:genetics; D007319:Sleep Initiation and Maintenance Disorders / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy
chemical_list: D006728:Hormones; D011328:Prions