Clinical and genetic studies of fatal familial insomnia.
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.
Reder
A T
AT
Department of Neurology, University of Chicago School of Medicine, IL, USA.
Mednick
A S
AS
Brown
P
P
Spire
J P
JP
Van Cauter
E
E
Wollmann
R L
RL
Cervenàkovà
L
L
Goldfarb
L G
LG
Garay
A
A
Ovsiew
F
F
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
D006728:Hormones; D011328:Prions