This autosomal dominant disorder is due to a mutation at codon 178 of the prion protein gene, in which asparagine is substituted for aspartate coupled with the presence of methionine rather than valine at position 129 . This leads to production of an abnormal form of a glycoprotein (prion protein) which is resistant to proteases and leads to neuronal death, particularly in the mediodorsal and anterior thalamic nuclei. Progression of the disease is more rapid in methionine homozygotes than methionine-valine heterozygotes.
This condition is equally common in males and females. It is usually familial but occasionally sporadic, and usually appears between the ages of 40 and 70 years. Progressively worsening insomnia is associated with vivid dreams and motor activity similar to that of the REM sleep behaviour disorder. The fall in total sleep time is associated with disintegration of the sleep structure with no discernible NREM or REM sleep. The normal 24-h rest-activity cycle is lost and the circadian cortisol rhythm disappears. Autonomic and motor abnormalities appear, but cognitive function is retained until stupor and eventually coma develop shortly before death. This usually occurs 6-24 months after the onset of the condition.
The differential diagnosis includes the REM sleep behaviour disorder, although this does not have any autonomic abnormalities, dementia, particularly due to Alzheimer's disease, Creutzfeldt-Jakob disease and occasionally schizophrenia.
There is no effective treatment.
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