The
transmissible spongiform encephalopathies or
prion diseases represent a new group of diseases with unique clinical and neuropathological features, the transmission of which is both genetic and infectious. The responsible agent is unconventional and appears to be largely composed of a
glycoprotein, the
prion protein PrP. This is normally present on different cells. In
prion diseases, it becomes converted to the pathogenic form PrPres which is resistant to
proteinase and accumulates within the brain and this process is accompanied by the development of spongiform change,
gliosis and neuronal loss. The human
prion diseases include
Kuru a progressive cerebellar degeneration with late
dementia affecting Fore tribes in New-Guinea, now almost extinct, regarded as being related to cannibalism.
Creutzfeldt-Jakob disease is the more frequent human
prion disease. Its incidence is approximately one case per million per year. Four variants are now recognized: sporadic, familial, iatrogenic and the new variant. The latter represents a distinct clinico-pathological entity. It is now widely accepted that it is due to the same agent responsible for
Bovine Spongiform Encephalopathy in cattle. Gerstmann-Sträussler-Scheinker disease is a very rare inherited disorder due to a number of different mutations in the PRP gene, characterized by abundant deposits of plaque PrPres in the cerebral grey matter.
Fatal familial insomnia is another inherited disorder due to a mutation at
codon 178 of the PRP gene associated with
methionine on
codon 129 of the mutant allele. The main neuropathological change is neuronal loss in the thalamus with little or no spongiosis and usually no PrPres deposition. Following the emergence of new variant CJD in 1996, surveillance of all forms of
prion diseases has been now been actively introduced in many European nations in order to determine the true incidence and geographic distribution of these rare disorders in humans.