Table 1

 Classification of human prion disease

AetiologyPhenotypeFrequency
Sporadic
    Unknown: random distribution worldwide;Sporadic CJD: sub-acute myoclonic form and range of atypical∼85%
    incidence of 1–2 per million per annumforms; multiple distinct prion strains associated with distinct
clinicopathological phenotypes which include sporadic fatal insomnia
Inherited
    Autosomal dominantly inherited conditionsExtremely variable: readily mimics familial Alzheimer’s disease and∼10–15%
    with high penetrance; all forms haveother neurodegenerative conditions; over 30 mutations identified;
    germline PRNP coding mutationsincludes GSS, familial CJD. and fatal familial insomnia
Acquired
    Iatrogenic infection with human prionsIatrogenic CJD: typical CJD when direct central nervous system<5% (most from USA, UK, France,
    via medical or surgical procedures: human(CNS) exposure; ataxic onset when peripheral infectionand Japan)
    cadaveric derived pituitary hormones, tissue
    grafts, and contaminated neurosurgical
    instruments
    Exposure to human prions via endocannibalismKuruUnique to small area of Papua New Guinea; major epidemic in 1950s
with gradual decline since cessation
of cannibalism
    Environmental exposure (presumed
    dietary) to BSE prion strain; probable secondary
    transmission via blood transfusionVariant CJDMainly UK (total to date ∼150), 7 in France, individual patients in several other countries