new variant Creutzfeldt-Jakob disease

Last reviewed 01/2018

Variant Creutzfeldt-Jakob disease (vCJD) is a novel human prion disease caused by the bovine spongiform encephalopathy agent

• most cases have occurred in the UK, with smaller numbers in 11 other countries
• all definite vCJD cases have occurred in methionine homozygotes at codon 129 in the prion protein gene
• following oral infection, the vCJD agent appears to replicate in lymphoid tissues during the asymptomatic phase of the incubation period

Variant CJD resulting from the human transmission of BSE mainly through dietary exposure, has steadily declined in incidence in the UK since 2000, with a total 176 cases (1)

• the prevalence of subclinical infection indicated by anonymous surveys of appendiceal tissue, remains a significant concern at around 1:2000 in the UK (http://www.hpa.org.uk/hpr/archives/2012/news3212.htm#bnrmlprn)
  • subclinically infected individuals may never convert to clinical cases, however they pose risks for iatrogenic transmission by blood or blood product transfusion, by dentistry and surgery.

Notes:

• vCJDis one of the transmissible spongiform encephalopathies, which affect humans and other mammals
  • these neurodegenerative conditions, also known as prion diseases, are potentially transmissible, although most human diseases are apparently not acquired
    • share a common molecular abnormality: a post-translational conformational change in a normal host protein (the prion protein, encoded in humans by the prion protein (PRNP) gene on chromosome 20)
    • transmissibility necessitates an infectious agent that has been termed the 'prion'
      • according to the prion hypothesis, the prion consists entirely or mainly of the abnormally folded prion protein (designated PrPSc, the normal form being designated PrPc). The abnormal prion protein appears to cause a cascade of misfolding in the normal cellular prion, similarly altering its conformational structure and propagating the disease.

Reference:

• Ironside J.W. Variant Creutzfeldt-Jakob disease: an update. Folia Neuropathol. 2012;50:50-56.
• Mackay GA et al. The molecular epidemiology of variant CJD. Int J Mol Epidemiol Genet. 2011 Aug 30;2(3):217-27.