Prion diseases are progressive, fatal, and untreatable degenerative brain disorders.
Prominent types include
Creutzfeldt-Jakob disease (CJD), the prototypic example (usually sporadic)
Variant CJD (vCJD; acquired by eating prion-contaminated beef)
Variably protease-sensitive prionopathy (VPSPr; sporadic)
Gerstmann-Sträussler-Scheinker disease (GSS; inherited)
Fatal insomnia (FI; includes a sporadic and an inherited form)
Kuru (acquired by ritual cannibalism)
A recently identified type is prion disease associated with diarrhea and autonomic neuropathy, which is inherited.
Prion diseases result from misfolding of a normal cell-surface brain protein called cellular prion protein (PrPC), whose exact function is unknown. Misfolded prion proteins are called prions or scrapie PrP (PrPSc—from the name of the prototypic prion disease of sheep).
Prions (PrPSc) are pathogenic and often infectious. They produce prion disease by
Normal PrPC is water soluble and protease sensitive, but a large percentage of PrPSc is water insoluble and markedly resistant to protease degradation (similar to beta-amyloid in Alzheimer disease, which PrPSc resembles), resulting in slow but inexorable cellular accumulation and neuronal cell death. Accompanying pathologic changes include gliosis and characteristic histologic vacuolar (spongiform) changes, resulting in dementia and other neurologic deficits. In acquired prion diseases, symptoms and signs develop months to years after the initial exposure to PrPSc.
Prion diseases should be considered in all patients with dementia, especially if it progresses rapidly.
Prion diseases originate
Sporadic prion diseases are the most common, with a worldwide annual incidence of about 1/1 million people. How PrPSc first forms is unknown.
Familial prion diseases are caused by defects in the PrP gene, which is contained in the short arm of chromosome 20. The genetic mutations causing prion diseases are autosomal dominant; ie, they cause disease when they are inherited from only one parent. Also, penetrance is variable; ie, depending on the type of mutation, a variable percentage of carriers of the mutation have clinical signs of the disease during their lifetime.
More than 50 mutations exist. Different gene defects cause different types of prion disease, which include
Familial Creutzfeldt-Jakob disease (CJD)
Gerstmann-Sträussler-Scheinker disease (GSS)
Diseases with mixed features of CJD and GSS
Diseases that are clinically and pathologically different from other prion diseases, such as prion disease associated with diarrhea and autonomic neuropathy
Fatal familial insomnia (FFI)
To date, researchers have identified only one mutation that causes FFI, the familial form of fatal insomnia.
The PrP gene mutations alter the amino acid sequence of PrPC, causing it to misfold and become PrPSc. Small abnormalities in specific codons (nucleotide sequences that are the building blocks of genes), which on their own do not cause disease, may determine the predominant symptoms and rate of disease progression in familial and other prion diseases (1).
Infectiously transmitted prion diseases are rare. They can be transmitted
Prion diseases are not known to be contagious through casual person-to-person contact.
Prion diseases occur in many mammals (eg, mink, elk, deer, domestic sheep and cattle) and can be transmitted between species via the food chain. However, transmission from animals to humans has been observed only in vCJD, after people consumed beef from cattle with bovine spongiform encephalopathy (BSE, or mad cow disease).
In several western US states, Canada, and now South Korea and Norway (2), there is concern that chronic wasting disease (CWD), the prion disease of elk and deer, may be transmissible to people who hunt, butcher, or eat the affected animals. Although transmission of CWD from animals to humans is unlikely, recent data indicate that the barriers between species may be weakened when CWD has been transmitted from animal to animal several times (as may happen in the wild ).
1. Pocchiari M and Manson J, editors. Human Prion Diseases. In Handbook of Clinical Neurology, edited by M Pocchiari, and J Manson. New York, Elsevier, 2018, vol 153, pp. 2–498.
2. Benestad SL, Mitchell G, Simmons M, et al: First case of chronic wasting disease in Europe in a Norwegian free-ranging reindeer. Vet Res 47 (1):88, 2016. doi: 10.1186/s13567-016-0375-4.
3. Barria MA, Telling GC, Gambetti P, et al: Generation of a new form of human PrPSc in vitro by interspecies transmission from cervid prions. J Biol Chem 286 (9):7490–7495, 2011. doi: 10.1074/jbc.M110.198465.
There is no treatment for prion diseases. Treatment is supportive.
Patients should be encouraged to prepare advance directives (eg, preferred end-of-life care) soon after the disorder is diagnosed.
Genetic counseling may be recommended for family members of patients with a familial prion disease.
Prions resist standard disinfection techniques and may be a risk to other patients and to surgeons, pathologists, or technicians who handle contaminated tissues or instruments.
Transmission can be prevented by taking precautions when handling infected tissues and by using appropriate techniques to clean contaminated instruments. Using one of the following procedures is recommended: