Prion disease is a group of progressive conditions that affect the brain and nervous system of humans and animals. In people, these disorders impair brain function, causing memory changes, personality changes, and problems with movement that worsen over time. The signs and symptoms of prion disease typically begin in adulthood, and the course of these disorders ranges from a few months to several years.

Familial prion diseases of humans include classic Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome, and fatal insomnia. These conditions form a spectrum of diseases with overlapping signs and symptoms.

These disorders are very rare. They affect about one person per million worldwide each year. Approximately 300 cases occur annually in the United States.

Mutations in the PRNP gene cause prion disease.

Familial forms of prion disease are caused by inherited mutations in the PRNP gene; however, only a small percentage of cases run in families. Most cases are sporadic, which means they occur in people without any known risk factors or gene mutations. Rarely, prion diseases can be transmitted by exposure to prion-contaminated tissues or other biological materials from affected individuals. This type of prion disease is described as iatrogenic.

One type of prion disease in humans, variant Creutzfeldt-Jakob disease (vCJD), is acquired by eating beef products obtained from affected cattle. (In cows, this form of prion disease is known as bovine spongiform encephalopathy, BSE, or, more commonly, "mad cow" disease). Another example of an acquired prion disease is kuru, which was identified in the South Fore tribe in Papua New Guinea. The disorder was transmitted when tribe members ate the tissue of affected people during cannibalistic funeral rituals.

The PRNP gene provides instructions for making a protein called a prion protein (PrP). Normally, this protein seems to be involved in transporting copper into cells. It may also play a role in protecting brain cells and helping them communicate. In familial cases of prion disease, mutations in the PRNP gene cause cells to produce an abnormal form of the prion protein known as PrP^Sc. In iatrogenic and acquired cases, an affected person develops prion disease from exposure to this abnormal protein.

In a process that is not fully understood, PrP^Sc has the ability to convert the normal prion protein, PrP^C, into PrP^Sc. This abnormal protein builds up in the brain, forming clumps that damage or destroy nerve cells. The loss of these cells creates microscopic sponge-like holes in the brain, which leads to the signs and symptoms of prion disease.

Familial forms of prion disease are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the altered gene from one affected parent. In some people, familial forms of prion disease are caused by a new mutation in the PRNP gene. Although such people most likely do not have an affected parent, they can pass the genetic change to their children.

The sporadic, iatrogenic, and acquired forms of prion disease, including kuru and variant Creutzfeldt-Jakob disease, are not inherited.