Fatal familial insomnia

Fatal familial insomnia (FFI) is a very rare autosomal dominant inherited prion disease of the brain. The dominant gene responsible has been found in just 50 families worldwide; if only one parent has the gene, the offspring have a 50% chance of inheriting it and developing the disease. The disease's genesis and the patient's progression into complete sleeplessness is untreatable, and ultimately fatal.

History
Fatal familial insomnia was first detected by Italian doctor Ignazio Roiter in 1974, who discovered two women from one family who apparently died of insomnia. Family records showed a history of seemingly related deaths. Another member of the family fell ill in 1984; the patient's deterioration was studied and after his death his brain was flown to the U.S. for further investigation.

In the late 1990s, researchers discovered that the disease is caused by a dual mutation in a protein called a prion protein (PrP): asparagine-178 replaces aspartic acid while methionine is present at amino acid 129. These mutations result in the formation of an insoluble prion protein, termed PrPsc.

Pathophysiology
PrPsc has autocatalytic properties that cause normally soluble PrP to be converted into the PrPsc form upon interaction.

This conversion into insoluble protein causes plaques containing aggregates of PrPsc to develop in the thalamus, a region of the brain responsible for regulation of sleep. This first results in insomnia, and then progresses to more serious problems over time.

Presentation
The age of onset is variable, ranging from 30 to 60, with an average of 50. However the disease tends to prominently occur in later years, primarily following childbirth. Death usually occurs between 7 to 36 months from onset. The presentation of the disease varies considerably from person to person, even among patients from within the same family.

The disease has four stages, taking 7 to 18 months to run its course:


 * 1) The patient suffers increasing insomnia, resulting in panic attacks, paranoia, and phobias. This stage lasts for about four months.
 * 2) Hallucinations and panic attacks become noticeable, continuing for about five months.
 * 3) Complete inability to sleep is followed by rapid loss of weight. This lasts for about three months.
 * 4) Dementia, during which the patient becomes unresponsive or mute over the course of six months. This is the final progression of the disease, and the patient will subsequently die.

Treatment
There is no cure or treatment for FFI; hope rests on the so far unsuccessful gene therapy. Sleeping pills have no helpful effect, but, in fact, make the situation much worse.

While it is not currently possible to reverse the underlying illness, there is some evidence that treatments that focus upon the symptoms can improve quality of life.

Related conditions
There are other diseases involving the mammalian prion. Some are transmissible (TSEs) such as kuru, bovine spongiform encephalopathy (BSE, also known as "mad cow disease") in cows, and chronic wasting disease in American deer and American elk in some areas of the United States and Canada, as well as Creutzfeldt-Jakob disease (CJD). These are generally not considered to be transmissible, except by direct contact with infected tissue, such as from eating infected tissue, transfusion or transplantation.

Pop Culture
This disease shows up in Chuck Klosterman's first novel, Downtown Owl. Alma, the wife of Horace, contracts this disease and the stages of insanity are clearly shown. At the end of the chapter the reader is led to believe that Horace killed his wife. This is Horace's greatest secret.