Fatal familial insomnia

Overview
Fatal familial insomnia (FFI) is a very rare autosomal dominant inherited disease of the brain. The dominant gene responsible has been found in just 40 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
It 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. When another member of the family fell ill in 1984, his 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): aspartic acid-178 is replaced by asparagine 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. 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 and phobias. This stage lasts about four months.
 * 2) Hallucinations and panic attacks become noticeable, continuing about five months.
 * 3) Complete inability to sleep is followed by rapid loss of weight. This lasts about three months.
 * 4) Dementia, turning 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; hopes rest on the so far unsuccessful gene therapy. Sleeping pills have no effect.

While it is not currently possible to reverse the underlying illness, there is some evidence that treatment modalities 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 Rocky Mountains). Some forms of congestive heart failure are also believed to be caused by variant prion, 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 cannibalism, transfusion or transplantation.