Fatal familial insomnia

Fatal familial insomnia (FFI) is a very rare autosomal dominant inherited prion disease of the brain. It is almost always caused by a mutation to the protein PrPC, but it can also develop spontaneously in patients without the inherited mutation in a variant called sporadic fatal insomnia (SFI). The mutated protein, called PrPSc, has been found in just 40 families worldwide, affecting about 100 people; 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. The first recorded victim was an Italian man, deceased in Venice in the year 1765.

The prion
Gene PRNP that provides instructions for making the prion protein PrPC is located on the short (p) arm of chromosome 20 at position p13. Both FFI patients and those with Creutzfeldt-Jakob disease carry a mutation at codon 178 of the prion protein gene. FFI is invariably linked to the presence of the methionine codon at position 129 of the mutant allele, whereas CJD is linked to the presence of the valine codon at that position. . "The disease is where there is a change of amino acid at position 178 when a asparagine (N) is found instead of the normal aspartic acid (D). This has to be accompanied with a methionine at position 129."

Presentation
The age of onset is variable, ranging from 35 to 60, with an average of 50. However the disease tends to prominently occur in later years, primarily following childbirth. The disease can be detected prior to onset by genetic testing. Death usually occurs between 7 and 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, after which death follows.

Other symptoms include profuse sweating, pinprick pupils, the sudden entrance into menopause for women and impotence for men, neck stiffness, and elevation of blood pressure and heart rate. Constipation is common as well.

Treatment
There is no cure or treatment for FFI. Gene therapy is so far unsuccessful. 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.

Several cases have proven that sleeping pills and barbiturates do not help; they make FFI worse and actually speed up the disease.

One of the most notable cases is that of Michael Corke, a music teacher from Chicago, Illinois. He suddenly began to have trouble sleeping not long after his 40th birthday in 1991, and his health and state of mind quickly deteriorated as his sleeplessness grew worse. Eventually, he couldn't sleep at all, and he was soon admitted to hospital. Doctors there weren't sure what was wrong with him, initially diagnosing Multiple Sclerosis; in a bid to send him to sleep in the later stages of the disease, physicians induced a coma with the use of sedatives, but they found that his brain still failed to shut down. Corke died in 1992 a month before his 41st birthday, by which time he had gone without sleep for six months.

In the late 2000s, a mouse model was made for FFI. These mice express a humanized version of the PrP protein that also contains the D178N FFI mutation. These mice appear to have progressively fewer and shorter periods of uninterrupted sleep, damage in the thalamus, and early deaths, similar to people with FFI.

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). Until recently prion diseases were only thought to be transmissible via direct contact with infected tissue, such as from eating infected tissue, transfusion or transplantation; new research now suggests that prion diseases can be transmitted via aerosols, but that the general public is not at risk of airborne infection.