Disease Motifs
Investigating the Biomechanics of Disease
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Fatal Familial Insomnia FFI

The first collection of the symptoms under the term of fatal familial insomnia FFI was made in the eighties, and was made in the diagnosis of the disease that afflicted a large Italian family. The main characteristic in FFI involves the disturbance of the sleep-wake cycle with an individual having chronic nocturnal insomnia. The patterns that are seen on the electroencephalogram, which can record the brain activity of a sleeping person, shows that this brain activity is totally disrupted and changed. The insomnia may initial be relatively minor but gradually there is a progressive degradation of the ability of an individual to sleep, and eventually sleep may no longer be possible. There is then a waking stupor in which vivid dreams may be acted out and a near complete reduction in REM brain patterns which is replaced by other wave patterns.

There are hormonal disturbances that can be observed too, such as a reduction in the levels of melatonin and thyrotropin TSH. The brain does not seem to have great abnormalities and there is no spongiform observed though there is loss of neurones in the anterior ventral and dorsomedial nuclear group.

There is a polymorphism where aspartic acid is changed to asparagine D178N which is interestingly becasue this has also been described in CJD patients. However it is believed that there is some cis (sideways or adjacent) connection with the amino acid at position 129 which influences whether an individual becomes affected with CJD or FFI. If an individual has a methionine at position 129 (129M) as well as the polymorphism D178N then they develop FFI; but if they had a valine at position 129 (129V) along with D178N then they develop CJD.

The Human Prion Protein with the FFI Mutation D178N

The diagram below shows the mutation that leads to people being susceptible to FFI. This is the genetic form of the disease 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. See the rings draw on the illustration. I have actually removed the aspartic acid (D) residue and replaced it with the asparagine (N).

The FFI mutation D178N with 129M

There is also a sporadic form of FFI in which there are individuals who have developed the disease but who have not got this D178N mutation.