Fatal Familial Insomnia (FFI) is a genetic sleep disorder - but it is a rare one. It has been diagnosed in less than 40 families worldwide, including the Chicago music teacher, Michael Corke, who featured in the BBC documentary The Man Who Never Slept.
FFI begins as an unexplained sleeplessness during middle age and rapidly develops into a fatal insomnia. It is caused by a genetic mutation which leads to a prion disease, related in nature to Mad Cow Disease (BSE or CJD) and Kuru (the laughing disease found in cannibalistic tribes in New Guinea) and even Alzheimer's Disease.
Prions are the missing link between all these diseases, and they tell us a lot about the nature of protein molecules and their ability to cause death. This article looks at the causes and symptoms of FFI, and introduces one Italian family who has unwittingly passed the disease through the generations for centuries.
Fatal insomnia is a baffling condition (and only officially discovered 10 years ago) because its symptoms resemble many common diseases - like dementia, end-stage alcoholism and encephalitis. The main symptom of FFI is the inability to sleep, and this causes high pulse and blood pressure, excessive sweating and a loss of coordination and motor skills. The disease manifests itself in four deteriorating stages:
Eventually the patient falls into a coma and dies from total insomnia. One of the most tragic aspects of FFI is that though the sufferer shows signs of dementia, they have a clear understanding of what is happening to them, while enduring the physical agony of total sleeplessness.
We now know that Fatal Familial Insomnia is a prion disease. The term prion was coined by Stanley Prusiner in the 1980s as the name for an infectious agent. Specifically, a prion is a mis-folded protein that permanently affects the structure of the brain. Prions are responsible for the outbreak of Bovine Spongiform Encephalopathy (BSE) in cattle and Creutzfeldt-Jakob Disease (CJD) in humans.
In FFI, prions eat away the thalamus region of the brain, responsible for regulating sleep and various sensory and motor systems. This increasingly prevents the sufferer from losing consciousness - although their EEG readings show signs associated with REM sleep during waking hours: they are so sleep deprived, they are dreaming while awake.
Because Fatal Familial Insomnia is genetic, there is a 50% chance of a parent passing it on to their offspring. The tragic thing is, the symptoms don't show until after the child-bearing years are over (typically over 40 years), so parents usually pass on the defective gene without realizing.
Fortunately, a diagnostic test is now available, but there is no known cure for FFI. The only hope is that gene therapy will offer a solution to future generations.
The Family That Couldn't Sleep is a fascinating book by D T Max, detailing the history of Fatal Familial Insomnia and related prion diseases. It reads like a detective story with alarming twists and turns, including just how close the population of Britain came to suffering a major epidemic of CJD.
Here's an excerpt about the book from Publisher's Weekly:
"In 1765, Venetian doctors were stumped by the death of a man who had suffered from insomnia for more than a year and spent his final months paralyzed by exhaustion. Over the next two centuries, many of his descendants would develop similarly fatal symptoms, with a range of misdiagnoses, from encephalitis to alcohol withdrawal.
Finally, in the early 1990s, their disease was recognized as a rare genetic form of prion disease. The family reluctantly shared their history of Fatal Familial Insomnia with Max, who has written about science and literature for the New York Times Magazine and other publications. Max (inspired in part by his own neuromuscular disorder) has crafted a powerfully empathetic account of their efforts to make sense of their suffering and find a cure. But this is only half the story.
Looking at prion disease in general, Max doubles back to the English Mad Cow epidemic of the 1990s, retracing established backstories among New Guinea aboriginals and European sheep herds. There's enough fascinating material - in particular, a theory suggesting that early humans were nearly wiped out by a plague spread by cannibalism - to keep readers engaged, but they're likely to want still more about the genuinely captivating family drama."
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