Fatal familial insomnia

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Classification according to ICD-10
A81.8 Other atypical viral infections of the central nervous system
ICD-10 online (WHO version 2019)

In the fatal familial insomnia (even lethal familial insomnia , Eng. Fatal Familial Insomnia , short FFI) is a hereditary, very rare and in the course of months to years always fatal transmissible spongiform encephalopathy (TSE).

history

The disease was first described in 1986, although it was not recognized as a TSE at the time. In 1992 the mutation leading to the disease was described in the PRNP gene and in 1995 experimental transferability was demonstrated. The strange seeming fact that a hereditary disease can be transmitted arises from the peculiarities of prion diseases .

The " BSE crisis" and the appearance of Creutzfeldt-Jakob disease in the 1990s aroused public interest in TSE diseases and thus to a certain extent in FFIs.

Clinical picture

The disease is equally common in men and women. The first symptoms appear between the ages of 37 and 62 years, with an average of 51 years.

The first symptom is difficulty falling asleep and staying asleep, resulting in drowsiness and sleepiness during the day. Later in the course of the disease, oneiroid states occur: The sick person, left to himself, falls into a dream-like state with hallucinations and behavior that corresponds to the content of the dream. In later stages of the disease, balance and gait disorders, myoclonus (muscle twitching) and signs of damage to the pyramidal tract are added. Those affected suffer from impaired attention, memory problems and other cognitive symptoms .

For diagnosis are among other polysomnography and EEG used. Patients with FFI only achieve sleep stage 1 and REM sleep for a short period of time , the deeper sleep stages 2–4 no longer occur ( Agrypnia excitata ).

There is no treatment option, and patients die within seven months to two years. Some of those affected die suddenly before a severe impairment of consciousness has set in. In others, the disease progresses to apallic syndrome . The cause of death in these patients is often pneumonia or other infection.

genetics

Fatal familial insomnia is inherited in an autosomal dominant manner, so if only one parent is affected on an allele , their children are each affected with a 50% probability. Responsible is a mutation leading to the amino acid exchange at gene location 20p13, which codes for the prion protein:

Patients with FFI have a “missense” mutation of the prion gene at codon 178 (GAC → AAC). The same mutation is found in families with Creutzfeldt-Jakob disease . Whether this mutation leads to FFI or Creutzfeldt-Jakob disease depends on a slight variation ( polymorphism ) in the prion gene: If the prion gene codes at codon 129 for the amino acid methionine, FFI occurs. If the code for valine is at this point, Creutzfeldt-Jakob disease is the result.

pathology

The most obvious changes in the histological examination of the brain are found in individual thalamic nuclei (nucleus ventralis anterior and nucleus medialis dorsalis) and in the nucleus olivaris inferior. The number of nerve cells is reduced in these areas. Slight changes are found in the cerebral cortex, other parts of the thalamus, and in the cerebellum. Spongiform, "spongy" changes in the brain tissue and deposits of prion protein are less pronounced than z. B. in the related Creutzfeldt-Jakob disease .

Epidemiology

Even among prion diseases, FFI was considered extremely rare. Slightly more cases have been diagnosed lately, presumably due to improved diagnostics . Even if you assume that there are more undiscovered cases, it will likely remain a very rare disease. Across the globe there are a double-digit number of affected families. There are also cases in Germany and Austria .

Reporting requirement

Transmissible spongiform encephalopathies are in Austria in accordance with § 1 para. 1, point 1 Epidemics Act 1950 on suspicion, illness and death notifiable . Doctors and laboratories, among others, are obliged to report this ( Section 3 Epidemics Act).

In Germany, human spongiform encephalopathy (except for familial hereditary forms) is subject to notification by name in the event of suspicion, illness and death by the doctor etc. in accordance with Section 6 of the Infection Protection Act (IfSG) . The group of reporting persons is based on § 8 IfSG, what has to be reported according to § 9 IfSG.

literature

Individual evidence

  1. ^ Niels Birbaumer & Robert Franz Schmidt: Biological Psychology . 6th edition. Springer Medizin Verlag, Heidelberg 2006, ISBN 3-540-25460-9 , p. 559 .
  2. ↑ Fatal familial insomnia.  In: Online Mendelian Inheritance in Man . (English)
  3. ↑ Fatal familial insomnia. In: Orphanet (Rare Disease Database).