DiscoverScroll article

Fatal insomnia is a neurodegenerative prion disease that results in trouble sleeping as its hallmark symptom.

The majority of cases are familial (fatal familial insomnia ), stemming from a mutation in the PRNP gene, with the remainder of cases occurring sporadically (sporadic fatal insomnia ). The problems with sleeping typically start out gradually and worsen over time. Eventually, the patient will succumb to total insomnia (agrypnia excitata), most often leading to other symptoms such as speech problems, coordination problems, and dementia. It results in death within a few months to a few years, and there is no known disease-modifying treatment for now.

Characterized by worsening insomnia, resulting in panic attacks, paranoia, and phobias. The presentation of the disease varies considerably from person to person, even among people within the same family; in the sporadic form, for example, sleep problems are not commonly reported, and early symptoms are ataxia, cognitive impairment, and double vision.

Fatal familial insomnia is a rare hereditary prion disease that is associated with a mutation in PRNP. Individuals with FFI or familial Creutzfeldt–Jakob disease (fCJD) both carry a mutation at codon 178 of the prion protein gene. FFI is also invariably linked to the presence of the methionine codon at position 129 of the mutant allele, whereas fCJD is linked to the presence of the valine codon at that position. FFI is an autosomal dominant disease caused by a missense GAC-to-AAC mutation at codon 178 of the PRNP prion protein gene located on chromosome 20, along with the presence of the methionine polymorphism at position 129 of the mutant allele.

A test that measures the cerebral metabolic rate of glucose is performed by positron emission tomography (PET), using the radiotracer -FDG-PET which is a glucose analogue, Fatal Familial Insomnia has demonstrated severe hypometabolism of the thalamus bilaterally in FFI and sFI, also in the earliest stages of the disease. The hypometabolism would show a build up of glucose due to the thalamus using less glucose then normal, this would also align with symptoms of insomnia like sleep regulation, autonomic and cognitive functions and motor information.

Like all prion diseases, FFI is invariably fatal.

Fatal insomnia was first described by Elio Lugaresi et al. in 1986. In 1998, 40 families were known to carry the gene for FFI globally: eight German, five Italian, four American, two French, two Australian, two British, one Japanese and one Austrian. In the Basque Country of Spain, 16 family cases of the 178N mutation were seen between 1993 and 2005 related to two families with a common ancestor in the 18th century. In 2011, another family was added to the list when researchers found the first man in the Netherlands to be diagnosed with FFI. Other prion diseases are similar to FFI and may be related but are missing the D178N gene mutation. As of 20 September 2022, 37 cases of sporadic fatal insomnia have been diagnosed. Unlike in FFI, those with sFI do not have the D178N mutation in the PRNP gene; they all have a different mutation in the same gene causing methionine homozygosity at codon 129. Nonetheless, the methionine presence in lieu of the valine (Val129) is what causes the sporadic form of disease. The targeting of this mutation has been suggested as a strategy for treatment, or possibly as a cure for the disease.

In 1986, Lugaresi and colleagues first named and described in detail the clinical and histopathological features of fatal familial insomnia. Roiter and Silvano's family, more cases were obtained, resulting in the classification of FFI as a familial prion disease tied to the 178Asn genetic mutation.

The Prion Alliance was established by husband and wife duo Eric Minikel and Sonia Vallabh after Vallabh's mother was diagnosed with the fatal disease.

Quick Facts

• The majority of cases are familial (fatal familial insomnia ), stemming from a mutation in the PRNP gene, with the remainder of cases occurring sporadically (sporadic fatal insomnia ).
• Eventually, the patient will succumb to total insomnia (agrypnia excitata), most often leading to other symptoms such as speech problems, coordination problems, and dementia.
• Fatal insomnia was first described by Elio Lugaresi et al. in 1986.
• Fatal familial insomnia is a rare hereditary prion disease that is associated with a mutation in PRNP.
• As of 20 September 2022, 37 cases of sporadic fatal insomnia have been diagnosed.

Source material: Wikipedia - "Fatal insomnia". Adapted and summarized for DiscoverScroll. Original contributors are credited through the linked Wikipedia article. Read original on Wikipedia. CC BY-SA 4.0. Changes were made from the original.