Unexpectedly high prevalence of familial Mediterranean fever in Slovakia.

Familial Mediterranean fever (FMF) is the most common monogenic periodic fever syndrome among all monogenic autoinflammatory diseases. It is characterised by recurrent, self-limited fever attacks of short duration, polyserositis symptoms, and elevated acute-phase reactants. FMF has the highest prevalence in the Eastern Mediterranean region. The first descriptions of FMF cases in Central Europe date back to 2014. The prevalence in the Central European region was previously estimated at 1:465,500 in the paediatric population, with data on adult prevalence lacking. Patients with FMF who fulfilled Eurofever/PRINTO diagnostic criteria were included in the study. Massive parallel sequencing of clinical exome with evaluation of virtual panel for genes associated with inborn errors of immunity and autoinflammatory conditions was used in the vast majority of the patients. Statistical analysis of clinical and laboratory manifestation was performed. The prevalence of FMF in the Slovak population of the present study was 1:48,224 (1:41,348 in children and adolescents), which is significantly higher than expected. The most common variant in our cohort was M694V, present in 52.0% of alleles. Variant K695R was observed in 29.9% which is higher than reported in the other FMF cohorts. Abdominal pain and fever were the most prevalent clinical symptoms, although up to one-third of patients also experienced atypical symptoms such as tonsillitis or cervical lymphadenopathy. This paper provides the first comprehensive analysis of the Slovak National FMF cohort, including epidemiological data, clinical manifestations, and genetic background. Our data could contribute to the general knowledge about FMF characteristics in the underreported regions.