Background Familial Mediterranean Fever (FMF) is a well-described monogenic autosomal recessive disorder with highest occurrence in the Mediterranean region. It is very rare in other areas, although with the increase of professional awareness and diagnostic availability new case-reports of FMF outside the typical regions are recently being published1. We describe our experience of one center in the Czech Republic that follows five families with members bearing mutations in MEFV gene without provable ancestry from the Mediterranean region.
Objectives The aim of the study was to evaluate the mutational status of our patients and to describe and discuss the clinical picture of the heterozygous variants which were present in the cohort.
Methods Patients were diagnosed based on clinical criteria and their respective family history and were regularly tested using certified laboratory methods – complete blood count with differential to test for neutrophilia, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum amyloid A (SAA), basic immunological tests including IgD levels, monoclonal component levels, autoantibodies and basic cellular immunity panel, including T-lymphocyte activation test. All exons and exon/intron regions of the MEFV and TNFRSF1A genes were amplified from genomic DNA by PCR and sequenced in both directions using ABI Prism 310 or ABI 3500xL Genetic analyzers.
Results In 10 patients we could confirm mutations in M694V (9 heterozygotes and 1 homozygote), 1patient had mutation in K695R and 1 patient was described as compound heterozygote for M694V and I591T. In addition, in 1patient we have identified mutations in K695R and TNFRSF1A as well. Despite the heterozygous state, the majority of the subjects had significant clinical symptomatology and required treatment with Colchicine. In two patients standard treatment regimens failed and they were further treated by IL-1 inhibition with good clinical responses.
Conclusions FMF in the Czech Republic, a country without significant consanguinity and tangible Mediterranean ethnic roots, is a very rare disease. Our group has recently identified and follows 5 families with proven mutations in MEFV gene showing, that probably this disorder may not be so rare after all. Our patients' cohort shows significant clinical symptoms of heterozygous carriers. The typical clinical presentation in heterozygotes corresponds to data described in the international literature.
Toplak N, Dolezalova P, Constantin T et al. Periodic fever syndromes in Eastern and Central European countries: results of a pediatric multinational survey. Pediatr Rheumatol Online J 2010: 8: 29.
Acknowledgements Supported by MZ ČR – RVO, FN Motol 00064203.
Disclosure of Interest None declared