Comparison Of Fmf Clinical Features Between Turkish And Crimean Tatar Children

Background: Crimean Tatars is an ethnic group in Russia. The presence of familial Mediterranean fever (FMF) has been recognized since 2016. Objectives: The study aimed to evaluate the prevalence and clinical features as well as genetic aspects of FMF in children of Crimean Tatar (CT) origin and compare them with a cohort from Turkey. Methods: This retrospective study included all FMF cases in patients of CT origin (n=18) diagnosed in Children’s Regional Hospital in Simferopol since 2016. We included 40 consecutive FMF cases between February-March 2020, diagnosed and followed at Hacettepe University, Ankara, Turkey. All children were less than 18 years old at the time of inclusion. The diagnosis of FMF was based on the EULAR criteria (2019). We excluded other autoinflammatory diseases and any doubtful cases. For assessment of MEFV alleles prevalence 127 healthy unrelated CT adults from different parts of Crimea peninsula were included. Sanger sequencing of MEFV exons 2 and 10 was performed in all the patients and controls. Results: FMF in CT was diagnosed with nearly 5 year-delay, despite the earlier age at onset. CT children had more frequent and prolonged fever, joint involvement (arthritis and arthralgia) and erysipeloid rash compared to Turkish, who had more attacks with chest pain and abdominal pain which last longer. (Table 1) CT had higher white blood cell count, C-reactive protein, erythrocyte sedimentation rate and lower hemoglobin. It might be explained by the fact that the majority of Crimean Tatars were admitted to the clinic during an attack, which was not always the case with Turkish children. Distribution of MEFV pathogenic alleles p.M694V, p.M680I, p.V726A in CT children was 81%, 9.5% and 9.5%, respectively, while in Turks it was 68.6%, 14.3% and 12.9%. Among the CT patients, proportion of homozygotes, compound-heterozygotes and heterozygotes were 11%, 6% and 83%, and among Turkish patients were 45%; 30%; and 25%, respectively. MEFV pathogenic variants were detected in 10.2% of healthy CT donors: 7.1% individuals had p.M694V, 1.6% - p.M680I, 1.6% - p.V726A. Comorbid diseases including IgA vasculitis, sacroiliitis, JIA, autoimmune hepatitis and inflammatory bowel disease were reported in 5.6% of CT and 10% of Turks. The colchicine treatment rate and regimen were similar, but CT received biologics more frequently (44%) than Turks (22.5%). Conclusion: CT is an ethnic group with a significant number of MEFV mutation carriers assuming the expected prevalence of FMF to be as high as 1:385. Thus, any periodic fever in CT patients should be considered as a sign of possible FMF. The clinical course of FMF has some peculiarities in CT patients. This work supported by the Russian Foundation for Basic Research (grant № 18-515-57001). Disclosure of Interests: None declared