Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disease with a high prevalence in some countries. The carriers of the MEFV gene causing FML are Jews, Armenians, Turks, Arabs and other nationalities of Mediterranean origin. Crimean Tatars are one of the nations that inhabit the Crimean peninsula, who do not formally belong to Mediterranean populations. Until 2016, there were no data on FMF in Crimea among the Crimean Tatar population; however, 15 new cases of FMF have been diagnosed in the Republic of Crimea in the past 2 years. The paper provides data on FML patients and information about the ethnic origin of the Crimean Tatars, explaining the possible origin of mutant alleles in the population.

Семейная средиземноморская лихорадка-типичное моногенное заболевание с аутосомно-рецессивным типом наследования; обусловлено мутациями в гене MEFV, кодирующем белок пирин. Является сравнительно редкой патологией в практике педиатров и ревматологов Российской Федерации. В статье приводятся современные данные о распространенности заболевания, представлена полная на сегодняшний день клиническая картина аутовоспалительного синдрома, рассматриваются диагностические критерии и методы лечения пациентов с семейной средиземноморской лихорадкой.

The aim of this study was to analyze the clinical, laboratory and molecular genetic data of 26 patients (15 boys, 11 girls) diagnosed with mevalonate kinase deficiency syndrome (MKD).Subjects and methods. The age of MKD manifestation ranged from 0 to 30.0 months (M – 1.5 months). Clinical manifestations and their severity were extremely diverse: from symptoms resembling Marshall’s syndrome to severe systemic manifestations with respiratory failure, hepatosplenomegaly and pancytopenia.Results/Conclusion. All patients had homozygous/compound-heterozygous mutations in the MVK gene, including 10 newly described variants. In all 20 patients, who have been treated with IL-1 inhibitors long enough to assess the effect of the treatment, drastic improvement of the condition was noted, but only in 17/20 patients achieved full remission.

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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).Table 1.Comparative data of FMF patients with Turkish and Crimean Tatar originFMF featuresTurkish (n=40)Crimean Tatars (n=18)рFamily history of FMF, n (%)16 (40)9 (50)0.477Consanguinity, n (%)8 (20)6 (33)0.272Onset age, years3.3 (2; 5)1.3 (0; 4)0.040Age at FMF diagnosis, years4.7 (3; 8)9.6 (4; 14)0.005Diagnosis delay, years0.9 (0; 2)5.5 (2; 10)0.00001Fever, n (%)33 (83)18 (100)0.058Episode duration, days2.0 (2; 3)3.0 (3; 6)0.000003Fever duration, hours48.0 (48; 72)72.0 (72; 120)0.000002Chest pain, n (%)12 (30)1 (6)0.039Chest pain duration, hours48.0 (24; 72)0.0 (0; 0)0.000001Abdominal pain, n (%)30 (75)9 (50)0.061Abdominal pain duration, hours48.0 (24; 48)24.0 (24; 24)0.043Arthritis, n (%)10 (25)16 (89)0.000006Arthralgia, n (%)19 (48)17 (94)0.0007Erysipeloid rash, n (%)0 (0)9 (50)0.000001Disclosure of Interests:None declared