Prevalence Of Familial Mediterranean Fever Research Articles

Familial Mediterranean fever in patients with inflammatory bowel diseases: A nationwide study from the epi-IIRN.

Inflammatory Bowel Diseases (IBD) and Familial Mediterranean Fever (FMF) are auto-inflammatory diseases with common clinical and biological features. We aimed to determine their association and characterize the natural history in patients with both diagnoses. Utilizing data from the epi-IIRN cohort, which includes 98% of Israel's population, we calculated the adjusted prevalence of FMF among IBD patients vs non-IBD controls. Case ascertainment of IBD was determined according to validated algorithms and for FMF by ICD-9 codes and colchicine purchase. In total, 34 375 IBD patients (56% Crohn's disease [CD] and 44% ulcerative colitis [UC]) were compared with 93 602 matched controls. Among IBD patients, 157 (0.5%) had FMF compared with 160 (0.2%) of non-IBD controls (OR = 2.68 [95%CI 2.2-3.3]; p< 0.001). Pediatric-onset IBD had a higher prevalence of FMF compared with adult-onset IBD (30/5,243 [0.6%] vs 127/29 132 [0.4%]), without statistical significanse (OR = 1.31 [0.88-1.96]; p= 0.2). FMF was more prevalent in CD (114/19 264 [0.6%]) than UC (43/15 111 [0.3%]; OR = 2.1 [1.5-3.0]), p< 0.001). FMF diagnosis preceded that of IBD in 130/157 cases (83%). FMF was associated with a more severe disease activity in UC patients at diagnosis, but not in CD patients. Outcomes were comparable between patients with CD+FMF vs CD alone; however in patients with UC+FMF, time to biologic treatment was shorter. FMF is more prevalent in IBD patients than in the general population, particularly in CD. The diagnosis of FMF precedes the diagnosis of IBD in most cases, and may be associated with a more severe course in UC.

Abstract 26 — Clinical Characteristics of Familial Mediterranean: Fever in Hemodialysis Patients

Introduction Familial Mediterranean fever (FMF) is an inherited genetic disorder characterized by recurrent episodes of fever, serositis, arthritis, and skin rash. Uncontrolled disease can lead to amyloid A disposition, nephrotic syndrome and progressive renal failure. Recurrence of AA amyloidosis post kidney transplantation has been reported. Long-term colchicine therapy will reduce the FMF attacks and risk of AA amyloidosis. Although there is high prevalence of FMF in MENA region, the data of end stage renal disease (ESRD) in FMF is limited. We report our center experience. Method A retrospective chart review study was conducted at Tawam Hospital over 12 years (January 2010 to January 2023). We included adult ESRD on hemodialysis with FMF disease and studied their management outcomes. Descriptive analysis was used. Results 1900 ESRD patients were on hemodialysis during study period, and only two patients were diagnosed with FMF and renal amyloidosis. Case 1: A 60-year-old male patient from Syria who is known to have FMF and polycystic kidney disease leading to ESRD. He underwent successful LRD kidney transplantation in 2009. He was on mycophenolic acid: 540 mg, BID, prednisolone: 5 mg, tacrolimus: 1 mg am, 0.5 mg and colchicine 0.5 mg BID. He developed progressive renal allograft dysfunction with evidence of nephrotic syndrome. The renal biopsy revealed recurrence of AA amyloidosis due to FMF in kidney allograft in 2018. He had decline in renal function over years was initiated on hemodialysis on 2022. He developed two attacks of FMF peritonitis while on hemodialysis that responded well to steroid/colchicine therapy. Case 2: 48 years old male, from Egypt, known to have irritable bowel syndrome. He presented to our hospital with bilateral lower limb edema, and progressive shortness of breath for one month. Investigations revealed heavy proteinuria (8.98 g/g Creat) and acute kidney injury. Serology and autoimmune workup were negative. Kidney biopsy showed renal amyloidosis, and chronic tubulointerstitial nephritis with severe interstitial fibrosis (60%). History taken again and was positive for FMF in his uncle. Genetic study and clinical confirmed the diagnosis of FMF. He was started on colchicine, but developed ESRD within 8 months and initiated on hemodialysis. He had attacks of FMF. Conclusion Renal amyloidosis in FMF patient leads to progressive renal failure despite colchicine therapy. In our dialysis cohort over 12 years, only two FMF patients were identified. Colchicine therapy is required in ESRD-FMF in order to managed FMF attacks and prevent other organ AA amyloidosis.

11.4 The Association Between Childhood ADHD and the Prevalence of Familial Mediterranean Fever in Children: A Population-Based Case-Control Study

11.4 The Association Between Childhood ADHD and the Prevalence of Familial Mediterranean Fever in Children: A Population-Based Case-Control Study

Budget impact analysis of anakinra in the treatment of familial Mediterranean fever in Italy

ABSTRACT Introduction: Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disease that significantly reduces occupational productivity and quality-of-life in affected patients. Italy has an estimated FMF prevalence of 1 in 60,000 people. While colchicine is the primary treatment for FMF, biologics are administered to intolerant and non-responder patients. Anakinra and canakinumab are the only biologics approved and reimbursed for FMF in Italy. Both medicines have demonstrated efficacy in FMF patients yet differ in treatment costs. This study aimed to perform a budget impact analysis (BIA) following anakinra’s reimbursement for FMF treatment, considering pharmaceutical costs from the Italian National Healthcare Service (NHS) perspective. Methods: A ‘Reference scenario’ (all patients treated with canakinumab) was compared to an ‘Alternative scenario’, with increased anakinra market shares. The target population was estimated based on the Italian population, epidemiological and market research data. Drugs costs were estimated based on Summary of Product Characteristics and net ex-factory prices. Sensitivity analyses were implemented to test results’ robustness. Results:The base case analysis showed an overall cumulative expenditure of €30,586,628 for ‘Reference scenario’ and € 16,465,548 for ‘Alternative scenario’. A cumulative savings of €14,121,080 (46.2%) was calculated over 3 years as a result of the reimbursement and increasing uptake of anakinra. The sensitivity analyses, even considering a discount of 50% for canakinumab, confirmed the base case results. Conclusions: Anakinra’s introduction, in FMF treatment, provides a financially sustainable option for Italian patients, with savings increasing according to greater use of anakinra.

The Comparison of Pediatric Patients with Familial Mediterranean Fever Originated from Turkey and Crimea.

Objective:We aimed to evaluate the clinical and laboratory features and MEFV allele distribution in Crimean Tatar familial Mediterranean fever patients and to compare them with Turkish familial Mediterranean fever patients and healthy controls.Materials and Methods:All newly diagnosed familial Mediterranean fever patients with Crimean Tatar nationality (n = 18) in Children’s Regional Hospital in Simferopol were enrolled in the study and were compared to 40 familial Mediterranean fever cases followed up at Hacettepe University, Ankara, Turkey. The distribution of MEFV alleles was assessed in the 127 unrelated healthy Crimean Tatar adults aged 20 years or more from different parts of the Crimea peninsula.Results:Age and gender distribution, the frequency of colchicine resistance, and colchicine intolerance were similar between Turkish and Crimean Tatar children with familial Mediterranean fever. The duration of familial Mediterranean fever attack was shorter in Turkish patients than in Crimean Tatar (2.0 vs. 3.0 days, P < .001). Chest pain was more frequent in Turkish familial Mediterranean fever patients, whereas arthralgia, arthritis, and erysipeloid rash were more common in Crimean TatarT. MEFV allele distribution in Crimean Tatar was M694V-81%, M680I and V726A 9.5% both, and 68.6%, 14.3%, and 12.9% in Turkish, consequently. Homozygous carriers were 11%, compound-heterozygous was 6%, and heterozygous was 83%, compared to Turkish being 45%, 30%, and 25%, respectively. The allele distribution in healthy Crimean Tatar and Turkish was 10.2% and M694V was 7.1%, M680I was 1.6%, and V726A was 1.6%.Conclusion:The similar MEFV allele prevalence in both populations suggests the high prevalence of familial Mediterranean fever and the high number of undiagnosed patients in the Crimea peninsula. Younger age at onset, shorter duration of attacks, the prevalence of articular involvement, and erysipeloid rash were distinctive features of familial Mediterranean fever in Crimean Tatar.

MEFV mutation frequencies in a Turkish cohort with low prevalence of familial Mediterranean fever

Background/aimFamilial Mediterranean fever (FMF) is a genetically recessive autoinflammatory disease caused by mutations in the Mediterranean fever (MEFV) gene. The aim of this study was to investigate the frequencies of the most common MEFV mutations among a sample of healthy individuals from the Havsa population of European Turkey, where FMF is less prevalent compared to Asian Turkey.Materials and methodsThe study group consisted of 263 unrelated healthy adults. All of the participants were analyzed for the M694V, V726A, M680I, and E148Q mutations in the MEFV gene.ResultsIn total, 25 of the 263 individuals carried MEFV mutations (9.5%). The observed allele frequencies were 1.5% for M694V (95% confidence interval [CI] 0.5-2.5), 2.6% for E148Q (95% CI 1.6-3.9), 0.5% for M680I (95% CI 0.0-1.1), and 0.0% for V726A. The frequencies of the M694V, M680I, and E148Q mutations were not significantly different from allele frequencies (approximately 20%) determined for other regions of Turkey where FMF is more prevalent.ConclusionThese data suggest that the positivity of the MEFV gene mutation tests have lower predictive value in a population with low FMF prevalence.

Prevalence of Familial Mediterranean Fever in Children with Cryptogenic Cirrhosis.

Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by abdominal and chest pain and recurrent fever due to inflammation in the serosal membranes such as peritoneum, pleura and synovia. In FMF, recurrent inflammatory cytokine production may lead to cirrhosis. The aim of this study was to determine the prevalence of FMF in children with cryptogenic cirrhosis and it was found to be high, to add FMF among the etiological causes of cirrhosis. This prospective cohort study conducted at the Hospital of İnönü University, Malatya, Turkey. In this study, 44 patients diagnosed with cryptogenic cirrhosis by biopsy, in the Pediatric Gastroenterology, Hepatology and Nutrition Clinic, were included, after the other reasons that may cause chronic liver disease were excluded. MEVF gene analysis was performed for all patients with cryptogenic cirrhosis. FMF genetic mutation was detected in 9 (20%) of 44 patients. M694V mutation was detected in one patient (2.27%) and E148Q homozygous mutation was detected in one patient (2.27%). Various other heterozygous mutations were detected in seven other patients. Homozygous and heterozygous R202Q mutations were detected in one patient. We suggest that FMF plays a role in the etiologic differential diagnosis of cryptogenic cirrhosis.

POS1298 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).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

Contribution of Arab Countries to Familial Mediterranean Fever Research: a PubMed-based bibliometric analysis.

Familial Mediterranean Fever (FMF) is an inherited autoinflammatory disease. One of the feared complications of FMF, amyloidosis is often correlated with an increased mortality rate. The severity of the disease is linked with different mutations in the MEFV gene that may favor different outcomes (amyloidosis, Bechet's disease…). Although several countries worldwide contribute remarkably to research related to FMF, Arab countries make up only a small part of this contribution. This study aims to estimate numerically the contribution of the Arab world to research conducted on FMF. PubMed is used to quantitate the number of FMF-related articles published by each Arab country from 2004 till 2019. The retrieved numbers are normalized with respect to each country's average population and average Gross Domestic Product (GDP) and are also compared to those of some non-Arab countries having high FMF prevalence. In comparison with some non-Arab countries, the Arab world has a minor contribution of 3.80% to the total FMF-related publications, faced by 24.93% solely by Turkey. Out of total research done by Arab countries, FMF-related articles constitute no more than 0.133%. When normalized against the average population, Tunisia ranks first, followed by Lebanon. Similarly, normalizing the retrieved numbers of articles against average GDP shows that Tunisia and Lebanon come first and second, respectively. Only 8 Arab countries published a total of 13 articles concerning amyloidosis which makes 4.7% of the total Arabic FMF published articles. This study reflects an undoubtable need for more research to be conducted on FMF by the Arab countries, which suffer greatly from immense shortage in research productivity, due to the many obstacles and limitations these countries face every day.

Joint Manifestations in Children with Familial Mediterranean Fever in Armenia: Clinical and Genetic Characteristics

Familial Mediterranean fever (FMF) is an autosomal-recessive autoinflammatory disease in the group of Hereditary periodic fever syndromes (HPFS), characterized by recurrent, self-limited attacks of fever and polyserositis, which last 2-4 days. It manifests mainly in childhood and often has early onset, resolve without sequels. Genetic testing of FMF is efficient and allows diagnosing of atypical cases. FMF is a significant health care problem in Armenia because of high frequency of carriers of MEFV mutations 1:3 - 4 (0.21) and marked FMF prevalence 54.7 per 10`000 of the total population. Articular symptoms are found in about 45% of cases. They usually manifest as acute recurrent arthritis (ARA) or arthralgia, but more rarely also chronic arthritis can be found. We aimed to investigate clinical and genetic characteristics of the joint manifestations in Armenian children with FMF. The charts of all 715 patients with proven diagnosis of FMF at the National Pediatric Center (NPC) for FMF were reviewed for joint manifestations. The diagnosis of FMF and disease severity were determined according to the Tel-Hashomer criteria and molecular-genetic detection of 12 MEFV mutations common for Armenians. The characteristics of joint manifestations and overall FMF disease were then compared to MEFV mutation analysis. There were 438 boys and 277 girls with an age at diagnosis between 3 months and 17 years (mean age: 8.64±0.17). Joint involvement was observed in 56.4% of all 715 cases. The manifestation was ARA in 30.5%, arthralgia in 21.2% and chronic arthritis (CA) in 4.7%, which would also qualify for a diagnosis of JIA. The frequency of ARA was associated with M694V mutation, mainly M694V homozygous and M694V heterozygous genotypes. The risk of CA depended on MEFV genotype of the FMF patients and was the highest in M694Vheterozygotes and M694Vhomozygotes. M694V heterozygous genotype was noticed significantly more frequently among FMF patients with spondyloarthritis in comparison to those without it. The probability of the development of CA among FMF patients without M694V mutation was significantly higher also in heterozygotes in comparison to compound-heterozygotes. We concluded, that the frequency of joint involvement among Armenian pediatric FMF patients was high - 56.4%, especially for CA. Chronic arthritis may be the first manifestation of FMF and occurred usually in patients with severe M694V mutations. Patients of Armenian origin with refractory arthritis should be asked for isolated febrile attacks, hemorrhagic vasculitis, episodes of pleuritis and family history to rule out FMF.

Association of Macrophage Migration Inhibitory Factor Gene -173 G/C Polymorphism (rs755622) with Familial Mediterranean Fever in Children.

Objectives The aim of this study was to identify the genotypic analysis and allele frequencies of the -173 G/C polymorphism in the macrophage migration inhibitory factor ( MIF ) gene in children diagnosed with familial Mediterranean fever (FMF). Methods The study included 98 children who were diagnosed with FMF according to the Tel Hashomer criteria and one hundred and 57 healthy children as the control group. Genotyping was done for a polymorphism in a promoter region of the MIF gene (G/C at position -173). Results The relationship of FMF prevalence and -173 G/C genotype of the MIF gene was statistically significant. Individuals with the CC genotype seem to be predisposed to FMF. Conclusion The C/C polymorphism at position -173 of the MIF gene could be associated with excessive inflammation and immune response and can lead to susceptibility to FMF.

The Prevalence of Familial Mediterranean Fever and Behçet's Disease: A Cross-Sectional Study.

Objectives This study aims to investigate the coexistence of familial Mediterranean fever (FMF) and Behçet’s disease (BD).Patients and methods This cross-sectional study was conducted between May 2009 and August 2009. The study included 14,881 randomized children (7,741 males, 7,140 females; mean age 13.0 years; range, 12 to 14 years) from sixth to eighth grades, in 72 primary schools in the center of Turkey’s Sivas province. Of these children, 985 were randomly selected and interviewed with their parents. During these interviews, the family trees up to second-degree relatives were drawn. The presence of a diagnosis of FMF or BD was questioned. Patient history, physical examination, eye examination, and pathergy test were performed when needed. The methods of this study were reported in accordance with the STrengthening the Reporting of OBservational studies in Epidemiology guidelines.Results Nine hundred and eighty-five students, 978 mothers, 953 fathers, and 1,876 relatives (4,792 in total) were included in the study. The ratio of consanguineous marriage ratio was 13.6%. Only 30 patients (0.6%) were diagnosed with FMF, while three (0.06%) were diagnosed with BD. In patients with FMF, consanguineous marriage was statistically significant (p=0.015). In terms of low back, heel, and joint pain and morning stiffness, there was a statistically significant difference between patients with and without FMF (p<0.05). Of the three BD patients, one had concomitant FMF.Conclusion The prevalence of FMF in Sivas province was higher than Turkey’s prevalence; however, the prevalence of BD was lower. According to these findings, it is not easy to conclude that the two diseases share a common pathogenesis.

P733 The influence of concomitant familial Mediterranean fewer on Crohn’s disease course: Data from an FMF endemic area

Abstract Background Crohn’s disease (CD) and Familial Mediterranean fever (FMF) are both inflammatory disorders characterised by recurrent abdominal pain and fever attacks. Mutations of Mediterranean (MEFV) gene appear to be associated with stricturing behaviour and extraintestinal manifestations of CD. Further clinical studies regarding progression of CD in coexistence with FMF is still required. The aim of this study was to evaluate the influence of concomitant FMF in CD patients on the course of the CD in FMF endemic area. Methods Total 210 adult patients who had diagnosed with CD with or without FMF between November 2006 and April 2019 were respectively examined. FMF diagnoses were based on Tel-Hashomer criteria. The Montreal classification was used to define location and behaviour of CD. CD patients were divided into two groups FMF positive and FMF negative. Severity of CD was assessed by the need for hospitalisation related to CD, whether biological therapy was received and/or whether surgery was undergone due to CD. All demographic features, MEFV mutations, location/behaviour of disease, and extraintestinal manifestations were analysed retrospectively. Results In the present study, 8 (3.8%) of the total 210 CD patients have concomitant FMF. Mean follow-up time in CD-FMF was 59.55 months and CD-non-FMF was 60.98 months. CD patients with or without FMF showed similar demographic features including age, sex, smoking behaviour, disease location, behaviour, and treatment regimen in maintenance of the remission. Regarding extraintestinal manifestations, only peripheral arthritis was found significantly higher in CD-FMF patients (n = 3, 37.5%) compared CD-non-FMF patients (n = 21, 10.4%). In the CD-FMF patients, a result of MEFV mutation gene analysis was found in medical records 6 patients. Of those, 2 had homozygote MEFV mutation, 2 had heterozygote MEFV mutation and 2 without any MEFV mutations. In CD-FMF group, percentage of patients on biological therapy (n = 4, 50%) was significantly higher than CD-non FMF group (n = 24, 11.9%) (p = 0.012). Steroid dependence and hospitalisation in CD-FMF (n = 3, 37.5% and n = 5, 62.5%) group were relatively higher than CD-non-FMF (n = 83, 41.1%) group, but not statistically significant. The percentage of CD-FMF patients who underwent intestinal surgery (n = 1, 12.5%) was similar to that of CD-non-FMF (n = 33, 16.3%). Conclusion In the current study, the prevalence of FMF in CD patients was detected 3.8% in FMF endemic area. The group of patients on biological therapy in CD-FMF patients was significantly higher than CD-non-FMF patients. Frequency of hospitalisation in CD-FMF patients was relatively higher than CD-non-FMF patients. Our findings indicate that concomitant FMF in CD patients may have a negative effect on the course of CD.

Molecular Patterns of MEFV Gene Mutations in Egyptian Patients with Familial Mediterranean Fever: A Retrospective Cohort Study.

Background Familial Mediterranean Fever (FMF) is a hereditary autosomal recessive disease which is mainly seen in the Turks, Armenians, Arabs, and Jews. It is characterized by recurrent episodes of fever, polyserositis, and rash. MEFV gene, encoding pyrin protein, is located on the short arm of chromosome 16. FMF is associated with a broad mutational spectrum in this gene. Certain mutations are more common in particular ethnic groups. To date, different mutations of MEFV were observed in studies carried out in different regions worldwide. However, most of these studies did not extensively investigate the Egyptian population, in spite of the high prevalence of FMF in this geographical region. Aim To identify the frequency of MEFV gene mutations among the patients who presented with FMF like symptoms and, to characterize the different genetic mutations and their association with increased Amyloid A among Egyptian patients. Methods FMF Strip Assay (Vienna Lab Diagnostics, Vienna, Austria) was used. This test is based on reverse hybridization of biotinylated PCR products on immobilized oligonucleotides for mutations and controls in a parallel array of allele-specific oligonucleotides. Results Among the 1387 patients presenting with signs and symptoms suggestive of FMF, 793 (57.2%) were of undefined mutations, whereas 594 had MEFV gene mutations. 363 patients (26.2%) were heterozygous mutants, 175 patients (12.6%) were compound heterozygous mutants, and 56 patients (4%) were homozygous mutants. The most commonly encountered gene mutations in heterozygous and homozygous groups were E148Q (38.6%), M694I (18.1%), and V726A (15.8%). The most commonly encountered gene mutations in the compound heterozygous groups were E148Q+M694I observed in 20.6% of the patients, followed by M694I+V726A and M6801+V726A found in 18.9% and 11.4 %, respectively. The most commonly encountered gene mutation associated with abdominal pain, fever, and high serum Amyloid A was E148Q allele (37.5%). Conclusions Unlike all previous publications, E148Q allele was found to be the most frequent in the studied patients. Moreover, this allele was associated with increased Amyloid A. 793 patients were free of the 12 studied Mediterranean mutations, which implies the necessity to perform future sequencing studies to reveal other mutations.

Familial Mediterranean Gene (MEFV) Mutation in Parents of Children with Familial Mediterranean Fever: What Are the Exceptions?

Objectives Familial Mediterranean Fever (FMF) is one of the most prevalent periodic fever syndromes; MEFV, the responsible gene for the disease, is in the short arm of chromosome16. In the considerable count of the FMF patients, only one mutation is found in the MEFV and parents, who were the obligatory carriers for that mutation, were asymptomatic. The aim of this study was to evaluate these asymptomatic parents in regard to mutation in MEFV gene and similarity between parents and offspring patients. Methods In this cross-sectional study, asymptomatic parents of FMF patients enrolled the study were referred to periodic fever clinic or pediatric rheumatology clinic of Tehran University of Medical Sciences. The patients should have at least one mutation in MEFV gene and none of them had any family history of autoinflammatory disease. Twelve mutations in MEFV gene were assessed in the parents by Vienna Lab FMF Strip Assay kit by MAS PCR/Reverse hybridization. Results Forty-three patients and their parents participated in the study. Sixty-three percent (27) of patients were male. Onset of disease symptoms in 31 patients (72%) was before 4 years of old. Nine (21%) of the patients had homozygote, 16 (37%) compound heterozygote, and 17(40%) heterozygote for MEFV mutation; there was a case of complex alleles mutations (2%). M694V/M694V in 4 patients (9%) was the most homozygote genotype, and M694V/R761H in 4 (9%) and E148Q in 7 (16%) were the most compound heterozygote and heterozygote genotype, respectively. M694V, M680I, and E148Q were the most mutation in the parents. Overall, 41 patients had mutations similar to their parents' mutation, except 2 whose parents had no mutation, but a patient did. Conclusion It seems that occurrence of new mutations in offspring is not prevalent among FMF patients and there are other reasons for different clinical presentation in similar mutation carriers. On the other hand, in ethnicities with high prevalence of FMF, new mutation in descendant may occur, infrequently.

Familial Mediterranean fever is no longer a rare disease in Japan.

BackgroundThe aim of this study was to evaluate the clinical manifestations and prevalence of familial Mediterranean fever (FMF) in Japanese patients with unexplained fever and rheumatic manifestations.MethodsWe enrolled 601 patients with unexplained fever or suspected FMF throughout Japan between 2009 and 2015. Patients were divided into three groups according to Tel Hashomer criteria: sure FMF, probable FMF, and non-FMF patients, including definitive rheumatic diseases. Mutation detection in exons 1, 2, 3, and 10 of the FMF gene MEFV was performed by direct sequencing.ResultsA total of 192 patients (31.9 %) were diagnosed with FMF according to FMF diagnostic criteria. These could be divided into sure FMF (56.3 %, n = 108) and probable FMF (43.7 %, n = 84) patients. Fever, abdominal symptoms, and thoracic symptoms were significantly more common in FMF than non-FMF patients. Among FMF patients, 26 (13.5 %) had concomitant rheumatic diseases. Most FMF patients (94.3 %, 181/192) carried at least one MEFV mutation. Allele frequencies of M694I (13.5 % vs 0 %) and E148Q (39.1 % vs 24.8 %) mutations were significantly higher in FMF compared with healthy subjects. Allele frequencies of common MEFV mutations in FMF patients were M694I (13.5 %), P369S (8.6 %), R408Q (8.1 %), G304R (2.9 %), R202Q (4.4 %), E148Q (39.1 %), L110P (11.7 %), and E84K (3.1 %). Patients with a sure FMF phenotype had a higher frequency of MEFV exon 10 mutation (M694I) and a lower frequency of MEFV exon 3 mutations (P369S, R408Q) compared with those with a probable FMF phenotype.ConclusionThe high prevalence of FMF in Japanese patients with unexplained fever was confirmed in the present study. FMF should be suspected in cases of unexplained fever or non-specific rheumatic manifestations, and mutational analysis of MEFV could be useful to predict the clinical phenotypes of FMF in Japan.

How long is the diagnosis of Familial Mediterranean Fever (FMF) delayed in a region where FMF is common in Turkey?

Background and question Similar to other autoinflammatory diseases, diagnosis of FMF is often missed and markedly delayed, particularly when its prevalance is very low in a community. It’s reported that diagnosis of FMF might be delayed more than 20 years. Although Turkey is one of the countries with a high prevalence of FMF, the diagnosis of the disease is markedly delayed in clinical practice. In this study, we aimed to investigate the delay of diagnosis in patients followed up due to, or new diagnosed with FMF in the newly established Rheumatology Unit of a big tertiary medical center located in Corum region. Corum province is one of the region where FMF is very common in Turkey.

THU0383 Is There A Difference between the Western and Eastern Turkish Familial Mediteranean Fever Patients?

BackgroundThe prevalence of familial mediterranean fever (FMF) is relatively lower in western regions of Turkey compared with Eastern Anatolia. Likewise, the disease is quite uncommon in Greece and other Balkan...

P wave dispersion and QT dispersion in adult Turkish migrants with familial mediterranean fever living in Germany.

Background: Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disease associated with subclinical inflammation, which includes atherosclerosis arising from endothelial inflammation, which in turn increases the risk of atrial or ventricular arrhythmias. Conduction abnormalities can be detected using the electrocardiographic (ECG) indices P and QT dispersion (Pdisp and QTdisp). Currently, it is unknown whether patients with FMF are more likely to have abnormalities of these ECG indices. Moreover, existing studies were conducted in countries with higher FMF prevalence. We therefore perform the first prospective study assessing Pdisp and QTdisp in adult FMF patients in Germany, where prevalence of FMF is low.Method: Asymptomatic FMF patients (n=30) of Turkish ancestry living in Germany and age-matched healthy controls (n=37) were prospectively assessed using 12-lead ECG.Results: Patients and controls were comparable in gender and body mass index, and patients had higher erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and serum amyloid A (SAA) compared to controls (ESR: 23.7±14.3 vs. 16.1±13,3 mm/1sth, p=0.03, CRP: 0.73±0.9 vs. 0.26±0.4 g/dl, p=0.01, SAA: 3.14±4,8 vs. 0.37±0.3 mg/dl, p<0.01). No statistically significant difference between patients and controls respectively, for Pdisp (43.7±11.9 vs. 47.1±11.2ms, p=0.23), QTdisp (65.9±12.3 vs. 67.6±12.7 ms, p=0.58) or corrected QTdisp (cQTdisp: 73.9±15.0 vs. 76.0±13.3 ms, p=0.55) was found. No correlation could be found between Pdisp or QTdisp or cQTdisp and any of the biochemical markers of inflammation.Conclusion: FMF patients living in Germany show a Pdisp and QTdisp comparable to healthy controls, with no increased risk of atrial or ventricular arrhythmias indicated.

PReS-FINAL-2209: MEFV gene mutations in central and south-eastern European countries

Familial Mediterranean fever (FMF) is rarely reported in patients from central and south-eastern European countries (CSEE). The reason for this might be that the prevalence of FMF in CSEE is exceedingly low or that the disease is significantly under-recognized among local physicians. Moreover, genetic testing is not available in most of the countries in the region.