Prevalence Of Familial Mediterranean Fever Research Articles

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.

PW01-033 – Phenotype – genotype in Armenian children with FMF

Familial Mediterranean Fever (FMF) is an ethnic disease for Armenian population and represents a significant health care problem. Frequency of carriers of MEFV mutations is 1:3, and the prevalence of FMF is rather high (14-100:10000). During the period between 2003 and 2012 there was a 4.5-fold increase of the total number of children with FMF. Many of these cases have severe clinical picture and atypical course, which may complicate timely diagnosis.

The Risk of Familial Mediterranean Fever in MEFV Heterozygotes: A Statistical Approach

BackgroundFamilial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disorder due to MEFV mutations and one of the most frequent Mediterranean genetic diseases. The observation of many heterozygous patients in whom a second mutated allele was excluded led to the proposal that heterozygosity could be causal. However, heterozygosity might be coincidental in many patients due to the very high rate of mutations in Mediterranean populations.ObjectiveTo better delineate the pathogenicity of heterozygosity in order to improve genetic counselling and disease management.MethodsComplementary statistical approaches were used: estimation of FMF prevalence at population levels, genotype comparison in siblings from 63 familial forms, and genotype study in 557 patients from four Mediterranean populations.ResultsAt the population level, we did not observe any contribution of heterozygosity to disease prevalence. In affected siblings of patients carrying two MEFV mutations, 92% carry two mutated alleles, whereas 4% are heterozygous with typical FMF diagnosis. We demonstrated statistically that patients are more likely to be heterozygous than healthy individuals, as shown by the higher ratio heterozygous carriers/non carriers in patients (p<10−7–p<0.003). The risk for heterozygotes to develop FMF was estimated between 2.1×10−3 and 5.8×10−3 and the relative risk, as compared to non carriers, between 6.3 and 8.1.ConclusionsThis is the first statistical demonstration that heterozygosity is not responsible for classical Mendelian FMF per se, but constitutes a susceptibility factor for clinically-similar multifactorial forms of the disease. We also provide a first estimate of the risk for heterozygotes to develop FMF.

Is familial Mediterranean fever (FMF) common in patients with negative appendectomy?

Objectives Familial Mediterranean fever (FMF) is an autosomal-recessive disease characterized by recurrent attacks of fever with serositis. Differential diagnosis of a FMF abdominal attack with acute abdomen is difficult. Acute appendicitis is the most common cause of acute abdominal pain that requires surgical treatment. The aim of this study was to investigate frequency of FMF in patients with negative appendectomy.Methods We assessed 278 patients (female/male 127/151) who were operated with preoperative diagnosis of acute appendicitis. In 250 of the patients, definitive diagnosis of acute appendicitis was established by histo-pathological examination. Patients with negative appendectomy were assessed for FMF by rheumatologist.Results Negative appendectomy was detected in 28 patients (M/F 5/23, mean age 25.3 ± 8.4 years). Negative appendectomy ratio was 10.1 %. Among 28 patients two had FMF (7.7 %).Conclusions FMF were established in 7.7 % of patients with negative appendectomy. Our study suggests patients having negative appendectomy should be evaluated for FMF. Further large sample studies are needed to define the real prevalence of FMF among negative appendectomy patients.

Familial Mediterranean fever in Germany: clinical presentation and amyloidosis risk

Objective: To characterize patients with familial Mediterranean fever (FMF) with and without AA amyloidosis living in Germany.Method: Clinical and genetic data from 64 FMF patients were analysed for amyloidosis risk factors.Results: Fifty-five patients (85%) were of Turkish or Armenian origin. Thirty-one patients (48%) developed FMF symptoms before the age of 16 years. Sixteen patients (26%) became symptomatic after age 20. Symptoms reported were peritonitis (95%), fever (78%), pleuritis (59%), arthralgia (60%), arthritis (32%), erysipelas-like erythema (23%), and vasculitis (8%). FMF diagnosis was delayed for a median of 8.0 years. Genetic analysis confirmed M694V as the most prevalent Mediterranean fever (MEFV) gene mutation in 46 out of 59 patients (78%). M694V homozygosity was associated with an earlier FMF onset (median age 5.5 years, p = 0.0001) and a higher prevalence of peritonitis (p = 0.007) and pleuritis (p = 0.0007) compared to patients without an M694V mutation. AA amyloidosis was detected in 16 patients (25%) at a median age of 36.5 years and tended to be associated with a higher age at disease onset (p = 0.062) and a higher FMF activity score (p = 0.093). AA amyloidosis was significantly associated with a higher age at FMF diagnosis (p = 0.0022).Conclusions: Clinical symptoms of FMF-affected migrants living in Germany resemble those observed in their home country. In particular, patients with an onset of FMF symptoms after age 20 and a later FMF diagnosis have a high risk of AA amyloidosis. Symptomatic patients who originate from countries with a higher FMF prevalence should be screened for FMF and proteinuria.

Familial Mediterranean Fever in Japan

Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disease that is prevalent in Mediterranean populations. While it is considered a rare disease in the rest of world, a significant number of FMF patients have been reported in East Asia, including Japan. Our aim was to determine the prevalence of FMF in Japan and elucidate the clinical and genetic features of Japanese patients. A primary nationwide survey of FMF was conducted between January and December 2009. Hospitals specializing in pediatrics and hospitals with pediatric, internal medicine, and rheumatology/allergy departments were asked to report all patients with FMF during the survey year. The estimated total number of Japanese FMF patients was 292 (95% confidence interval, 187-398 people). We evaluated the clinical and genetic profiles of Japanese patients from the data obtained in a secondary survey of 134 FMF patients. High-grade fever was observed in 95.5%, chest pain (pleuritis symptoms) in 36.9%, abdominal pain (peritonitis symptoms) in 62.7%, and arthritis in 31.3%. Of the patients profiled, 25.4% of patients experienced their first attack before 10 years of age, 37.3% in their teens, and 37.3% after age 20 years. Colchicine was effective in 91.8% of patients at a relatively low dose (mean dose, 0.89 ± 0.45 mg/d). AA amyloidosis was confirmed in 5 patients (3.7%). Of the 126 patients studied, 109 (86.5%) were positive for 1 or more genetic mutations and 17 (13.5%) had no mutation detected. Common Mediterranean fever gene (MEFV) mutations were E148Q/M694I (19.8%) and M694I/normal (12.7%). The differences in the prevalence of peritonitis, pleuritis, and a family history of FMF were statistically significant between FMF patients with MEFV exon 10 mutations compared with those without exon 10 mutations.In conclusion, a significant number of patients with FMF exist in Japan. Although Japanese patients with FMF are clinically or genetically different from Mediterranean patients, the delay in diagnosis is an issue that should be resolved.

Is familial Mediterranean fever (FMF) common in patients with negative appendectomy?

Familial Mediterranean fever (FMF) is an autosomal-recessive disease characterized by recurrent attacks of fever with serositis. Differential diagnosis of a FMF abdominal attack with acute abdomen is difficult. Acute appendicitis is the most common cause of acute abdominal pain that requires surgical treatment. The aim of this study was to investigate frequency of FMF in patients with negative appendectomy. We assessed 278 patients (female/male 127/151) who were operated with preoperative diagnosis of acute appendicitis. In 250 of the patients, definitive diagnosis of acute appendicitis was established by histo-pathological examination. Patients with negative appendectomy were assessed for FMF by rheumatologist. Negative appendectomy was detected in 28 patients (M/F 5/23, mean age 25.3 ± 8.4 years). Negative appendectomy ratio was 10.1 %. Among 28 patients two had FMF (7.7 %). FMF were established in 7.7 % of patients with negative appendectomy. Our study suggests patients having negative appendectomy should be evaluated for FMF. Further large sample studies are needed to define the real prevalence of FMF among negative appendectomy patients.

Association of familial Mediterranean fever–related MEFV variations with ankylosing spondylitis

The pathogenesis of ankylosing spondylitis (AS) has a strong genetic contribution. Familial Mediterranean fever (FMF) is an autosomal recessively inherited autoinflammatory disorder caused by MEFV gene missense variations, and a clinical association between FMF and AS has been reported previously. The aim of this study was to analyze the association of common MEFV variations (M694V, M680I, V726A, and E148Q) with AS in a group of Turkish patients. The study group comprised 193 patients with AS and 103 matched healthy control subjects. All individuals were genotyped for 4 MEFV variations and HLA-B27 using genomic DNA, and association of the variations with the clinical and laboratory features of the patients was analyzed. The MEFV missense variations were significantly more frequent in patients with AS (22.3%) compared with healthy control subjects (9.7%; odds ratio [OR] 2.67, 95% confidence interval [95% CI] 1.28-5.56). This difference was more prominent for exon 10 variations (M694V, V726A, M680I) (OR 3.75, 95% CI 1.41-9.97), especially for the most-penetrant variation M694V (OR 4.73, 95% CI 1.39-16.12). MEFV variations were more frequent in HLA-B27-negative patients with AS, and the difference was statistically significant in patients carrying exon 10 variants. FMF-related MEFV variations are associated with AS, and these variations may contribute to the pathogenesis of AS, especially in populations in which the prevalence of FMF is high.

Acute adrenal crisis mimicking familial Mediterranean fever attack in a renal transplant FMF patient with amyloid goiter

The most devastating complication of familial Mediterranean fever (FMF) is amyloidosis which is capable of resulting in chronic renal failure. Although amyloid deposits are frequent in adrenal glands based on the autopsies of FMF patients however; to our knowledge, symptomatic adrenal insufficiency has not been reported yet. We describe a 21-year-old-FMF amyloidosis case with a well-functioning allograft who presented to the emergency clinic with the complaints of abdominal pain, vomiting and diarrhea mimicking FMF attack. adrenocorticotrophic hormone stimulation test was performed due to resistant hyponatremia and disclosed Addison disease. In countries with a high prevalence of FMF, adrenal crisis should be borne in mind in long standing FMF patients.

Investigation of C5a receptor gene 450 C/T polymorphism in Turkish patients with familial Mediterranean fever

Familial Mediterranean fever (FMF) is a genetic disorder with acute inflammatory serosal attacks due to MEFV gene mutations which resides in chromosome 16. Lack of a C5a inhibitor activity in the peritoneum has previously been proposed in part to contribute in propagation of the serosal inflammation in FMF attacks. The aim of this study is to investigate C5a receptor (C5aR) gene polymorphism in patients with FMF and its relation to the main features of the disease. A polymorphism in the coding region of C5aR gene leading to C to T transition at nucleotide position 450 has been investigated in 85 non-related Turkish FMF patients and 160 non-related healthy controls by using PCR-RFLP. The frequencies of C5aR gene 450 CT genotype and T allele were not significantly different between Turkish FMF patients and healthy subjects (14.12 and 8.24% for FMF vs. 10 and 5% for controls, respectively). C5aR gene 450 CT genotype tended to associate with the presence Henoch-Schonlein purpura (OR: 1.25, 95% CI: 0.917-1.704, P = 0.017) but with no other clinical findings of the disease. C5aR polymorphism might be searched in populations having high prevalence of FMF.

MEFV mutation carriage in Israeli Jewish individuals from ethnicities with low risk for familial Mediterranean fever

Familial Mediterranean fever (FMF) is a disease caused by mutations in the MEditerranean FeVer gene (MEFV), and in Israel it most commonly affects Jews of North African extraction, in whom the mutation carrier rate is as high as 1 in 5. To assess the protective as well as the modulating affect of MEFV mutation carriage on various inflammatory disease states, we sought to define the frequency of MEFV mutations in Israeli Jewish individuals of various ethnicities, including those with low frequency of FMF, which were not in the focus of our attention hitherto. A total of 163 adults of Bucharian, Turkish, Georgian, Yemenite and Bulgarian origin comprised the study group. The prevalence of the most frequent MEFV mutations in the Israeli Jewish population, namely: M694V, V726A and E148Q, was assessed. The association of mutation carriage with a personal history of FMF-like phenomena, as well as various inflammatory and non-inflammatory diseases, was evaluated. A high MEFV mutation frequency was found among Jews of Bucharian, Georgian and Bulgarian origin (20%), whereas intermediate and low rates were detected in Jews of Turkish and Yemenite extraction (14 and 8%, respectively). FMF-like manifestations and related diseases were observed more often in MEFV mutation carriers than in their counterparts. MEFV mutation frequency, directly assessed by DNA analysis, exceeds the rate calculated from disease prevalence in Israeli Jewish individuals originated from ethnicities with a low prevalence of FMF. MEFV mutation carriage in this subgroup is associated with various inflammatory disorders.

Increased frequency of familial Mediterranean fever in northern Turkey: a population-based study

Familial Mediterranean fever (FMF) is a systemic relapsing autoinflammatory disorder occurring in populations originating from the Mediterranean basin, mainly Turks, Levantine Arabs, Sephardic Jews, Druze, and Armenians. The prevalence of FMF shows considerable geographical variation. In Turkey, the prevalence rates were reported as 0.0027-0.25%. This field survey was conducted in different regions to investigate the frequency of FMF in a northern province of Turkey. This study was conducted in 70 areas (12 urban and 58 rural) in the province of Tokat, which is in northern Turkey. The population of Tokat was reported to be 828,000 at the last census in Turkey in 2000, about 530,000 for individuals aged >18 years ( http://www.die.gov.tr ). Mean age of 1,095 (541 male and 554 female; urban 555 and rural 540) subjects was 41 +/- 17 (range 18-95 years). FMF frequency in this study was 1/123 (0.82%, 95 CI: 0.40-1.61). Mean age of patients were 27 years (20-41) and mean age of symptoms were 16.3 years (11-23). In conclusion, the frequency of FMF in this study was 1/123 (0.82%) which was higher than expected. This rate is the highest frequency of FMF reported from Turkey. Further large sample studies are needed to define to true prevalence of FMF in Turkey.

Higher than expected carrier rates for familial Mediterranean fever in various Jewish ethnic groups.

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterised by recurrent attacks of inflammation of serosal membranes. Amyloidosis leading to renal failure is the most severe complication in untreated patients. In Israel FMF is most frequent among Jews of North African origin. Recently the causative gene (MEFV) has been found and the common mutations characterised. The aim of this study was to investigate the carrier rates of the common MEFV mutations among 400 healthy members of four different ethnic groups (100 in each group) in Israel, and to compare the distribution of the different mutations between FMF carriers and patients. We found a high frequency of carriers among Jews from the various ethnic groups. In North African Jews it was 22%, in Iraqi Jews 39%, in Ashkenazi Jews 21%, and in Iranian Jews 6%. The distribution of the four most common MEFV mutations among healthy individuals (M694V 29%, V726A 16%, M6801 2% and E148Q 53%) was significantly different (P < 0.003) from that found in patients (M694V 84.4%, V726A 9.0%, M6801 0% and E148Q 6.6%). Six healthy asymptomatic individuals were found to carry mutations in both alleles: two homozygotes for E148Q and four compound heterozygotes E148Q/other. These results demonstrate a very high carrier rate among all Jewish ethnic groups. They confirm that mutation E148Q is associated with a milder phenotype, which explains the lower prevalence of FMF among the Ashkenazi and Iraqi Jews. This study raises the question of the need for molecular screening for M694V homozygotes in the Israeli North African Jewish community.

Familial Mediterranean fever in Arab children: the high prevalence and gene frequency.

Over a period of 3 years, 192 children with familial Mediterranean fever were prospectively studied. Of these, 106 (55%) were girls and 86 (45%) were boys. The prevalence was 1:2600 children with a gene frequency of 1:50. The age at onset ranged between 4 months and 16 years. Of these patients 24% started their illness below the age of 2 years and 88% were symptomatic before the age of 10 years: 82% had recurrent abdominal pain, 43% had pleurisy, 37% had arthritis, 15% had cutaneous manifestations, 12% had splenomegaly and 4% had hepatomegaly. The presenting symptoms were abdominal pain in 51%, unilateral chest pain in 23% and arthritis in 26%. The family history was positive in 62%. Of 12 affected families 19 members had/have renal failure and amyloidosis was confirmed in 7 patients. Our data show a high prevalence of familial Mediterranean fever and a high gene frequency in Arab children similar to that reported in Jews and Americans.