Familial Mediterranean Fever Group Research Articles

THU0400 Familial Mediterranean Fever Gene (MEFV) Mutations and Disease Severity in Systemic Lupus Erythematosus (SLE); Implications on the Role of the E148Q MEFV Allele on Inflammation

BackgroundRecent observations in large and well established familial Mediterranean fever (FMF) cohorts suggested a lower than expected prevalence for SLE and SLE patients carriers for the common MEFV mutations were...

Assessment of autonomic functions in children with familial Mediterranean fever by using heart rate variability measurements.

The aim of this study is to analyze possible autonomic nerve system alterations and assess the efficacy of heart rate variability (HRV) analysis in anticipation of cardiovascular risks in pediatric patients with familial Mediterranean fever (FMF). In this study, cardiac autonomic functions were investigated in children with FMF by analyzing HRV and its other probable cardiac effects by echocardiography. We studied 70 pediatric patients with FMF and 50 healthy controls. The time-domain parameters of HRV were compared between the FMF and control groups. SDNN (standard deviation of all NN intervals) was significantly decreased in patients with FMF as compared to control subjects. The other time-domain parameters of HRV and the frequency-domain parameters of HRV were similar in both groups. Frequency-dependent HRV parameters were similar in both groups, as were conventional echocardiographic parameters. HRV is a convenient and reliable technique for evaluation of autonomic functions. There are only a few studies on the assessment of autonomic functions by means of HRV in adult FMF patients but not in pediatric patients. Further studies are required to assess whether there is autonomic dysfunction in children with FMF.

Genetic polymorphisms of paraoxonase1 192 and glutathione peroxidase1 197 enzymes in familial Mediterranean fever

Familial Mediterranean fever (FMF) is an autosomal recessive disorder and is the most frequent of the periodic febrile inflammatory syndromes. The pathogenesis of the disease is not completely understood, even though the FMF gene has been identified. Oxidative stress and inflammation may play a role in the pathogenesis of FMF. We investigated gene polymorphisms of the antioxidative enzymes, glutathione peroxidase (GPX) and paraoxonase (PON) in FMF patients, and possible associations with FMF pathogenesis. Sixty FMF patients during an attack-free period and 51 healthy children as the control group were included in our study. PON1 Q/R192 and GPX1 Pro197Leu gene polymorphisms were assayed. Blood urea nitrogen, creatinine and serum lipid profile were also measured. PON1 Q/R192 genotype distribution was 52% QQ, 46% QR and 2% RR in the FMF group and 45% QQ, 45% QR and 10% RR in the control group (P>0.05). GPX1 Pro197Leu genotype distribution was 28% PP, 57% PL, 15% LL in the FMF group and 18% PP, 53% PL, 29% LL in the control group (P>0.05). Blood urea nitrogen, serum creatinine, lipid levels, and the distribution of PON1 Q/R192 and GPX1 Pro197Leu genotypes were similar in the two groups. We conclude that the PON1 Q/R192 and GPX1 Pro197Leu gene polymorphisms are not important risk factors in the development of FMF. However, larger studies are warranted to validate these conclusions.

Effects of different Familial Mediterranean Fever gene mutations and in vitro Colchicine treatment on Peripheral Blood Mononuclear Cells production of IL-6

Rationale: We wanted to study the effects of Familial Mediterranean Fever (FMF) genetic mutations in Northern Jordan population and in vitro Colchicine treatment on the peripheral blood mononuclear cells (PBMN) production of IL-6 as a marker of disease activity. Methods: - 17 FMF patients and 9 controls were studied. (4 patients had exon 10 mutations only (M680I and V726A), 5 patients had exon 2 mutations (R202Q and E148Q) only and 8 patients with both exon mutations (compound homozygous or heterozygous M694V and R202Q). PBMN cells were incubated with Lipopolysaccharide at 100ng/ml or colchicine 10 ng/ml alone or both. Results: The results showed higher IL-6 levels in the FMF group than control for all treatment modalities, (108.97 vs. 56.49 ng/ml for unstimulated cells) with the highest levels when both exons are involved. Exon 10 mutations were associated with a higher IL-6 level than exon 2 mutations only. Exon 2 mutations alone also were associated with a higher than control IL-6 levels suggesting that it is not a polymorphism phenomenon and is involved in the pathogenesis. In vitro Colchicine treatment caused an increase in the production of IL-6 - although not as high as with LPS - for all groups. Conclusions: Mutations occurring in exon 10 are more significant than mutations occurring in exon 2, although both are contributing to the disease. However colchicine was associated with a paradoxical increase in IL-6 levels. This observation needs confirmation with different colchicine levels in the culture medium and warrants thinking about its exact mechanism of action. DOI: http://dx.doi.org/10.3329/bjms.v12i4.16659Bangladesh Journal of Medical Science Vol. 12 No. 04 October ’13 Page 370-377

Determination of hearing levels in patients with Familial Mediterranean Fever

ObjectiveFamilial Mediterranean Fever is the most common congenital, periodic fever condition that affects over 100,000 people worldwide. In the literature, there is limited number of studies about hearing levels in children with Familial Mediterranean Fever. In the present study, we aimed to investigate hearing levels and cochlear functions by using Distortion product Otoacoustic Emission and High Frequency Audiometry (250–20,000Hz) in pediatric patients with Familial Mediterranean Fever. MethodsThe study included 62 children with Familial Mediterranean Fever and 27 healthy children with similar age and gender. After otoscopic examination, both groups underwent audiological evaluation including High Frequency Audiometry (250–20,000Hz) and Distortion product Otoacoustic Emissions. The results obtained were assessed among groups. In addition, these results were compared regarding colchicine use, age at the onset of disease and duration of the diseases in the Familial Mediterranean Fever group. ResultsOf the Familial Mediterranean Fever patients, 93.5% were on colchicine therapy and mean duration of colchicine use was 19.9±13.9 months. The mean age at diagnosis was 6.57±2.86 years (min–max: 2–14) and mean duration of disease was 23±17 months (min–max: 6–84). Pure tone audiometry values, and hearing levels between 9000 and 20,000Hz were similar and within normal range in both groups. The Distortion product Otoacoustic Emissions responses at the frequencies of 1020, 2040, 3000, 4080 and 5040Hz were similar for both groups. ConclusionTo the best of our knowledge, this is the first study evaluating hearing levels at the frequencies of 18kHz and 20kHz in children with Familial Mediterranean Fever in the literature. In children with Familial Mediterranean Fever, Pure tone audiometry values, hearing values obtained at all frequencies from 250 to 20,000Hz, and Distortion product Otoacoustic Emissions levels were within normal range. Furthermore, hearing levels were found to be similar to those in healthy children.

Assessment of ovarian reserve based on hormonal parameters, ovarian volume, and antral follicle count in women with familial Mediterranean fever

ObjectiveTo evaluate ovarian reserve in women with familial Mediterranean fever (FMF). Study designThirty women with FMF (20–29 years) and thirty healthy controls (20–29 years) were admitted to this study. Basal serum levels of follicle-stimulating hormone (FSH), oestradiol (E2), luteinizing hormone (LH) and inhibin B were measured on cycle day 3. All participants underwent transvaginal ultrasonographic examination on the third day of their menstrual cycle for the determination of ovarian volume (OV) and total antral follicle count (AFC). ResultsWomen with FMF had significantly higher concentrations of FSH, LH and E2 than healthy controls. Total AFC was significantly lower in women with FMF than in healthy controls. OV was also lower in the FMF group but there was no statistically significant difference in OV between the groups. Age was negatively associated with FSH and LH. Inhibin B was found to be negatively correlated with LH and OV. ConclusionsIn this preliminary study, the first in FMF patients, we found that ovarian reserve was reduced in women with FMF compared with healthy controls. FMF may affect the ovarian reserve but the mechanism of this effect is unclear.

THU0458 MPV and RDW: Subclinical Inflammation Markers in Attack-Free Familial Mediterranean Fever (FMF) Patients

ObjectivesMean platelet volume (MPV) and red cell distribution width (RDW), as a marker of inflammation, have an important role in several chronic inflammatory disorders like familial Mediterranean fever (FMF). Many...

Evaluation of the mean platelet volume in secondary amyloidosis due to familial Mediterranean fever

Familial Mediterranean fever (FMF) is an inflammatory disorder that is leading cause of secondary amyloidosis (AA). This study was designed to investigate the level of mean platelet volume (MPV) in AA. Seventy-four FMF, 29 AA patients and 180 healthy controls, were included. There was no significant difference between the cases in terms of sex and age. MPV levels were measured in all groups. In the FMF group, MPV level was significantly higher when compared to the control group. MPV level was significantly lower in AA group in comparison with the FMF and healthy control groups. In summary, our present study showed low MPV values in AA due to FMF.

Oral health and oral quality of life in inactive patients with familial Mediterranean fever without amyloidosis.

The aim of this study was to investigate oral and general health-related quality of life (QoL) in patients with familial Mediterranean fever (FMF) disease. In this cross-sectional study, 45 patients with FMF, 50 age- and sex-matched healthy controls (HC), and 50 patients with Behçet's disease (BD) as the disease control group were included. FMF disease activity was evaluated by using the FMF-severity score, as well as with erythrocyte sedimentation rate (ESR), and serum C-reactive protein and fibrinogen levels. Oral health-related QoL and general QoL were evaluated using oral health impact profile-14 (OHIP-14) and Medical Outcomes Short-Form Health Survey Questionnaire 36 (SF-36), respectively. Only the numbers of extracted teeth (4.13±4.72 vs. 1.55±3.6) and filled teeth (2.33±3.19 vs. 0.66±1.46) were significantly higher in FMF group compared to HC group (p=0.005 and p=0.013, respectively). OHIP-14 score was significantly higher in FMF and BD groups compared to HC group. In FMF patients, OHIP-14 score was positively correlated with the number of extracted teeth (r=0.38, p=0.010), while the number of carious teeth was positively correlated with ESR (r=0.43, p=0.003). When FMF patients were sub-classified according to disease severity, no significant difference was observed with respect to oral health status. In patients with FMF, some of the parameters of oral health status were found to be worse compared to HC group. Tooth loss appears to be to be a critical factor contributing to impaired oral QoL. In general, oral health status in FMF patients is better than in BD patients.

Mortality risk factors associated with familial Mediterranean fever among a cohort of 1.25 million adolescents

ObjectiveThere are limited data on long-term comorbidities and mortality among patients with familial Mediterranean fever (FMF). Our objective was to evaluate comorbidities and death rates among individuals with FMF.MethodsWe studied...

Exertional muscle pain in familial Mediterranean fever patients evaluated by MRI and 31P magnetic resonance spectroscopy

To evaluate the effect of physical activity on the structural, morphological, and metabolic characteristics of the gastrocnemius muscle in familial Mediterranean fever (FMF) patients, utilizing quantitative (31)P magnetic resonance spectroscopy (MRS), in order to elucidate the mechanism of their exertional leg pain. Eleven FMF patients suffering from exertional leg pain (eight male, three female; mean age 33 years) and six healthy individuals (three male, three female; mean age 39 years) constituted the control group. All of the participants underwent magnetic resonance imaging (MRI) and non-selective (31)P MRS (3T) of the leg muscles before and after graded exercise on a treadmill. Phosphocreatine (PCr):inorganic phosphate (Pi), PCr:adenosine triphosphate (ATP) ratios and the intracellular pH of the leg muscles were measured using (31)P MRS. For both groups, normal muscle mass with no signal alterations was observed on the MRI images after exercise. The normal range of pre- and post- exercise MRS muscle parameters was observed in both groups. However, the intracellular pH post-exercise, was significantly higher (less acidic) in the FMF group compared to the control group [pH (FMF)=7.03±0.02; pH (control) 7.00±0.02; p<0.0006]. The finding of a less prominent, post-exercise acidification of the gastrocnemius muscle in this FMF patient group suggests a forme fruste of glycogenosis. This preliminary observation should be further investigated in a future, larger-scale study.

QT interval variability in familial Mediterranean fever: a study in colchicine-responsive and colchicine-resistant patients

The association between familial Mediterranean fever (FMF), early atherosclerosis, and electrocardiographic markers for arrhythmias remains controversial. There are conflicting results as to the occurrence of high QT dispersion in FMF. The aim of the present study was to further investigate repolarization dynamics and other repolarization-associated pro-arrhythmogenic markers in FMF patients. To explore repolarization in FMF, patients who responded well to colchicine and patients who had not responded to colchicine, yet were amyloidosis-free, were included. We aimed to evaluate whether increased inflammatory burden, a characteristic of non-responsive patients, was specifically associated with abnormal repolarization. Included in the study were 53 FMF patients (27 colchicine non-responders) and 53 age- and sex-matched control subjects. Electrocardiograms were performed under strict standards. QT variability parameters were computed with custom-made computer software. No significant difference in any of the QT dynamic parameters was found in either FMF group compared with the healthy controls. Mean values of QT variability index, regardless of colchicine response, were similar to previously published results for healthy persons. In conclusion, patients with FMF who are continuously treated with colchicine and have not developed amyloidosis, regardless of their clinical response, have normal QT variability parameters, indicating normal repolarization dynamics and suggesting no increased risk of repolarization-associated cardiac arrhythmias.

Cephalometric evaluation of children with familial Mediterranean fever

To test the null hypothesis that no differences exist in craniofacial morphology between patients with familial Mediterranean fever (FMF) and the healthy population. Standardized lateral cephalograms of 32 FMF patients (mean age, 11.50 ± 2.72 years) and 32 healthy controls (mean age, 11.86 ± 2.19 years) were obtained. Cranial and dentofacial parameters were measured using a cephalometric analysis program (Nemoceph Imaging Cephalometric and Tracing Software S.L., Spain). All statistical analyses were conducted using SPSS version 17.0.0 (SPSS Inc., Chicago, Ill). Descriptive statistics were calculated for all measurements, and the independent t-test was used to evaluate intergroup differences. The ANB angle was significantly greater in the FMF group (P < .05). Differences in SNA and SNB angles were insignificant. Anterior (P < .001) and posterior (P < .05) face heights were significantly shorter in the FMF group. Mandibular body length (P < .001) and condylion to gnathion (P < .05) measurements were significantly shorter in the FMF group. The upper lip was more protrusive in the FMF group (P < .05). U1-NA (mm; P < .001) and L1-NB (mm; P < .05) measurements were significantly shorter in the FMF group. The hypothesis is rejected. Significant differences exist between the craniofacial morphology of patients with FMF and the healthy population.

Myalgia as a symptom of familial Mediterranean fever in children

We read the article entitled Familial Mediterranean fever gene mutation frequencies and genotype–phenotype correlations in the Aegean region of Turkey prepared by Ozalkaya et al. [1]. The results will be more rational while describing the characteristics of an inherited disease in a certain geographic region, if the data obtained from all or near all of the patients in that region is given. As being another center in the Aegean Region, serving children with familial Mediterranean fever (FMF), we compared our results with those of the above study and aimed to evaluate their consistency. There were 172 patients (M/F: 89/83) being followed up in our center with the diagnosis of FMF based on Tel Hashomer criteria. The mean ages at the onset of symptoms and at the time of diagnosis were months (1–292) and 115 § 63 months (2–612), respectively. Clinical features of the patients are shown in Table 1. MEFV gene analysis including 12 most frequent mutations seen in Turkish people was performed in 84 patients. The results are shown in Table 2. Most frequent mutation was M694V that was present in 60 (71.4%) patients. Three cases with amyloidosis had MEVF gene analysis; two cases were homozygous and one case was heterozygous for M694V mutation. There were 6 patients with none of the twelve mutations screened. The data of our cases from the same geographic region including the mean age of the patients at the diagnosis and at onset of the symptom, frequency of symptoms except for myalgia and genotypes of the patients were found similar to those described in the study of Ozalkaya et al. Although from the same region, myalgia was signiWcantly more frequent among our patients than those in the study of Ozalkaya et al. They categorized their patients due to reliability of diagnosis as deWnitive, probable and suspicious FMF groups. Myalgia frequency was reported to be 9, 7.8 and 2.4% in these subgroups, respectively, the diVerence among the groups being not statistically signiWcant. The rate of myalgia in their group was 6.1% in total, while 20.3% of our patients had myalgia [2–4]. Those patients with protracted febrile myalgia presented to our clinic mostly during the spring months, and their ASO levels were high [2, 3]. Most cases with myalgia were homozygous or compound heterozygous for M694V mutation, while only one case was homozygous for E148Q [2, 5]. One of the patients with myalgia had also amyloidosis and osteopoikilosis and he was transplanted for end stage renal disease [6].

Immunoglobulin Light Chain Levels Can Be Used to Determine Disease Stage in Children with Juvenile Idiopathic Arthritis

Patients with some inflammatory diseases have been shown to have increased levels of immunoglobulin light chains. In this study, we measured the concentrations of immunoglobulin kappa and lambda light chains in sera of patients with juvenile idiopathic arthritis (JIA) (study group), familial mediterranean fever (FMF) (disease control group) and in healthy children. Our aim was to compare immunoglobulin light chain levels with other well-known markers of inflammation, such as the erythrocyte sedimentation rate (ESR) and the acute phase reactants (APRs), serum amyloid A (SAA) and C-reactive protein (CRP), to find out if immunoglobulin light chain determinations have any discriminating value in the follow-up of these patients. ESR, CRP, SAA, kappa and lambda chain levels and lambda/IgG ratio showed a statistically significant difference between active and remission stages in JIA patients. Kappa correlated very well with SAA and ESR in both stages. On the other hand, lambda correlated with SAA and ESR only in the remission period. There was no significant difference in kappa and lambda chain levels between active and remission stages in FMF patients. In addition, kappa and lambda chain concentrations showed no correlation with other markers of inflammation and immunoglobulin levels neither in entire FMF group nor in different subgroups with respect to clinical status. Immunoglobulin light chains kappa and lambda as well as levels of three markers of inflammation were found to be significantly higher in JIA patients who were in the active stage of disease when compared to data of healthy children Ig light chains especially kappa chain concentrations are helpful to determine disease stage in JIA patients but with our current data, they do not exhibit superiority to any of the classical tests for inflammation.

Assessment of heart rate recovery index in patients with familial Mediterranean fever

Heart rate recovery after exercise is a function of vagal reactivation, and its impairment is an independent prognostic indicator for cardiovascular and all-cause mortality. The aim of our study was to evaluate heart rate recovery in patients with familial Mediterranean fever (FMF). The study population included 38 patients with FMF (14 men; mean age, 36.2 ± 12.1 years, and mean disease duration = 11.3 ± 6.5 years) and 35 healthy control subjects (12 men; mean age = 34.1 ± 9.9 years). Basal electrocardiography, echocardiography, and treadmill exercise testing were performed in all patients and control participants. The heart rate recovery index was defined as the reduction in the heart rate from the rate at peak exercise to the rate 1st-minute (HRR(1)), 2nd-minute (HRR(2)), 3rd-minute (HRR(3)), and 5th-minute (HRR(5)) after the cessation of exercise stress testing. There are significant differences in HRR(1) and HRR(2) indices between patients with FMF and control group (26.4 ± 7.4 vs. 35.0 ± 8.0; P = 0.001 and 47.3 ± 11.8 vs. 54.8 ± 10.3; P = 0.002, respectively). Similarly, HRR(3) and HRR(5) indices of the recovery period were lower in patients with FMF, when compared with indices in the control group (56.0 ± 14.0 vs. 63.7 ± 11.2; P = 0.01 and 64.1 ± 14.7 vs. 71.5 ± 12.7; P = 0.02, respectively). There were also remarkably positive correlations between the disease duration and HRR(1) (r = 0.31, P = 0.02), and HRR(2) (r = 0.26, P = 0.04). The heart rate recovery index impaired in patients with FMF compared to control subjects. When the prognostic significance of the heart rate recovery index is considered, a useful, simple, and noninvasive test may be clinically helpful in the recognition of high-risk patients with FMF.

Familial Mediterranean fever gene mutation frequencies and genotype–phenotype correlations in the Aegean region of Turkey

Familial Mediterranean fever (FMF) is a disease characterized by recurrent, self-limiting fever and serositis and caused by altered pyrin due to mutated MEFV gene. The aim of this study was to investigate clinical manifestations and MEFV mutations among patients with FMF and healthy controls in the Aegean region of Turkey. This study included 308 patients and 164 healthy controls. Patients were divided into three groups according to Tel-Hashomer criteria; definitive, probable, and suspicious. Among the patients, 146 were women (47.4%) and 162 were men (52.6%). The mean age (±SD) of the patients at the diagnosis was 9.6±3.95 (range 0.5-18). The mean age (±SD) at onset of the symptom was 6.2±3.95 (range 1-18). Symptoms were seen earlier onset in definitive group than the suspicious group in our cohort (4.7±3.9 years, 6.6±3.9 years, respectively; P=0.001). Clinical features were abdominal pain (83.1%), fever (55%), arthritis (17.1%), myalgia (4.5%), pleuritis (10%), and erysipelas-like erythema (7.7%). Fever, arthralgia, arthritis, chest pain, and amyloidosis were found statistically significant more in definitive group than suspicious group (P<0.001, P<0.001, P<0.001, P<0.05, and P<0.001, respectively). MEFV gene mutations were identified in 199 patients (64.6%). The most commonly encountered MEFV mutation among the patients was M694V homozygote (25%). M694V homozygous mutation was found most frequently in definitive FMF group than other groups (49, 9, 8.9%, respectively). To our knowledge that FMF should be suspected in the case of non-specific but recurrent attacks of serositis and high fever, and molecular analysis should be performed in order to make diagnosis of FMF.

Depression and anxiety in children and adolescents with familial Mediterranean fever

Familial Mediterranean fever (FMF) is the most common autoinflammatory disease which requires a lifelong treatment. The aim of this study was to evaluate the depression and anxiety in pediatric FMF patients. The Children's Depression Inventory and the Screen for Child Anxiety-related Emotional Disorders were the instruments used. Forty-three patients with FMF and 53 healthy controls were compared. Both study and control groups were divided into two age groups, 7-12 and 13-18 years. The depression scores of patients with FMF were significantly higher than their healthy peers (p = 0.001). However, there was no significant difference between patients with FMF and control group regarding the anxiety scores (p = 0.78). The disease duration was not significantly correlated with depression and anxiety scores. There was a significant correlation between depression score and FMF severity score (p = 0.01). The mean depression and anxiety scores of the FMF patients were positively correlated with the number of attacks (p = 0.000 and p = 0.001, respectively).This study suggested that patients with FMF were considerably more depressed than their healthy peers and that the depression scores were negatively affected from disease severity score and number of attacks. Psychosocial assessment of children with FMF has potential clinical implications and individualized counseling and interventions are needed.

Heart rate variability in familial Mediterranean fever

Familial Mediterranean fever (FMF) is a hereditary disease, characterized by recurrent episodes of fever and polyserositis. Heart rate variability (HRV) is a powerful, simple and reliable technique to evaluate autonomic nervous system function. Previous studies of physiologic parameters during tilt-test have suggested that patients with FMF have abnormal cardiovascular reactivity and occult dysautonomia. Prompted by these findings, the present study sought to evaluate HRV in patients with FMF, at rest and in the standing position. The study sample included 34 patients with FMF and 34 sex- and age-matched control subjects. All underwent electrocardiography according to strict criteria. HRV parameters were computed with custom-made software. There was no significant difference in HRV parameters, in either the supine or standing position, between the FMF and control groups. In both groups, the upright position was associated with a significant decrease, when compared with the supine position, in maximal RR interval, minimal RR, average RR, root square of successive differences in RR interval, number of intervals differing by >50 ms from preceding interval (NN50), NN50 divided by total number of intervals (pNN50) and high-frequency components as well as a significant increase in average heart rate, very low frequency or low-frequency components, low-frequency/high-frequency components ratio and total power. In conclusion, patients with FMF who are continuously treated with low-dose colchicine have not developed amyloidosis and have normal HRV parameters in the supine and upright position. Further investigation of occult dysautonomia in FMF is needed.

Demographic, clinical and mutational characteristics of Turkish familial Mediterranean fever patients: results of a single center in Central Anatolia

Clinical and genetic findings of familial Mediterranean fever (FMF) may be variable in different populations. Environmental factors may also affect phenotypic features of FMF. In this study, we investigated demographic, clinical and mutational features of FMF patients who were treated in a single reference hospital in Turkey. Two hundred and sixty patients (169 females, 91 males, mean age 30.44 +/- 10.29 years) were included in this study. All patients were evaluated regarding MEFV gene mutations. The mean age of disease onset was 17.21 +/- 8.66 years (range 2-40 years). The mean duration between the disease onset and diagnosis was 9.39 +/- 8.92 years. Seventy percent of patients had symptoms before 20 years of age (early onset FMF). Arthritis and erysipelas like erythema (ELE) were more common, and the mean duration between the disease onset and diagnosis was longer in early onset FMF patients. The frequency of attacks per year, and disease severity score (DSS) was higher in early onset patients. Homozygote mutation of M694V was detected in 37 (20.2%) and 4 (5.2%) patients in early onset FMF and adult onset FMF groups, respectively (p < 0.05). Histological diagnosis of amyloidosis was established in 7 patients (2.7%). The age of disease onset was earlier, and arthritis and ELE were more frequent, and DSS was higher in patients with M694V/M694V mutation. In conclusion, mean delay to diagnosis in our FMF population is quite high. Early and adult onset forms may differ regarding some clinical, molecular and prognostic characteristics. Disease activity was higher in patients with homozygote mutation of M694V.