Pos1191 Genetic and Clinical Heterogeneity in Familial Mediterranean Fever: Unraveling Patterns of Mutations, Symptomatology, and Disease Associations

Background: Familial Mediterranean fever (FMF) is an autoinflammatory genetic disorder that mainly affects people of Mediterranean origin, manifested by recurrent episodes of fever, serositis and synovitis. Typically, the diagnosis of FMF is confirmed when individuals inherit two copies of the mutated MEFV gene, one from each parent. Nevertheless, there is a possibility for an individual to possess only one mutated copy, resulting in the manifestation of certain symptoms. Objectives: 1. To determine the number of patients exhibiting clinical manifestations of FMF with inconclusive result of genetic analysis. 2. To determine the number of FMF patients with isolated joint syndrome. 3. To examine the prevalence of sacroiliitis and explore its association with the carriage of HLA-B27. 4. To determine the association between arthritis and specific mutations of MEFV. Methods: 184 patients were included in the study (83 males/45.1%/, 101 females/54.9%/, mean age 31.57 ± 11.68 years). The anamnestic and treatment data were obtained. CBC, urinalysis, serum creatinine, CRP, SAA were determined, x-ray examination and ultrasonography of joints, molecular-genetic analysis of MEFV-mutations and spine MRI were performed. Some data are introduced as odds ratios (OR) with 95% confidence interval (CI). The results were considered significant when p<0.05. Results: Among the participants, the mutations were determined in 182 patients (98.9%), while 2 (1.08%) patients didn't have mutations, but presented with typical clinical symptoms. The distribution of mutation types was as follows: 24 individuals (13%) were homozygous, 83 (45.1%) - compound heterozygous, and 75 (40.8%) - simple heterozygous. Among patients displaying clinical manifestations 74 (40.2%) had recurrent attacks of peritonitis, 9 (4.9%) – pleuritis, 50 (27.2%) presented with synovitis and erysipeloid rash, 53 (28.8%) had mixed pattern. Additionally, 25 patients presented with the signs of spondyloarthritis, while only 7 of them were carriers of HLA-B27. The most prevalent mutations were M694 – in 110 (59.8%), V726A – in 62 (33.7%), M680I – in 36 (19.6%) and E148 Q - in 31 (16.8%) patients respectively. The most frequent mutations observed in homozygotes were M694V and V726A. In the cases of inconclusive genetic analysis 73 patients were simple heterozygous, and 2 patients didn't have mutations, but presented with typical clinical symptoms. In this group of patients 30 (40 %) exhibited peritonitis, 28 (37.33 %) - joint syndrome and erysipeloid rash, 13 (17.33%) - mixed manifestation (peritonitis and pleurisy), 4 (5.33%) - pleuritis, and 9 (12%) patients had sacroiliitis. In total, 61 (33.2%) patients had joint syndrome, 50 of which had isolated joint syndrome and 14 (28%) had accompanying sacroiliitis. Sacroiliitis was found in 25 patients, in 2 patients it was accompanied with the abdominal syndrome, 2 patients had mixed pattern. Among the patients with joint syndrome, 4 individuals had homozygous, 18 - compound heterozygous, and 28 - simple heterozygous genotype․ Among the patients with articular syndrome, the most frequent mutations were M694V – in 36 (59%), V726A – in 15 (24.59%), M680 – in 6 (9.83%), and E148Q - in 5 (8.19%) patients. We identified a positive association between the carriage of the M694V mutation and the occurrence of joint syndrome (OR/95% CI/= 1.99/1.03-3.8/, p<0.05). A negative association between the development of joint syndrome and the carriage of the M680I mutation was found (OR/95% CI/= 0.34/0.13-0.86/, p<0.05). Conclusion: The molecular genetic testing of the MEFV gene plays a significant role in the diagnosis of FMF. However, it is crucial to highlight the importance of clinical criteria, for instance Tel-Hashomer criteria, for the proper diagnosis of FMF, as the genetic testing may be inconclusive. Often the onset of FMF is expressed by joint syndrome and erysipeloid rash, sometimes accompanied with signs of spondyloarthritis. In such cases, a rheumatologist is primarily observing the patient. In all cases of undifferentiated arthritis/spondyloarthritis, it is essential to consider the patient's ethnicity and include FMF in diagnostic algorithm. REFERENCES: NIL.Acknowledgements: NIL. Disclosure of Interests: None declared.