BackgroundFamilial Mediterranean fever (FMF) affecting mainly Mediterranean and Middle Eastern populations.is an autosomal recessive inherited inflammatory disease caused by mutations in the Mediterranean fever (MEFV) gene. It is characterized by periodic attacks of fever and inflammation affecting serosal membranes. The most common symptoms of the disease are fever, abdominal pain, arthritis, erysipelas-like erythema, pleuritis, and pericarditis. Patients are usually treated by life-long colchicine, which has been shown to be effective in preventing the attacks of FMF as well as the development of amyloidosis. FMF diagnosis remains often difficult due to the lack of pathognomonic laboratory findings. The definitive clinical classification of FMF is made by Tel Hashomer criteria[1]. Genetic analyzes may support the clinical diagnosis of patients for mutation complications.ObjectivesThis study aimed to not only investigate the contribution of MEFV mutations to FMF diagnosis but also to show whether there is a phenotype–genotype correlation in the same patient population.MethodsWe evaluated 12 MEFV gene mutations screened with a commercial kit based on real-time polymerase chain reaction technique in 1064 adults between January 2016 and November 2021. We were able to interview 208 of 484 people with AAA mutations by telephone. We investigated whether they were diagnosed with FMF according to Tel Hashomer criteria or clinician opinion, and compared their clinical and genetic characteristics. In addition, it was investigated whether there was a colchicine or interleukin-1 inhibitor drugs use report issued for drug fee exemption from the medical records of everyone who underwent genetic analysis, since it assumed the diagnosis of FMF in our country.ResultsAccording to the results of 1064 genetic analysis (484 with MEFV mutation), 228 patients (21.4%) were either still using colchicine with the diagnosis of FMF or had previously used colchicine before IL-1 inhibitor treatment. The rate of giving colchicine with the diagnosis of FMF in patients with MEFV mutation (39.7%) was found to be significantly higher than those without mutation (p<0.001). Of the 208 patients with genetic mutations which we interviewed by telephone, 89 (42.8%) met the Tel Hashomer criteria. The most detected mutations in patients meeting Tel Hashomer criteria were M694V (46,1%), M680I (24,7%), V726A (8,9%), and E148Q (8,9%) respectively. The positive significant associations were found between M694V and M680I homozygous mutations and definite/probable diagnosis according to Tel Hashomer criteria (p=0,001, p=0,021, respectively). A negative correlation was found between E148 heterozygous mutation and diagnosis (p=0,002). When the relation between genetic mutations and clinical findings was examined, it was shown that there was a positive correlation between fever and M694V, and between abdominal pain and M680I (p=0,000, p=0,007, respectively). Patients with the E148Q mutation had significantly less fever and abdominal pain (p=0,028, p=0,017, respectively).ConclusionConsidering that approximately one-fifth of those undergoing genetic analysis are diagnosed with FMF, it can be concluded that unnecessary genetic testing is performed in our hospital. In clinical practice, the precence of MEFV gene mutations M694V and M680I is helpful for FMF diagnosis. E148Q mutation were not been found to be associated with both the diagnosis and the clinical findings. Genetics plays a critical role in confirming the diagnosis, but it should never take the place of a clinical diagnosis. The clinicians should be aware of the indications and limitations of genetic testing and know how to interpret the results.Reference[1]Livneh A, Langevitz P, Zemer D, Zaks N, Kees S, Lidar T, et al. Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum 1997; 40: 1879-85Acknowledgements:NIL.Disclosure of InterestsHikmet Akar: None declared, Dilek Gün Bilgiç: None declared, Özgül Soysal Gündüz Speakers bureau: Amgen, Abbvie, Novartis.
