Evaluation of Children with Familial Mediterranean Fever in South-Eastern Region of Türkiye

Background: Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disorder commonly found in populations from the Mediterranean region, including Turks, Armenians, Arabs, and Jews. It is characterized by recurrent episodes of fever and inflammation, primarily affecting the peritoneum, pleura, and joints. Familial Mediterranean fever is caused by mutations in the MEFV gene, which encodes pyrin, a protein that regulates the inflammatory response. The most common mutations associated with FMF are M694V, M680I, and V726A. These mutations lead to the overproduction of interleukin-1β (IL-1β), triggering the inflammatory episodes that are the hallmark of the disease. Objectives: This study aims to explore the clinical implications of MEFV gene mutations in a cohort of patients diagnosed with FMF and treated with colchicine. The primary objective is to determine the frequency of various MEFV mutations in the patient cohort and examine their association with clinical presentations, such as symptom severity and response to treatment. Methods: A retrospective cohort of 302 patients diagnosed with FMF and undergoing colchicine treatment was examined. Demographic data, clinical symptoms, and genetic mutations were systematically collected and analyzed. Mutation analysis focused on identifying the most common MEFV variants and their potential influence on clinical outcomes. Consanguinity and family history were also considered for their role in FMF genetic predisposition. Results: The study included 157 females and 145 males, with a mean age of 142.60 ± 48.04 months at the time of analysis. The average age of diagnosis was 94 ± 42 months, with no significant differences between genders. Abdominal pain was the most common symptom (90.3%), followed by fever (69.0%) and arthralgia (42.3%). Consanguinity was reported in 35.1% of cases, mainly between first-degree cousins, and 24.5% had a family history of FMF. Genetic analysis revealed that the M694V mutation was the most common homozygous mutation (71.4%), followed by the E148Q mutation as the most frequent heterozygous mutation (37.5%). The compound heterozygous mutation M694V/E148Q was found in 20% of cases. A statistically significant association was found between arthritis and homozygous mutations (P = 0.001) as well as with the M694V mutation (P = 0.004). Homozygous M694V mutations were detected in 16.9% of patients. The findings underscore a strong correlation between the M694V mutation and the development of FMF. Despite the efficacy of colchicine in managing symptoms and preventing complications such as amyloidosis, some patients exhibited treatment resistance, particularly those with arthritis. Conclusions: This study highlights the significant role of MEFV gene mutations, particularly M694V, in the pathogenesis of FMF. It underscores the importance of early diagnosis and the potential for personalized treatment based on genetic findings. While the retrospective design of the study presents limitations, such as selection and information bias, the results provide valuable insights into the clinical and genetic dimensions of FMF. Future studies should build on these findings by using prospective designs and investigating the interaction between genetic and environmental factors in FMF. Expanding the scope of genetic analysis could also lead to the discovery of new mutations, enhancing our understanding of this complex disorder.