The Evaluation of Health Status of Familial Mediterranean Fever Patients with Homozygous M694V Mutation

Abstract

Aim: Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disorder characterized by recurrent episodes of fever, serositis, and systemic inflammation. The M694V mutation in the MEFV gene is associated with a more severe disease phenotype, including early onset, frequent attacks, and an increased risk of amyloidosis. This study aimed to evaluate the clinical features, comorbidities, and treatment outcomes of FMF patients homozygous for the M694V mutation. Material and Methods: A retrospective analysis was conducted on 183 FMF patients homozygous for the M694V mutation, diagnosed and followed at our hospital between 2014 and 2022. Data on demographics, clinical characteristics, laboratory findings, and treatment modalities were collected. Results: The most common symptoms were abdominal pain (88%), joint pain (78%), and arthritis (46%). Proteinuria and amyloidosis were detected in 22.4% and 7.1% of patients, respectively. The average age of symptom onset was 14.1 years, with a mean annual attack frequency of 2.75. Comorbidities were present in 24% of patients, including spondyloarthritis and inflammatory bowel disease. Colchicine was the mainstay treatment (94.5%), while 21.8% required IL-1 inhibitors. Eight patients (4.4%) died during follow-up, five due to amyloidosis-related complications. Conclusion: M694V homozygous FMF patients exhibit a severe disease presentation associated with this variant with frequent attacks, high amyloidosis risk, and significant comorbidities. While colchicine remains essential, biologics are increasingly used for colchicine-resistant cases. Early diagnosis, individualized treatment, and regular monitoring are crucial to improving patient outcomes.