Characteristics and outcomes of adult patients with familial Mediterranean fever: Comparison of patients with one versus two pathogenic exon 10 MEFV mutations.

Objective: To describe the main features and outcomes of a large cohort of adult familial Mediterranean fever (FMF) patients with one pathogenic MEFV mutations and compare them to FMF patients displaying 2 pathogenic MEFV mutations.

Methods: In a retrospective single-referential French center cohort of 581 patients with FMF, 178 FMF patients with one pathogenic mutation were retrieved and compared to 403 patients with 2 pathogenic MEFV mutations. The diagnosis of FMF was based on the Eurofever/PRINTO classification criteria for all patients, and they had all been sequenced for MEFV. Patients with M694V/E148Q genotype were also compared to M694V/WT patients.

Results: Compared to FMF patients with 2 pathogenic MEFV mutations, patients with one pathogenic mutation showed significantly higher age at diagnosis and at disease onset (25 vs 10years and 12 vs 5years, P<0.001, respectively), higher personal history (21% vs 5%, P<0.001) or familial history (13% vs 5%, P=0.001) of recurrent aphthous stomatitis (RAS) and higher body mass index (BMI) (24 vs 23kg/m, P<0.05). Conversely, patients with one mutation showed no AA amyloidosis (0 vs 6%, P=0.001) and lower colchicine dosage (P<0.001) than patients with two pathogenic MEFV mutations. These differences remained significant after adjustments for age at disease onset (beginning in childhood or adulthood). No clinical difference was found between patients with M694V/E148Q and M694V/WT.

Conclusion: Adult FMF patients with a single pathogenic MEFV mutation display specific clinical features as well as different evolution compared to patients with 2 pathogenic MEFV mutations.