Clinical and genetic characteristics of adult patients with familial Mediterranean fever at a German tertiary referral centre

OBJECTIVE: To characterise the clinical and genetic profile of adult familial Mediterranean fever (FMF) patients at a German tertiary referral centre and examine genotype-phenotype associations. METHODS: In this prospective single-centre registry study (October 2019-March 2021), 95 adult FMF patients at University Hospital Tübingen were evaluated using structured questionnaires and medical record review. All patients had a pre-existing clinical diagnosis of FMF based on the Tel Hashomer and/or Eurofever/PRINTO criteria. Demographic data, clinical manifestations, treatment, and MEFV mutations were analysed. Patients were stratified by mutation status (homozygous M694V, heterozygous/compound-heterozygous M694V, other mutations). Statistical analyses included the Fisher-Freeman-Halton exact test and ANOVA. Variants were classified according to the INSAID consensus classification; R202Q was treated as a benign polymorphism. All subgroup comparisons were exploratory and were not corrected for multiple testing. RESULTS: Median age was 36 years, with median symptom onset at 10 years. Most patients were of Turkish origin (74.7%), and 59.6% reported a family history of FMF. Common manifestations included abdominal pain (90.5%), arthralgia/arthritis (75.8%), fever (66.3%), and chest pain (52.6%). Colchicine was used in 96.8% of patients, while 38.3% received biologic therapy, a figure influenced by concurrent participation in a tocilizumab trial at our centre. MEFV analysis had been performed in 91 of the 95 patients (95.8%); among these, at least one MEFV variant was detected in 87 (95.6%), with M694V being the most frequent variant (61.5%). Homozygous M694V patients showed earlier disease onset (nominal p = 0.02) and higher rates of arthralgia/arthritis (nominal p = 0.035). Amyloidosis occurred in one patient with homozygous M694V. CONCLUSION: This cohort demonstrates typical FMF features with a predominance of the M694V mutation. Homozygosity for M694V is associated with earlier disease onset and increased musculoskeletal involvement. Subgroup findings are exploratory and require confirmation in independent cohorts.