000540 - Amyloidosis in patients with Familial Mediterranean fever in Slovakia

Familial Mediterranean fever (FMF) is the most common monogenic periodic fever syndrome. Its prevalence in Slovakia is 1:48,224. Clinically, it manifests as recurrent episodes of fever accompanied by abdominal, joint, or chest pain, along with elevated acute-phase reactants during attacks. Patients are asymptomatic between attacks. The most serious complication is the development of organ (AA) amyloidosis.

This is the retrospective clinical study of clinical manifestation, laboratory findings, and genetic background of FMF patients with organ amyloidosis. Molecular-genetic testing using massive parallel sequencing of the clinical exome with a virtual panel of genes associated with amyloidosis and inborn errors of immunity including other genes associated with autoinflammation was performed in studied patients.

We follow up 6 FMF patients with organ amyloidosis what represents 5.3% of patients from Slovakian national FMF cohort. Five patients exhibited symptoms of periodic fever and serositis, while one patient lacked periodic fever, consistent with FMF type 2 (amyloidosis only) with involvement of the kidneys, large intestine, and peripheral nervous system. All patients responded well to colchicine therapy, achieving normalisation of SAA levels and renal parameters (creatinine), a reduction in proteinuria, and a decrease in the protein-to-creatinine ratio. Pathogenic or likely pathogenic variants in MEFV gene were identified in all patients. The four observed genotypes were M694V/M694V; M694V; K695R, and M694V/E148Q.

The most severe complication of FMF is the development of organ amyloidosis. Timely and targeted therapy can prevent this complication. When evaluating the results of molecular-genetic testing, it is essential to consider both family and personal medical history, with assessment of the presence of risk manifestations. The genotype’s risk for developing organ amyloidosis should also be evaluated, which is important even in asymptomatic individuals (possibility of FMF type 2).