Familial Mediterranean fever in Germany: epidemiological, clinical, and genetic characteristics of a pediatric population

Familial Mediterranean fever (FMF) is an autoinflammatory disease and belongs to the heterogeneous group of hereditary recurrent fever syndromes (HRFs). Aims : The aims of the study were to determine the incidence of FMF in Germany and to describe the spectrum of pyrin mutations and the clinical characteristics in children. A prospective surveillance of children with HRF including FMF was conducted in Germany during a time period of 3 years by the German paediatric surveillance unit for rare paediatric diseases (ESPED). Monthly inquiries were sent to 370 children’s hospitals (Clinic-ESPED, n1) and to 23 laboratories (Laboratory-ESPED, n2). Inclusion criteria were children ≤16 years of age, disease-associated pyrin mutations, and more than three self-limiting episodes of fever >38.5 °C with increased inflammation markers. In n1, 122 patients with FMF and 225 pyrin mutations were identified. Ninety-two of 122 (75 %) children were of Turkish origin. The minimum incidence of FMF was estimated to be 3 (95 % CI: 2.48–3.54) per 10 6 person-years in the whole children population and 55 (95 % CI: 46–66) per 10 6 person-years in Turkish children living in Germany. N1 U n2 amounted to 593 asymptomatic and symptomatic carriers of 895 mutations (overlap of 73 cases with 134 mutations). p.Met694Val (45 %), p.Met680Ile (14 %), p.Val726Ala (12 %), and p.Glu148Gln (11.5 %) were the most common pyrin mutations. Conclusions : Despite FMF being the most frequent of the HRFs, its incidence in Germany is low. Twenty-five to 50 FMF patients ≤16 years are newly diagnosed per year. The disease is most commonly observed in individuals of Turkish ancestry. Key Messages • The incidence of FMF in Germany is calculated as 3 per 10 6 person-years for the entire children population and as 55 per 10 6 person-years for children of Turkish ancestry. • The pyrin p.Met694Val, p.Met680Ile, p.Val726Ala, and p.Glu148Gln mutations are the prevailing missense mutations. • The awareness of the disease symptoms, especially for children with a migration background, must be increased, and the management of FMF as the most common AID must be improved.