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).


OBJECTIVE
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.
Department of Paediatric Rheumatology, Children's Hospital, University Duisburg-Essen, Hufelandstr. 55, 45122, Essen, Germany. elke.lainka@uni-due.de
E
E
Lainka
M
M
Bielak
P
P
Lohse
C
C
Timmann
S
S
Stojanov
R
R
von Kries
T
T
Niehues
U
U
Neudorf
D015415:Biomarkers / Q000097:blood; D003598:Cytoskeletal Proteins / Q000235:genetics*; D010505:Familial Mediterranean Fever / Q000175:diagnosis* / Q000208:ethnology* / Q000235:genetics; D005858:Germany / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D009154:Mutation; D011110:Polymorphism, Genetic; D011159:Population Surveillance; D011446:Prospective Studies; D000071198:Pyrin; D014421:Turkey / Q000208:ethnology
D015415:Biomarkers; D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D000071198:Pyrin