Abstract
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 106 person-years in the whole children population and 55 (95 % CI: 46–66) per 106 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.
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Abbreviations
- FMF:
-
Familial Mediterranean fever
- ESPED:
-
German paediatric surveillance unit for rare paediatric diseases
- AID:
-
Autoinflammatory disease
- HRF:
-
Hereditary recurrent fever syndrome
- NSAID:
-
Non-steroidal anti-inflammatory drug
- MEFV:
-
Mediterranean fever
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Acknowledgments
The authors thank the following colleagues for their collaboration:
Clinic-ESPED n = 122:
T. Kallinich (Charité, Berlin) n = 22
I. Földvari (Clinic Eilbeck, Hamburg) n = 11
U. Kruse (University children’s hospital, Essen) n = 10
P. Lankisch (HHU Children’s hospital, Düsseldorf) n = 5
K. Mönkemöller (Children’s hospital, Köln) n = 5
C. Rietschel (Clementine-Children’s hospital, Frankfurt) n = 5
S. Buderus, C. Franz (St. Marien-Hospital, Bonn) n = 4
H. Wittkowski, D. Föll (University children’s hospital, Münster) n = 4
T. Berger (Children’s hospital, Datteln) n = 3
M. Gabriel, B. Markert (Clinical centre, Aschaffenburg) n = 3
E. Lankes, A. Pfünder (Children’s hospital Schwabing, München) n = 3
H. Bachmann, J. Dallmeyer (Hospital Links der Weser, Bremen) n = 2
U. Brand (Clinical centre, Ludwigsburg) n = 2
S. De Negri (Hospital Dritter Orden, München) n = 2
T. Hospach (Olgahospital, Stuttgart) n = 2
J. Kümmerle-Deschner (University children’s hospital, Tübingen) n = 2
K. Minden (HELIOS hospital, Berlin-Buch) n = 2
R. Rossi, J. Rakob (Hospital Neukölln, Berlin) n = 2
S. Wangemann (St. Johannes-Hospital, Duisburg) n = 2
U. Winckelmann, GM. Beron (Dr.-H.-Schmidt-Hospital, Wiesbaden) n = 2
S. Wirth, (HELIOS hospital, Wuppertal) n = 2
F. Zepp (University children’s hospital, Mainz) n = 2
N. Baumgärtner (University children’s hospital, Frankfurt) n = 1
S. Benseler (University children’s hospital, Bonn) n = 1
H. Böhme (Harz-Clinical centre GmbH, Wernigerode) n = 1
P. Conjeevaram (Clinical centre, Offenbach) n = 1
M. Erdmann (Marienkrankenhaus, Papenburg) n = 1
U. Ermer (Hospital St. Elisabeth, Neuburg/Donau) n = 1
S. Fahl (University children’s hospital, Köln) n = 1
G. Ganser (St. Josef-Stift, Sendenhorst) n = 1
K. Huß (LMU Children’s hospital, München) n = 1
B. Kinder (Clinical centre, Neubrandenburg) n = 1
H. Koch (St. Marien-Hospital, Vechta) n = 1
A. Längler (General hospital, Herdecke) n = 1
J. Möller (Clinical centre, Saarbrücken) n = 1
C. Müller (General hospital, Solingen) n = 1
W. Rauh (Mother house of Borromeans, Trier) n = 1
J. Rösler (University children’s hospital, Dresden) n = 1
M. Scharnetzky (Diakonie Hospital, Rotenburg) n = 1
U. Schimmel (Children’s hospital, Hagen) n = 1
P. Schlumberger (University children’s hospital, Marburg) n = 1
L. Schmid (County hospital, Altötting) n = 1
M. Schulze Becking (Clinical centre, Oldenburg) n = 1
J. Spiegler (University children’s hospital Schleswig-Holstein, Lübeck) n = 1
V. Stephan (St. Josef-Hospital, Bochum) n = 1
F.K. Trefz (County Hospital, Reutlingen) n = 1
C. Willaschek (Caritas-Hospital, Bad Mergentheim) n = 1
Laboratory-ESPED n = 544:
S. Burwinkel (Department of Molecular Medicine, Bernhard Nocht Institute for Tropical Medicine, Hamburg) n = 172
H. Ruebsamen (Department of Clinical Chemistry – Großhadern, University of Munich, Munich) n = 108
T. Haverkamp (MVZ Dortmund Dr. Eberhard & Partner, Dortmund) n = 96
G. Wildhardt (Bioscientia Center for Human Genetics, Ingelheim) n = 40
T. Trosch, D. Gläser (Genetics, Dr. Mehnert & Partner, Neu-Ulm) n = 35
C. Aulehla-Scholz (Institute of Clinical Genetics, Olgahospital, Stuttgart) n = 25
S. Kleinle (synlab MVZ Human Genetics München GmbH, München) n = 23
R. Maiwald (MVZ for Laboratory Medicine, Mönchengladbach) n = 18
F. Austrup (Laboratory for Human Genetics, Datteln) n = 7
E. Krasemann (MVZ Lab Fenner & Colleagues, Hamburg) n = 7
C. Meyer-Kleine (Center for Human Genetics, Linden and laboratory Beudt, Frankfurt) n = 4
T. Rogge (Laboratory of the Vivantes-Klinikum Neukölln, Berlin) n = 3
H. Skladny (Center for Human Genetics, Mannheim) n = 2
S. Theil (Institute for Tropical Medicine, University Tübingen, Tübingen) n = 2
H. Gabriel (Center for Human Genetics, Osnabrück) n = 1
W. Schmidt (Laboratory Arndt, Hamburg) n = 1
No cases of W. Heinritz (Institute for applied human genetics and oncogenetics, Leipzig)
The authors thank U. Göbel and B. Heinrich from the ESPED registry. E. Lainka gratefully acknowledges the comments made by O. Weiergräber (Forschungszentrum Jülich, Germany).
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E. Lainka and all coauthors declare that there are no conflicts of interest, relationships, and affiliations relevant to this manuscript.
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Lainka, E., Bielak, M., Lohse, P. et al. Familial Mediterranean fever in Germany: epidemiological, clinical, and genetic characteristics of a pediatric population. Eur J Pediatr 171, 1775–1785 (2012). https://doi.org/10.1007/s00431-012-1803-8
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DOI: https://doi.org/10.1007/s00431-012-1803-8