988 - Demographic and Genetic Results From the EUROFEVERS/EUROTRAPS Consortia in the Largest Series of Patients with TRAPS Yet Reported

Monday, November 7, 2011: 9:00 AM-6:00 PM
Hall F2 - Poster Hall (McCormick Place West)
Helen J. Lachmann1, Antonella Meini2, Isabelle Touitou3, Laura Obici4, Martina Finetti5, Kirsten Minden6, Luca Cantarini7, Marine Desjonqueres8, Joost Frenkel9, Isabelle Kone-Paut10, Olga Vougiouka11, Maria Jesus Rua Elorduy12, Nicola Ruperto13, Patricia Woo1 and Marco Gattorno14, 1University College London Medical School, London, United Kingdom, 2Dipartimento di Pediatria, University of Brescia, Brescia, Italy, 3CHU Montpellier - Hôpital Arnaud de Villeneuve, Montpellier, France, 4IRCCS Policlinico S. Matteo, Pavia, Italy, 5IRCCS Istituto G. Gaslini, Genova, Italy, 6Charite, Berlin, Germany, 7Policlinico le Scotte, Sienna, Italy, 8Hopital Femme Mere Enfant, Groupement Hospitalier Est, Lyon, France, 9University Medical Center Utrecht, Utrecht, Netherlands, 10CHU Le Kremlin Bicetre, Paris, France, 11P. A. Kyriakou Childrens Hospital of Athens University, Athens, Greece, 12Hospital de Cruces, Barakaldo, Spain, 13Paediatric Rheumatology International Trials Organisation – IRCCS [PRINTO], Genova, Italy, 14G Gaslini Institute, Genoa, Italy
Presentation Number: 988

Background/Purpose: The TNF receptor associated periodic syndrome (TRAPS) is an autosomal dominant autoinflammatory syndrome due to mutations in the TNFRSF1A gene. It is associated with severe morbidity and increased mortality due a high risk of AA amyloidosis.  The estimated prevalence is 1 per million and experience has previously been limited to small series.

Method: The Eurofever/Eurotraps consortia (funded by the European Union) have developed a common web-based registry for all autoinflammatory diseases . The registry is accessed from the member area of the PRINTO web-site (www.printo.it/eurofever) and is available to all interested specialists physicians.

Result: 178 patients with clinical disease and a TNFRSF1A mutation were identified from 11 countries. The series included cases with 66 different mutations and 2 low penetrance mutations/polymorphisms, R92Q and P46L. Of the 66 mutations 8 (12%) were reported in more than 1 unrelated individual or kindred; 19 (29%) mutations affected a cysteine residue and of these 5 (26%) were seen in at least 2 unrelated patients. The T50M mutation was the most widespread and was found in 5 families originating from 5 different European countries. More than 1 disease associated mutation was identified at 7 sites, including 5 cysteine residues. In total of the 122 patients with a TNFRSF1A mutation: 68 (60.7%) reported a family history of similar symptoms; 58 (51.8%) were male; 105 (93.8%) were of Caucasian ethnicity and the mean age at symptom onset was 7.6 yrs (range: neonatal to 49 yrs). Of note in 10 patients (9%) the first symptoms developed after the age of 30 yrs. The 59 patients with R92Q polymorphism were 98% Caucasian, 45.8% male and 17% gave a family history of similar inflammatory disease. They presented at an average age of 10 yrs (range: neonatal to 52.6 yrs). The 7 patients with the P46L polymorphism included 2 patients of African ancestry, 1 Turk and a Gulf Arab, they presented at an average age of 16.6 yrs (range: 2.5 to 66.3 yrs) and 2 of them reported that other family members had similar disease.

Conclusion: The EUROFEVERS/EUROTRAPS consortia have collected data on 178 mutation positive TRAPS patients from 11 countries constituting the most extensive clinical series to date. The patients were largely contributed by European centres which may explain the dominance of Caucasian ethnicity. It confirms that TRAPS usually presents in childhood with a median age at presentation of less than 5 yrs but 9% of patients present well into adult life. 60% of patients report a family history of disease and most reported kindreds are small and mutations are family specific. Mutations affecting cysteine residues in extracellular domains are over represented but the most widespread disease causing mutation is T50M. Symptomatic patients with the well recognised polymorphism of R92Q and P46L make up 38% of the patients and appear to have a later onset of disease symptoms with lower penetrance. The availability of a large patient cohort will facilitates interpretation of the significance of TNFRSF1A mutations/polymorphism and understanding of genotype phenotype correlations.

Keywords: inflammation

Disclosure: H. J. Lachmann, None; A. Meini, None; I. Touitou, None; L. Obici, None; M. Finetti, None; K. Minden, Abbott Immunology Pharmaceuticals, 6 ; L. Cantarini, None; M. Desjonqueres, None; J. Frenkel, None; I. Kone-Paut, None; O. Vougiouka, None; M. J. Rua Elorduy, None; N. Ruperto, None; P. Woo, None; M. Gattorno, None.