Prevalence estimation of a rare disease with the French National Rare Disease Registry: example of TNF receptor associated periodic syndrome (TRAPS)

Background rare diseases (RD) have progressively emerged as public health priority in many countries. Epidemiology still presents obstacles and extracting data from public health system remains insufficient. In France, RD database set up in 2013 as Banque Nationale de Données de Maladies Rares (BNDMR). Patients’ information is provided by physician at each consultation and RD are classified according ORPHAcode. We aimed to test the reliability and quality of data for epidemiology by analyzing the data from a rare disease caused by autosomal dominant inheritance and with a univocal genetic diagnosis: TNF-related associated periodic syndrome (TRAPS). Results we extracted data in January 2023. We found 132 patients who fulfilled inclusion criteria and we excluded 31 patients (missing data and duplicates). We analyzed 101 sequences of TNFSRSF1A gene. Pathogenic and likely pathogenic variants were found in 59% of patients, while the remaining 41% should currently be classified as undetermined systemic autoinflammatory disease (USAID). We therefore estimated the minimum prevalence of TRAPS in France: 1/1 343 568. Conclusion In the French National Rare Disease Registry, the quality of data remains a challenge, especially in monogenic diseases where the knowledge of the pathogenicity of variants and the number of gene involved is constantly increasing. Our study suggests that the data exported from the BNDMR needs important data correction to allow reliable epidemiologic studies in these diseases. However, the database seems to be a good tool to identify the centers where RD patients are followed and could be recruited in specific studies after confirmation of the diagnosis.