Reducing the diagnostic delay in Antiphospholipid Syndrome over time: a real world observation

Background Antiphospholipid Syndrome (APS) is a rare autoimmune disorder with an estimated prevalence of 40–50 cases per 100.000 persons. Patients suffering from low prevalence diseases are more likely to face diagnostic challenges, given the limited knowledge of most clinicians. The main aim of this study was to investigate the time between symptoms occurrence and the diagnosis of APS patients using the Piedmont and Aosta Valley Rare Disease Registry. Secondly, to evaluate the individual impact of the diagnostic gap by gathering patients’ personal experiences through a self-administered questionnaire. Results Data from the Piedmont and Aosta Valley Rare Disease Registry was used. In addition, personal experiences were analyzed through a self-administered questionnaire. A total of 740 APS patients included in the Piedmont and Aosta Valley Rare Disease Registry were analyzed. Diagnostic delay (as defined by time between symptoms’ occurrence and the diagnosis of APS) was significantly reduced over time. In particular, when comparing the diagnostic delay between patients diagnosed between 1983 and 1999 and patients diagnosed between 2000 and 2015, we found a significant statistical difference (Mann-Whithey U Test; mean rank 1216.6 vs. 1066.9, respectively; p < 0.0001). When analyzing the self-administered questionnaires, patients with a perception of having suffered for a diagnostic delay had a higher prevalence of symptoms suggestive of an autoimmune condition but not highly suggestive of APS (45%), followed by “extra criteria” APS manifestation (30%) and by thrombotic events (25%). The first clinical manifestation of patients who did not have the perception of having suffered a diagnostic delay was thrombotic events (45.5%), followed by autoimmune manifestation not linked to APS (45.5%), and “extra criteria” APS manifestations (9%). Conclusions While the diagnostic delay of APS has been reduced during the last years, the time between symptoms occurrence and the diagnosis of rare diseases still represents a critical issue to be addressed in order to prevent major complications.

A Medical Report Feature for OSSE Rare Disease Registries

Web-based patient registries support clinicians by providing a way to effectively store and process data. Here, we present a new feature for the open-source registry software OSSE: medical reports generated with R Markdown. As part of a rare disease research project, we describe the process from requirements assessment to the current state of technical implementation. The feature offers clinicians the possibility to download customised as well as generic reports from an OSSE rare disease registry.

Use of a rare disease registry for establishing phenotypic classification of previously unassigned GLA variants: a consensus classification system by a multispecialty Fabry disease genotype–phenotype workgroup

BackgroundFabry disease (α-galactosidase deficiency) is an X-linked genetic disease caused by a variety of pathogenic GLA variants. The phenotypic heterogeneity is considerable, with two major forms, classic and later-onset disease, but adjudication of clinical phenotype is currently lacking for many variants. We aimed to determine consensus phenotypic classification for previously unclassified GLA variants from the GLA-specific fabry-database.org database.MethodsA Fabry disease genotype–phenotype workgroup developed a five-stage iterative system based on expert clinical assessment, published literature and clinical evidence of pathogenicity using a 2-point scoring system based on clinical hallmarks of classic disease. Kaplan–Meier (KM) analysis of severe clinical event-free survival was used as final validation. Results were compared with those from web-based disease databases and in silico pathogenicity prediction programmes.ResultsFinal consensus on classifications of ‘pathogenic’ was achieved for 32 of 33 GLA variants (26 ‘classic’ phenotype, 171 males; 6 ‘later-onset’ phenotype, 57 males). One variant remained of uncertain significance. KM curves were similar for the known fabry-database.org database phenotypes and when workgroup consensus classifications were added, and the curves retained the same separation between ‘classic’ and ‘later-onset’ phenotypes.ConclusionThe iterative system implemented by a Fabry disease genotype–phenotype workgroup achieved phenotypic classifications for variants that were previously unclassified. Clinical pathogenicity associated with a particular GLA variant defined in affected males appears to have predictive value and also generally correlates with risk for affected females. The newly established classifications can be of benefit to the clinical care of Fabry patients harbouring these variants.