Diagnostic odyssey of patients with the rare immunodeficiency activated PI3 kinase delta syndrome (APDS): case study from expert and patient surveys

The interviews revealed a median diagnostic delay of several years, mainly due to the rarity and phenotypic heterogeneity of APDS and the involvement of multiple specialties prior to referral to an immunologist. Many patients initially received symptomatic treatment before an underlying immune disorder was suspected. Physicians emphasized the decisive role of genetic testing for confirmation, while patients frequently described the diagnosis as a "lucky coincidence". Both groups highlighted structural barriers including limited awareness, fragmented care, and delayed access to targeted therapy. Early recognition of APDS requires specific education across specialties, wider access to genetic testing, and the development of standardized diagnostic and disease activity tools. Strengthening interdisciplinary care pathways and timely initiation of APDS-specific therapy may substantially improve outcomes in this ultra-rare immunodeficiency.