BackgroundActivated phosphoinositide 3-kinase syndrome (APDS) is a rare inborn error of immunity with an autosomal-dominant inheritance pattern that leads to immune dysregulation. Presently, the natural history of disease for persons with APDS is incompletely understood, particularly among pediatric and adolescent individuals.MethodsThe APDS Characterization and Clinical Outcomes Immunologic Registry (APDS-CHOIR) follows participants in the United States with variants in PIK3CD or PIK3R1. The registry captures electronic health record (EHR) data historically and over time, including demographics, comorbidities, incident medical conditions, medications, medical procedures, and transplant history. In this study, we describe the demographic and clinical features of participants younger than 18 years at the time of enrollment over a one-year follow-up period.ResultsParticipants were followed for at least one year (n = 14). Of those, 8 (57%) were female, and 43% were male; most self-identified as white (n = 10; 71%) and had pathogenic PIK3CD variants (n = 10; 71%). Age at diagnosis ranged from 2 to 12 years (median 7, interquartile range IQR 2–9, n = 11), and age at enrollment ranged from 2 to 14 years (median 9.5, IQR 7–14). Most participants had history at the time of enrollment of infections (n = 11; 79%), respiratory issues (n = 11; 79%), lymph node abnormalities (n = 9; 64%), splenomegaly (n = 8; 57%), and gastrointestinal issues (n = 8; 57%); detailed medical history is described in the supplementary table. Two participants had a history of bone marrow transplants, and one participant underwent a bone marrow transplant during follow-up. Two mild infections were reported during follow-up. During the study period, 10 participants (71%) received immunoglobulin replacement therapy. Sirolimus was used by six participants (43%) and leniolisib by one participant (7%). One participant died during follow-up from multisystem complications related to a bone marrow transplant at the age of 14.ConclusionsThis study provides a detailed characterization of pediatric individuals with APDS over one year of follow-up, demonstrating variable clinical manifestations and management approaches. Given the paucity of clinical information regarding APDS in this population, these findings may improve the characterization of disease presentation and progression in children and adolescents.Tabular data are included as downloadable supplement files.
Rider et al. (Fri,) studied this question.