Clinical and immunological spectrum of five patients with activated phosphoinositide 3-kinase δ syndrome 1: A multicentric study from India

Activated phosphoinositide 3-kinase δ syndrome 1 (APDS1) is a combined immunodeficiency caused by monoallelic gain-of-function mutations in the PIK3CD gene. Patients with APDS1 have significant sinopulmonary involvement, lymphoproliferation, and autoimmune manifestations. We analyzed the clinical profile, treatment, and outcomes of five patients with APDS1. A total of 556 patients were diagnosed with inborn errors of immunity at our center between February 2017 and October 2025. Five patients had APDS1, confirmed by next-generation sequencing. Their records were analyzed in detail. The male-to-female ratio was 4:1. The mean age at symptom onset and at diagnosis was 14.8 and 62 mo, respectively. The age at onset of infections (mean age: 26 mo) preceded lymphoproliferation (mean age: 36 mo). Sinopulmonary infections (n = 3), recurrent gastroenteritis (n = 2), oral candidiasis (n = 1), and meningoencephalitis (n = 1) were the most commonly noted infections. Lymphoproliferation was seen in four patients, the most common being cervical lymph node enlargement (n = 4), followed by adenotonsillar hypertrophy (n = 3) and chronic splenomegaly (n = 3). Three of these patients with lymphoproliferation had Epstein-Barr viremia. Inflammatory colitis (n = 1) was the sole autoimmune manifestation noted in our cohort. Lymphocyte subset analysis showed increased CD8 cells and a reversal of the CD4:CD8 ratio (n = 4). Therapy included antibiotic prophylaxis (n = 5), intravenous immunoglobulin replacement therapy (n = 3), steroids (n = 3), mycophenolate mofetil (n = 1), and sirolimus (n = 1). Presently, four patients are alive and doing well, while one child is lost to follow-up. To the best of our knowledge, this is the first case series of APDS1 from the Indian subcontinent. We observed a significant delay in the diagnosis of these patients highlighting the need for raising awareness regarding this entity among pediatricians and primary care physicians.