Multiple presentations of pediatric activated PI3K-delta syndrome: a single-center experience in south-central mainland China

Abstract

Abstract Background Activated phosphoinositide 3-kinase delta syndrome causes recurrent respiratory tract infections, lymphoproliferation, autoimmunity, and lymphoma, due to mutations in PI3Kδ subunits, encoded by PIK3CD and PIK3R1, or PTEN, resulting in APDS1, APDS2, and APDS-L subtypes, respectively. Over 400 cases of APDS have been recognized since 2013; however, reports of pediatric patients from China are relatively limited.Methods Herein, individuals diagnosed with APDS by whole-exome sequencing from a single center in China were retrospectively assessed. Demographic characteristics, disease complications, laboratory data, and genetics were reviewed based on medical records.Results Ten, two, and nine patients with APDS1, APDS2, and APDS-L, respectively, were included. All patients with APDS1 had the c.3061G > A mutation in PIK3CD; patients with APDS2 had heterozygous c.1425 + 1G > C and c.1425 + 1G > A mutations in PIK3R1; and of patients with APDS-L, four had c.388C > T, and the other five had c.697C > T, c.1031delA, c.202T > C, c.640C > T, and c.896dupA mutations in PTEN. Recurrent respiratory tract infections were the most common manifestations in all patients. Neurodevelopmental abnormalities were noted in all patients with APDS-L. Bronchiectasis, chronic lymphoproliferation, and autoimmunity were more common in patients with APDS1 and APDS2. Five patients with APDS1 died from complications, including severe bacterial infection, autoimmune disease, renal failure, and lymphoma. Decreased serum IgG levels, increased IgM levels, B cell lymphopenia, and CD4 lymphopenia were predominant immunologic features in patients with APDS1 and APDS2.Conclusions APDS is a combined immunodeficiency with variable clinical manifestations. Patients with APDS1 and APDS2 had more frequent and severe infections than those with APDS-L. Neurodevelopmental delay was common in patients with APDS-L. APDS can be fatal; appropriate management is required to improved patient outcomes.