PI3Kδ is a heterodimeric complex containing a p110δ catalytic molecule and a p85a regulatory subunit encoded by the PIK3CD and PIK3R1 genes, which play a critical role in the regulation of immune responses.The heterozygous gain of function mutations of p110δ, and exon-skipping mutations of p85a cause hyperactivation of the PI3Kδ complex and cause APDS type 1 (APDS1) and APDS2. Patients present in the childhood with recurrent bacterial and viral sinopulmonary infections which often complicate with bronchiectasis. Autoimmune cytopenia and gastrointestinal findings are also frequently observed. There is increased risk of lymphoproliferative diseases, and lymphoma.
Here, we present a case with PIK3R1 defect diagnosed with CVID.
At 5 years of age, the patient was admitted to the hospital due to recurrent lung infections, pleural effusion, and the history of zona zoster infection. Intravenous immunoglobulin(IVIG)treatment was started with the diagnosis of CVID at 7 years of age because of hypogammaglobulinemia and absence of specific antibody response, . In addition to low immunoglobulin levels, B cell (CD19+) percentage and counts progressively decreased during follow-up. Thorax CT revealed millimetric nodular opacities in both lungs and mucus plugs.
At the age of 20, the molecular analysis revealed mutation in PIK3R1 gene (c.712C> T, p. Leu238Phe).
APDS should be kept in mind in patients presenting with recurrent lung infections and inflammatory diseases.Molecular diagnosis provides clinicians to use mTOR or PI3Kδ inhibitors in the management of patients as a bridge therapy until HSCT is performed.