APDS in a 3-year-old boy presenting with EBV viremia and hodgkin lymphoma associated with a novel germline heterozygous variant in PIK3CD and with characteristic immune phenotype but no upregulation of the T cell mTOR pathway.

BACKGROUND: Activated phosphoinositide 3-kinase δ syndrome (APDS) is an inborn error of immunity in the PIK3CD gene caused by an increase in phosphoinositide 3-kinase δ (PI3Kδ) activity. APDS is characterized by immune dysregulation such as senescent T cells, lymphoproliferation, and hypogammaglobulinemia. Patients present with lymphoid hyperplasia, recurrent sinopulmonary infections, recurrent viremias, and lymphomas.

CASE PRESENTATION: We present a case report of a patient with APDS due to a novel variant in the PIK3CD gene. Our patient was identified at 3 years of age due to persistent EBV viremia and Hodgkin lymphoma. Immune evaluation demonstrated upregulation of T follicular helper cells and CD10 + B cells were consistent with the lymphocytic phenotype present in patients with APDS. However, there was no upregulation of the T cell mTOR pathway by functional testing. The patient was found to carry a novel variant, (c.58G > A p.(Val20lle)), in the PIK3CD gene.

CONCLUSIONS: We describe a 3-year-old patient with a novel variant in the PIK3CD gene (c.58G > A p.(Val20lle)) presenting with EBV viremia, Hodgkin lymphoma, upregulation T follicular helper cells and CD10 + B cells consistent with a phenotype of APDS in a 3-year-old boy. This case broadens our understanding of the genetic and phenotypic spectrum of PIK3CD gene mutations in APDS.