Lymphoproliferation and hyper-IgM as the first manifestation of activated phosphoinositide 3-kinase δ syndrome (APSD 2): case report

Abstract

Activated phosphoinositide 3-kinase δ syndrome (APDS) stands as an inborn error of immunity arising from mutations within the genes responsible for encoding PI3Kδ subunits. This results in an excessive activation of the PI3K signaling pathway. Gain-of-function mutations in PIK3R1 (encoding p85α, p55α, and p50α) lead to the development of APDS2. Notably, the clinical presentations of this syndrome often closely resemble those of other primary immunodeficiencies.
We present a case involving a 15-year-old male who displayed an immunological phenotype that bore a striking resemblance to hyper IgM syndrome. To pinpoint the underlying genetic mutation, comprehensive whole exome sequencing was undertaken.
Our investigation successfully identified a heterozygous splice site mutation, previously reported within the well-established hotspot of the PIK3R1 gene (GRCh37, c.1425+1 G>T). The diverse spectrum of inborn errors of immunity underscores the pivotal role of identifying gene mutations, particularly in patients who present with clinical manifestations spanning autoimmune disorders, lymphoproliferative conditions, and antibody deficiencies. Such precise genetic diagnoses hold significant potential for improving patient care and management.