Case Report: First occurrence of smoldering multiple myeloma in activated phosphoinositide 3-Kinase δ syndrome

Activated phosphoinositide 3-kinase δ syndrome (APDS) is a newly described inborn error of immunity. Heterozygous mutations in the PI3Kδ catalytic subunit p110δ (PIK3CD) or regulatory subunit p85α (PIK3R1) lead to APDS1 and APDS2, respectively. Clinical manifestations include lymphoproliferation, recurrent respiratory tract infections, herpesvirus infections, enteropathy, elevated IgM, autoimmunity, and increased susceptibility to tumors, particularly lymphoma. Smoldering multiple myeloma (SMM), an asymptomatic clonal plasma cell disorder considered a pre-malignant entity, may progress to symptomatic multiple myeloma (MM) over time. This report describes a young patient with recurrent respiratory tract infections (pneumonia, bronchiectasis, and otitis media), lymphoproliferation, genital herpes, autoimmunity, and elevated serum IgM and IgG levels. Whole-exome sequencing identified a heterozygous PIK3CD gene mutation (c.1002C>G, p.Asn334Lys), and Sanger sequencing confirmed the same mutation in the patient's son. Bone marrow aspiration and serum immunofixation electrophoresis confirmed monoclonal plasma cell proliferation, supporting a diagnosis of SMM. The patient did not receive targeted therapy. Early genetic sequencing can facilitate timely diagnosis of APDS and improve prognosis. To the best of our knowledge, this is the first reported case of APDS coexisting with SMM.