Transverse myelitis in a patient with activated phosphoinositide 3-kinase δ syndrome type 1

Abstract

Activated phosphoinositide 3-kinase (PI3K)δ syndrome (APDS) is a heterogenous primary immunodeficiency caused by autosomal dominant mutations in PIK3CD (APDS1) or P1K3R1 (APDS2), genes that code for the catalytic p110δ and regulatory p85 subunits of PI3Kδ respectively 1,2 . Both forms of APDS result in overactivation of PI3Kδ through gain-of-function mutations in p110δ or loss-of-function mutations in p85 and present with similar immunodeficiency. Over ninety percent of APDS patients present with recurrent ear, nose and throat or respiratory tract infections 1,2 . Both nonneoplastic and neoplastic lymphoproliferation are common, with lymphoma the most frequently experienced malignancy 1,2 . Almost 40% of patients with APDS1 and 20% of patients with APDS2 experience autoimmune or inflammatory disease such as cytopenias, chronic diarrhoea or autoimmune haemolytic anaemia. The majority of patients with APDS are treated supportively with antibiotic prophylaxis. Other therapeutic options include immunoglobulin replacement therapy (IGRT), immunosuppressive therapies and inhibitors of mTOR signalling such as rapamycin 3 . Rapamycin appears to be more effective at controlling non-neoplastic lymphoproliferation but less successful at modulating intestinal disease and cytopenias 3 .