Two cases of successful sirolimus treatment for patients with activated phosphoinositide 3-kinase δ syndrome 1

Abstract

Abstract Background Activated phosphoinositide3-kinase (PI3K) δ syndrome 1 (APDS1) is a novel inborn errors of immunity (IEIs) caused by heterozygous gain of function mutations in PI3Kδ catalytic p110δ (PIK3CD). APDS1 has a spectrum of clinical manifestations. Recurrent respiratory infections, lymphoproliferation, hepatosplenomegaly, hyper-IgM syndrome and autoimmunity are the common symptoms of this disease. Case Presentation Patient 1 presented with recurrent respiratory infections, hepatosplenomegaly and hyper-IgM syndrome. Patient 2 developed early onset systemic lupus erythematosus (SLE)-like disease with resistant thrombocytopenia. c.3061 G > A and c.2314G > A variants in the PIK3CD gene were detected by whole exome sequencing in two patients respectively. c.2314G > A variant in PIK3CD gene of patient 2 is a newly report. After genetic diagnosis, two patients received sirolimus treatment and sirolimus alleviated clinical manifestations, including hepatosplenomegaly in patient 1 and thrombocytopenia in patient 2. Conclusion Genetics diagnosis should be considered in patients with complicated clinical manifestations with no or insufficient response to the conventional therapies. If whole exome sequencing suggests a variant in PIK3CD gene, sirolimus may relieve hepatosplenomegaly and resistant thrombocytopenia. This is the first report of c.2314G > A variant in PIK3CD gene.