Activated phosphoinositide 3-kinase delta syndrome (APDS) is a recently described combined primary immunodeficiency caused by mutations that increase the activity of the phosphoinositide-3-kinase δ (PI3Kδ) pathway. APDS is characterized by the early onset of upper respiratory tract infections, benign chronic lymphoproliferative disorders and other signs of immune dysregulation including gastrointestinal manifestations, autoimmunity and increased risk of malignancy.
Here we describe a 12-year-old girl with a history of chronic diarrhoea, three hospitalizations for sepsis and recurrent respiratory infections. She also presented episcleritis at 4 years of age and exuberant periungual and perioral warts at the age of 5. Her physical examination was relevant for short stature, low weight for age and scoliosis. Immunophenotyping revealed reduced IgG and IgA, but no response to immunization was reported. The cellular immunity studies showed an important reduction of T CD4+ lymphocytes, CD4+/CD8+ ratio inversion, reduction of recent thymic emigrants and increased activated TCD4+ and CD8+. Moreover, reduced switched memory B cells were reported as well as low NKs levels. She carried a heterozygous mutation of the PIK3R1 gene (c.1305A>C) not previously described in the literature. The initial management included vaccine boosters, anti-microbial prophylaxis and immunoglobulin replacement, resulting in significant improvement in weight gain and growth and a reduction in the incidence of respiratory tract infections.
The growing number of patients with APDS since the condition was first described in 2013 indicates that it should be considered in the diagnosis of patients with immunodeficiency, lymphoproliferation, autoimmunity and developmental delay.
Key words: APDS, PIK3R1 gene, primary immunodeficiency, recurrent respiratory tract infection
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