Abstract
Activated phosphoinositide 3-kinase δ syndrome (APDS) is an autosomal dominant primary immunodeficiency caused by gain-of-function (GOF) mutations in PIK3CD or PIK3R1 genes. The phenotypes of APDS are highly variable, ranging from asymptomatic adults to profound immunodeficiency causing early death in childhood. Herein, we reported two pediatric patients with APDS presented with recurrent lung infections, sinusitis, hematuria, and positive anti-neutrophil cytoplasmic antibody (ANCA), previously diagnosed as granulomatosis with polyangiitis (GPA). Bronchoscopy showed mucosal nodule lymphoid hyperplasia in the entire airway. Many inflammatory cells infiltrated around the airway and in the lung parenchyma, and numbers of CD3+ T cells and CD20+ B cells were significantly increased, especially CD3+ T cells. Whole exome sequencing showed that they had the E1021K (c.3061 G >A) mutation in the PIK3CD gene. These are the first reported cases of APDS presenting as childhood-onset GPA. Pediatricians should suspect of APDS in the differential diagnosis of children who present with GPA-like symptoms. Additionally, timely and repeated bronchoscopies could contribute to providing an important diagnostic clue for APDS.
Highlights
Activated phosphoinositide 3-kinase (PI3K) d syndrome (APDS) is an autosomal dominant primary immunodeficiency
Primary sclerosing cholangitis (PSC) not associated with Cryptosporidium parvum infection was described in the adults [6]
We described two pediatric patients with APDS1 who presented with granulomatosis with polyangiitis (GPA) including recurrent lung infections, sinusitis, hematuria, and positive anti-neutrophil cytoplasmic antibody (ANCA)
Summary
Activated phosphoinositide 3-kinase (PI3K) d syndrome (APDS) is an autosomal dominant primary immunodeficiency It is caused by gain-of-function (GOF) mutations in PI3Kd catalytic subunit p110d (encoded by the PIK3CD gene) or regulatory subunit p85a (encoded by the PIK3R1 gene) leading to APDS1 and APDS2, respectively [1, 2]. A study by Crank et al showed that patients with PIK3CD mutations presented with a classic hyper IgM phenotype during childhood and as young adults developed non-EBV-associated hematologic malignancies [5]. Patients with APDS may exhibit increased polymerized actin and increased apoptosis, likely leading to widespread necrotic skin lesions [7] Both mutations that reduce PI3Kd activity and GOF mutations in PI3Kd will cause defective lymphocyte development and function. We report two pediatric patients with APDS presented with recurrent lung infections, sinusitis, hematuria, and positive anti-neutrophil cytoplasmic antibody (ANCA), previously diagnosed as GPA.
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