APDS [Activated phosphoinositide 3-kinase (PI3K) δ Syndrome] is a recently discovered form of primary immunodeficiency. It is induced by gain-of-function mutations in genes encoding PI3Kδ subunits and over-activation of the PI3K signaling pathway. As of April 2019, the cohort of APDS patients in the European Society for Immunodeficiencies (ESID) registry consists of 87 patients, with updates following. In this study, we report a 5-year-old girl with a mutation in the PIK3CD gene.
Target gene sequencing was performed to detect the genetic mutation in this patient.
5-year-old female patient, full-term, birth weight 3500g, no family history of an immunodeficiency. At 3 months – BCG-itis, received Isoniazid and Rifampicin successfully. Since the age of 7 months has been diagnosed with recurrent cases of pneumonia, bronchitis, sinusitis, spread molluscum contagiosum infection. During examination: malnourished, multiple molluscum contagiosum lesions, lymphadenopathy, splenomegaly (+4 cm). CT demonstrates fibrosis in the left lung (S9-10), lymphadenopathy (chest) and severe splenomegaly. Laboratory data: WBC count 2,9*10 3/uL, platelets 109*10 3/uL, IgG 850 (701-1157 mg/dL), IgA 76 (66-120 mg/dL), IgM 155 (38-74 mg/dL), CD3+ 0,6 (1,8-3,0*10 3/uL), СD19+ 0,06 (0,35-1,43*10 3/uL). Epstein-Barr virus infection was confirmed by peripheral-blood PCR. Bone marrow biopsy: no data for myelodysplastic syndrome. Targeted sequencing: heterozygous splice site autosomal mutation in the hot spot of the PIK3CD c.3061G>A, p.E1021K. The patient received immunoglobulin replacement, Rituximab was prescribed.
Rituximab, Sirolimus, and inhibitors of PI3Kδ could be efficient for the treatment of APDS because the lymphoproliferative syndrome is leading. HSCT may be a curative treatment for these patients.