PIK3CD VUS in a patient with common variable immunodeficiency

SEMINARIO, A. G.; GAILLARD, MARÍA ISABEL; REGAIRAZ, LORENA; BEZRODNIK, LILIANA; MOREIRA, I.; CALDIROLA, MARÍA SOLEDAD

Simposio; 2020 CIS Annual meeting; 2020

63 year old woman with personal history of severe and recurrent upper and lower respiratory infections, chronic pulmonary disease with bilateral bronchiectasis and several micro nodules, chronic diarrhea without diagnosis (colonoscopy with mild colitis, without CMV. No bacterias no parasits were found in stools), mild osteopenia, focal lesion in right hepatic lobe, atopic dermatitis and anemia. She was followed up in other center and in 1996 she was diagnosed with c ommon variable immunodeficiency (CVID) and started treatment with intravenous immunoglobulin (IVIG), butwith lowadherence to it. She did not have referred history of lymphoproliferation nor significant viral infections. She had a daughter with spherocytosis who required esplenectomy and also had bronchiectasis and CVID diagnosis, she deceased at 28 years old due to pulmonary infection. One 30 years old son has anemia. Her other daughter and son are healthy. In our f i r s t immunologic assessment we found severe hypogammaglobulinemia with absence of B cells in peripheral blood.She started with high doses of IVIG (800 mg/k/month) and antibiotic prophilaxis with of the functional respiratory test and without new infections.Thinking that her clinical picture could be other than CVID we order a genetic study. A Nextera Exome Capture and Next Generation Sequence with Illumina HiSEq was made and an heterozygous VUS in PIK3CD gene (chr1:9. 775. 746, p. P97A) was found. Her son with anemia also have the same variant. (His immunological studiesoill pending). Now a days she is stable, without infections with IVIG and antibiotic prfilaxis but because of the chronic diarrhea and the pulmonary compromise, she began with sirolimus but it was suspended because severe intolerance (vomiting and diarrhea that caused dehydration). In plan toiniciate treatment with mycophenolate mofetil. Conclusion: Clinical presentations of primary immunodeficiencies are becoming more complex, and their diagnosis imply a challenge for immunologist nowadays. Studies with Next Generation Sequence is a very useful tool in undefined cases, especially when more than one member in the family are involved.