Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 21 2 2022 04 11 219 227 Saja Fetyan Division of Pediatrics, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates Nida Sakrani Division of Pediatrics, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates Fawwaz Yassin Division of Pediatrics, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates Mohammad Abdallah Division of Pediatrics, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates Naser Elzein Division of Pediatrics, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates Gholamreza Azizi Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran Gehad ElGhazali Department of Immunology, Sheikh Khalifa Medical City- Union 71/Purehealth, and Faculty of Medicine, United Arab Emirates University, Al Ain, United Arab Emirates 2021 07 21 2021 11 06 LPS-responsive beige-like anchor protein (LRBA) deficiency is a primary immunodeficiency caused by a mutation in the LRBA gene. Affected individuals present with a variety of clinical symptoms including hypogammaglobulinemia, recurrent infections, splenomegaly, hepatomegaly, and autoimmune cytopenias. Except for hypogammaglobulinemia, the remaining features resemble autoimmune lymphoproliferative syndrome (ALPS). Here, we report the case of a 14-year-old boy with the ALPS phenotype, eventually diagnosed with LRBA deficiency. He presented with lymphadenopathy and hepatosplenomegaly, along with autoimmune cytopenia. Due to recurrent infections and worsening gastrointestinal symptoms, whole-exome sequencing was conducted and revealed a novel homozygous pathogenic variant in the LRBA gene (c.534del; p.9Asp179IIef*16). The patient recently suffered from clinical deterioration due to SARS-COV-2 which appears to have triggered an acute worsening of his existing Cytomegalovirus colitis leading to an eventual demise. A literature search for reported LRBA deficient patients with ALPS-like phenotype revealed 11 patients. The most common clinical presentations in LRBA patients with ALPS-like phenotype included autoimmunity (100%), splenomegaly (91%), lymphadenopathy (36.4%), and respiratory tract infections (63.6%). LRBA deficiency is unique in the fact that it encompasses immune deficiency, autoimmunity, and lymphoproliferation. In children with multiple symptoms related to these domains, a genetic diagnosis is necessary to ensure tailored and precise medical therapy. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3296 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3296/1834