lipopolysaccharide responsive beige-like anchor protein deficiency in a patient with autoimmune lymphoproliferative syndrome-like disease phenotype: a case report and literature review

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.