combined immunodeficiency due to LRBA deficiency

Combined immunodeficiency due to LRBA deficiency is an inherited condition that affects the immune system, leading to both recurrent infections and autoimmune problems. It results from pathogenic changes in the LRBA gene, which plays an important role in regulating immune cell function. This condition is very rare, affecting fewer than 1 in one million people, and typically presents in early childhood. Although the clinical features can be diverse, its recognition relies on a pattern of recurrent infections and laboratory evidence of immune dysregulation.

Individuals with combined immunodeficiency due to LRBA deficiency experience a range of clinical features that reflect immune system dysfunction. Common and characteristic findings include recurrent respiratory infections, pneumonia, and sepsis, as well as persistently decreased neutrophil counts and diminished class-switched memory B cell proportions. Additional features reported in many affected individuals include generalized lymphadenopathy, splenomegaly, and various autoimmune manifestations such as autoimmune thrombocytopenia, autoimmune hemolytic anemia, and type I diabetes mellitus. Gastrointestinal issues like chronic diarrhea and villous atrophy, along with dermatologic findings such as erythema nodosum and vitiligo, are also observed. Not all individuals experience all features, and severity varies considerably.

This condition is caused by pathogenic variants in the LRBA gene, which encodes a protein important for regulating immune response. Disruption of LRBA function impairs normal immune regulation, making affected individuals susceptible to both recurrent infections and autoimmune problems. It is inherited in an autosomal recessive pattern, meaning that a person must inherit two defective copies of the gene to develop the condition. Because this condition is more common when parents share a common ancestor, carrier testing and genetic counseling may be particularly relevant for families with a history of related ancestry.

Currently, management focuses on supportive care and symptom management since there are no approved or foundational therapies specifically linked to LRBA deficiency. Treatment is tailored to the individual's unique clinical picture and is typically provided by a multidisciplinary team. In practice, this may include acute interventions for infections or autoimmune episodes along with ongoing surveillance to detect potential complications early. Genetic counseling is recommended for families, and patients should discuss treatment options with their healthcare team to determine the most appropriate management strategy.

The clinical course of combined immunodeficiency due to LRBA deficiency can vary widely, with outcomes depending on the severity of recurrent infections and autoimmune complications. With current standards of care and a multidisciplinary approach, many individuals experience improved quality of life and stabilization of symptoms over time. Outcomes have improved as supportive care strategies and regular surveillance help manage complications before they become severe. It is important for families to connect with specialists such as immunologists and genetic counselors, as future advances in treatment may further influence the long-term outlook. Outcomes described in medical literature continue to evolve as standards of care improve.