LPS-responsive beige-like anchor protein deficiency

Autosomal recessive - en

LPS-responsive beige-like anchor (LRBA) protein deficiency is a rare immunodeficiency disorder characterized by a mutation in the LRBA gene. This condition affects the immune system, leading to a wide range of clinical manifestations including autoimmunity, recurrent infections, and enteropathy. LRBA protein plays a crucial role in the regulation of immune cell function, particularly in the maintenance and survival of regulatory T cells (Tregs) and the trafficking of intracellular vesicles.

Etiology

LRBA deficiency is caused by autosomal recessive mutations in the LRBA gene located on chromosome 4q31. This gene encodes the LRBA protein, which is involved in the intracellular trafficking processes that are essential for the normal function of the immune system. The mutations lead to either a significant reduction or a complete loss of LRBA protein function.

Clinical Manifestations

Patients with LRBA deficiency present a broad spectrum of clinical features, which can vary significantly among affected individuals. Common symptoms include:

• Autoimmune diseases such as autoimmune hemolytic anemia, autoimmune thrombocytopenia, and autoimmune enteropathy.
• Recurrent infections due to the impaired immune response.
• Enteropathy characterized by diarrhea, which can lead to failure to thrive in children.
• Endocrinopathy, often presenting as hypothyroidism.
• Lung disease, including interstitial lung disease and bronchiectasis.

Diagnosis

The diagnosis of LRBA deficiency is based on clinical presentation, laboratory findings, and genetic testing. Laboratory tests may reveal abnormalities such as low immunoglobulin levels, elevated autoantibodies, and reduced numbers of regulatory T cells. Confirmatory diagnosis is achieved through genetic testing, which identifies mutations in the LRBA gene.

Treatment

Treatment of LRBA deficiency is tailored to the individual's symptoms and may include:

• Immunoglobulin therapy to prevent infections.
• Immunosuppressive therapy to control autoimmune manifestations. Medications such as rituximab, sirolimus, or abatacept may be used.
• Hematopoietic stem cell transplantation (HSCT) has been successful in some cases, offering the potential for a cure by reconstituting a functional immune system.

Prognosis

The prognosis for individuals with LRBA deficiency varies depending on the severity of symptoms and the effectiveness of treatment. Early diagnosis and appropriate management are crucial for improving outcomes. However, the condition can be life-threatening, particularly in cases with severe autoimmune complications or infections.

See Also

• Primary immunodeficiency
• Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)
• Common variable immunodeficiency (CVID)