PASLI disease

Proposed model for the effects of activating substitutions in p110δ

PASLI disease (also known as Activated PI3K-δ Syndrome) is a rare primary immunodeficiency disorder characterized by mutations in the PIK3CD or PIK3R1 genes. These mutations lead to hyperactivation of the PI3K pathway, resulting in immune dysregulation.

Presentation

Patients with PASLI disease typically present with recurrent sinopulmonary infections, lymphadenopathy, and hepatosplenomegaly. Other common features include autoimmunity, enteropathy, and an increased risk of lymphoma.

Genetics

PASLI disease is caused by mutations in the PIK3CD gene, which encodes the p110δ catalytic subunit of phosphoinositide 3-kinase, or the PIK3R1 gene, which encodes the p85α regulatory subunit. These mutations result in the constitutive activation of the PI3K pathway, leading to immune cell dysfunction.

Diagnosis

Diagnosis of PASLI disease involves genetic testing to identify mutations in the PIK3CD or PIK3R1 genes. Additional diagnostic criteria include clinical features such as recurrent infections, lymphoproliferation, and autoimmunity.

Treatment

Treatment for PASLI disease is primarily supportive and includes the use of immunoglobulin replacement therapy, antibiotic prophylaxis, and management of autoimmune complications. Targeted therapies, such as PI3K inhibitors, are being investigated as potential treatments.

Prognosis

The prognosis for individuals with PASLI disease varies depending on the severity of the symptoms and the response to treatment. Early diagnosis and appropriate management are crucial for improving outcomes.

Related Pages

• Primary immunodeficiency
• PIK3CD
• PIK3R1
• PI3K pathway
• Autoimmunity
• Lymphoma