Activated PI3K delta syndrome

Activated PI3K Delta Syndrome

Diagram of autosomal dominant inheritance

Structure of PI3 kinase

Activated PI3K Delta Syndrome (APDS) is a rare primary immunodeficiency disorder characterized by mutations in the PIK3CD gene, which encodes the p110_ catalytic subunit of phosphoinositide 3-kinase (PI3K). This condition leads to immune dysregulation, recurrent infections, and increased susceptibility to lymphoproliferative disorders.

Pathophysiology

APDS is caused by gain-of-function mutations in the PIK3CD gene, resulting in hyperactivation of the PI3K delta pathway. This hyperactivation affects the development and function of B cells, T cells, and natural killer cells, leading to immune system dysfunction. The PI3K delta pathway is crucial for the regulation of immune cell signaling, and its dysregulation can result in impaired immune responses and increased risk of autoimmunity.

Clinical Features

Patients with APDS typically present with recurrent sinopulmonary infections, lymphadenopathy, and hepatosplenomegaly. They may also develop autoimmune disorders and have an increased risk of lymphoma. The condition is often diagnosed in childhood, but symptoms can vary widely among individuals.

Diagnosis

Diagnosis of APDS involves genetic testing to identify mutations in the PIK3CD gene. Immunological assessments may reveal abnormalities in B and T cell populations, as well as impaired antibody responses. Clinical evaluation of recurrent infections and lymphoproliferative symptoms is also essential for diagnosis.

Treatment

Management of APDS includes the use of antibiotics to prevent and treat infections, such as amoxicillin. Immunoglobulin replacement therapy may be necessary for patients with significant antibody deficiencies. Targeted therapies, such as PI3K inhibitors, are being investigated as potential treatments to address the underlying immune dysregulation.

Related Pages

• Primary immunodeficiency
• PIK3CD
• Lymphoproliferative disorder
• Autoimmunity

Gallery

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  Structure of amoxicillin

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  Autosomal dominant inheritance pattern

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  Structure of PI3 kinase

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  Chemical structure of Amoxicillin