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Activated PI3Kδ syndrome (APDS) is a rare type of inborn error of immunity (IEI), which is characterised by both immune deficiency and immune dysregulation.1-3
First described in 2013, APDS was previously known as PASLI* disease and is one of a group of diseases sometimes known as primary immunodeficiencies (PIDs).1-6
Clinical manifestations of APDS typically begin in childhood and get progressively worse over time, often leading to irreversible organ damage, lymphoma and early mortality.2-4,7
Research suggests that approximately one in four people with APDS face early mortality by the age of 30 years old.8
40%
In almost 40% of cases, patients have a family history of IEIs,9 however APDS can present spontaneously with neither parent being a carrier of the genetic variants which cause the disease.10 It is estimated that APDS affects one to two people per million, including both adults and children.11
APDS is caused by variants in either one of two genes encoding phosphoinositide 3-kinase delta (PI3Kδ), which are vital for the development and function of immune cells.1
The disturbance of homeostatic PI3K signalling leads to abnormalities in immune cell development, cellular metabolism, maturation and proliferation, resulting in both immune deficiency and immune dysregulation.13
Over time, immune deficiency leads to frequent or chronic respiratory / sinopulmonary infections, which can lead to bronchiectasis. It also predisposes to herpes virus infections such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV).3,6
Prolonged immune dysregulation can lead to lymphoproliferation, including lymphadenopathy and splenomegaly, enteropathy, autoimmune disorders and lymphoma.3,6
Patients with APDS typically experience a variety of acute and chronic clinical features within multiple organ systems.3,9,10,14 However, not all patients with APDS experience the same clinical profile, even those within the same family.11
The broad spectrum of clinical manifestations of APDS affecting multiple organ systems over a prolonged period can result in a delayed diagnosis.9
In order to prevent long term complications and early mortality resulting from APDS, timely and accurate diagnosis is key.7
The only definitive way to diagnose APDS is via a genetic test.15
7YRS TO DIAGNOSIS
On average, it takes seven years for a patient to be diagnosed with APDS.9
*P110d-Activating mutation causing Senescent T cells, Lymphadenopathy and Immunodeficiency.