Patients with ALPS have a defect in this apoptotic pathway, leading to chronic non-malignant lymphoproliferation, autoimmune disease, and secondary cancers.

Other manifestations can affect the skin (hives), lungs (bronchiolitis obliterans), or kidneys (autoimmune glomerulonephritis and nephrotic syndrome).

[7] In 2024, a study highlighted the significance of novel genetic markers in the diagnosis and management of ALPS, emphasizing the role of next-generation sequencing in identifying mutations in genes beyond FAS, such as CASP10 and FASLG.

[8] The old diagnostic criteria for the illness included:[13] Chronic non-malignant lymphoproliferation, elevated peripheral blood DNTs and defective in vitro Fas mediated apoptosis.

[citation needed] A definitive diagnosis is chronic non-malignant lymphoproliferation and/or elevated peripheral blood DNTs plus one primary accessory criterion.

First line therapies include corticosteroids (very active but toxic with chronic use), and IVIgG, which are not as effective as in other immune cytopenia syndromes.

[citation needed] Sirolimus (rapamycin, rapamune) which is a mTOR (mammalian target of rapamycin) inhibitor[18] can be active in most patients and can in some cases lead to complete or near-complete resolution of autoimmune disease (>90%)[19][20] With this treatment most patients have complete resolution of lymphoproliferation, including lymphadenopathy and splenomegaly (>90%) and have elimination of peripheral blood DNTs.

Hypothetically, Sirolimus may have lower risk of secondary cancers as opposed to other immune suppressants and requires therapeutic drug monitoring.

It is mostly well tolerated (though side effects include mucositis, diarrhea, hyperlipidemia, delayed wound healing) with drug-drug interactions.