Autoimmune lymphoproliferative syndrome (all types) generally presents in early childhood, and is characterized by chronic, non-malignant lymphadenopathy, usually with autoimmunity. The underlying cause is a defect in lymphocyte apoptosis, or programmed cell death, leading to persistence of mature T and B cells, including the usually rare CD4/CD8-double-negative T (DNT) cell. The formal diagnostic triad for ALPS is elevated DNT cells, hepato/splenomegaly, and defective in vitro lymphocyte apoptosis. Autoimmunity may be present, most often directed against erythrocytes, platelets and neutrophils. In some patients, skin rashes, glomerulonephritis, arthritis, Guillan-Barré syndrome and autoimmune hepatitis may occur. The disorder can vary significantly in severity, even within families. Some individuals have only positive laboratory findings, typically including DNT cells, autoantibodies (such as Coombs positivity), hypergammaglobulinemia (IgG, IgM, IgA), elevated serum IL-10, and elevated serum vitamin B12. The majority of ALPS patients have mutations in the FAS (TNFRSF6) gene and are referred to as Type IA. ALPS cases associated with CASP8 and CASP10 mutations are extremely rare and less well understood. ALPS2B has been called Caspase-8 Deficiency State (CEDS) because the two published siblings have immunodeficiency in addition to ALPS.