[The autoimmune lymphoproliferative syndrome: a disorder of programmed cell death]

The autoimmune lymphoproliferative syndrome (ALPS) is a chronic, nonmalignant lymphoproliferative disorder caused by mutations in the genes that are involved in programmed cell death (apoptosis). The impaired apoptosis causes accumulation of lymphocytes, which underlies the clinical manifestations of lymphadenopathy, autoimmune phenomena and a markedly increased risk of malignant lymphomas. During the last few decades, great progress has been achieved in elucidating the aetiology of this syndrome. Several mutations have been found in the genes encoding proteins that are involved in the apoptotic cascade, which starts with the binding of the Fas ligand to the transmembranous Fas protein and which is followed by intracellular processes. ALPS is an autosomal dominant hereditary disease with variable penetrance. Unravelling the genetic abnormalities that cause ALPS has provided key insights into the clinical consequences of defective apoptosis.