ADA and severe combined immunodeficiency: Excess intracellular dAdo and dATP cause generalized lymphocyte apoptosis (---> T-B-NK- SCID), while excess extracellular Ado (normally produced by CD4+ TReg lymphocytes) acts on specific receptors with further lymphocyte inhibition [79] and might be important for frequent manifestations of immune dysregulation and autoimmunity (type I diabetes, hypothyroidism, autoimmune thrombocytopenia, hemolytic anemia) also reported in ADA-SCID patients treated by HSCT or gene therapy [80].