TY - JOUR SP - 626 VL - 37 N1 - This version is the author accepted manuscript. For information on re-use, please refer to the publisher?s terms and conditions. IS - 7 SN - 1573-2592 UR - http://doi.org/10.1007/s10875-017-0433-3 A1 - Bradford, KL A1 - Moretti, FA A1 - Carbonaro-Sarracino, DA A1 - Gaspar, HB A1 - Kohn, DB JF - Journal of Clinical Immunology EP - 637 AV - public Y1 - 2017/10// TI - Adenosine Deaminase (ADA)-Deficient Severe Combined Immune Deficiency (SCID): Molecular Pathogenesis and Clinical Manifestations ID - discovery1573199 N2 - Deficiency of adenosine deaminase (ADA, EC3.5.4.4), a housekeeping enzyme of purine metabolism encoded by the Ada gene, is a cause of human severe combined immune deficiency (SCID). Numerous deleterious mutations occurring in the ADA gene have been found in patients with profound lymphopenia (T(-) B(-) NK(-)), thus underscoring the importance of functional purine metabolism for the development of the immune defense. While untreated ADA SCID is a fatal disorder, there are multiple life-saving therapeutic modalities to restore ADA activity and reconstitute protective immunity, including enzyme replacement therapy (ERT), allogeneic hematopoietic stem cell transplantation (HSCT) and gene therapy (GT) with autologous gene-corrected hematopoietic stem cells (HSC). We review the pathogenic mechanisms and clinical manifestations of ADA SCID. KW - Adenosine Deaminase KW - Clinical trials KW - Gene therapy KW - Lymphopenia KW - Purine metabolism KW - SCID ER -