@article{discovery1573199, journal = {Journal of Clinical Immunology}, year = {2017}, title = {Adenosine Deaminase (ADA)-Deficient Severe Combined Immune Deficiency (SCID): Molecular Pathogenesis and Clinical Manifestations}, month = {October}, number = {7}, pages = {626--637}, note = {This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.}, volume = {37}, author = {Bradford, KL and Moretti, FA and Carbonaro-Sarracino, DA and Gaspar, HB and Kohn, DB}, issn = {1573-2592}, abstract = {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.}, url = {http://doi.org/10.1007/s10875-017-0433-3}, keywords = {Adenosine Deaminase, Clinical trials, Gene therapy, Lymphopenia, Purine metabolism, SCID} }