eprintid: 1573199 rev_number: 36 eprint_status: archive userid: 608 dir: disk0/01/57/31/99 datestamp: 2017-09-12 10:23:13 lastmod: 2021-12-13 02:59:31 status_changed: 2017-09-12 10:23:13 type: article metadata_visibility: show creators_name: Bradford, KL creators_name: Moretti, FA creators_name: Carbonaro-Sarracino, DA creators_name: Gaspar, HB creators_name: Kohn, DB title: Adenosine Deaminase (ADA)-Deficient Severe Combined Immune Deficiency (SCID): Molecular Pathogenesis and Clinical Manifestations ispublished: pub divisions: UCL divisions: B02 divisions: D13 keywords: Adenosine Deaminase, Clinical trials, Gene therapy, Lymphopenia, Purine metabolism, SCID note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. 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. date: 2017-10 date_type: published official_url: http://doi.org/10.1007/s10875-017-0433-3 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1418152 doi: 10.1007/s10875-017-0433-3 pii: 10.1007/s10875-017-0433-3 lyricists_name: Gaspar, Hubert lyricists_id: HBGAS19 actors_name: Waragoda Vitharana, Nimal actors_id: NWARR44 actors_role: owner full_text_status: public publication: Journal of Clinical Immunology volume: 37 number: 7 pagerange: 626-637 event_location: Netherlands issn: 1573-2592 citation: Bradford, KL; Moretti, FA; Carbonaro-Sarracino, DA; Gaspar, HB; Kohn, DB; (2017) Adenosine Deaminase (ADA)-Deficient Severe Combined Immune Deficiency (SCID): Molecular Pathogenesis and Clinical Manifestations. Journal of Clinical Immunology , 37 (7) pp. 626-637. 10.1007/s10875-017-0433-3 <https://doi.org/10.1007/s10875-017-0433-3>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/1573199/1/Gaspar_revision%202%20HBG_KLB.pdf