Adenosine Deaminase (ADA)-Deficient Severe Combined Immune Deficiency (SCID): Molecular Pathogenesis and Clinical Manifestations

Kathryn L Bradford; Federico A Moretti; Denise A Carbonaro-Sarracino; Hubert B Gaspar; Donald B Kohn

doi:10.1007/s10875-017-0433-3

Adenosine Deaminase (ADA)-Deficient Severe Combined Immune Deficiency (SCID): Molecular Pathogenesis and Clinical Manifestations

J Clin Immunol. 2017 Oct;37(7):626-637. doi: 10.1007/s10875-017-0433-3. Epub 2017 Aug 25.

Authors

Kathryn L Bradford¹, Federico A Moretti², Denise A Carbonaro-Sarracino³, Hubert B Gaspar², Donald B Kohn^{4

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Affiliations

¹ Department of Pediatrics, University of California, Los Angeles (UCLA), 3163 Terasaki Life Science Bldg., 610 Charles E. Young Drive East, Los Angeles, CA, 90095, USA.
² Centre for Immunodeficiency, Molecular Immunology Unit, University College London Institute of Child Health, London, UK.
³ Department of Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, CA, USA.
⁴ Department of Pediatrics, University of California, Los Angeles (UCLA), 3163 Terasaki Life Science Bldg., 610 Charles E. Young Drive East, Los Angeles, CA, 90095, USA. Dkohn1@mednet.ucla.edu.
⁵ Department of Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, CA, USA. Dkohn1@mednet.ucla.edu.
⁶ Department of Molecular & Medical Pharmacology, UCLA University of California, Los Angeles, CA, USA. Dkohn1@mednet.ucla.edu.

PMID: 28842866
DOI: 10.1007/s10875-017-0433-3

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.

Keywords: Adenosine Deaminase; Clinical trials; Gene therapy; Lymphopenia; Purine metabolism; SCID.

Publication types

Review

MeSH terms

Adenosine Deaminase / deficiency*
Adenosine Deaminase / genetics*
Animals
Disease Models, Animal
Humans
Severe Combined Immunodeficiency / genetics*

Substances

Adenosine Deaminase

Abstract

Publication types

MeSH terms

Substances

Grants and funding