Adenosine deaminase severe combined immune deficiency (ADA-SCID) is an ultra-rare, inherited metabolic disorder. ADA-SCID is estimated to occur in approximately 1 in 200,000 to 1 in 1,000,000 newborns around the world.5 The disorder is responsible for approximately 15% of SCID cases.2 Without early diagnosis and effective treatment to restore the immune function children with typical ADA-SCID rarely survive beyond two years of age.2,3
Adenosine deaminase (ADA) enzyme is ubiquitously expressed, with highest levels observed in lymphoid tissues, particularly the thymus, the brain and gastrointestinal tract, and is expressed both intracellularly and on the cell surface. Mutations in the ADA gene leads to the absence or deficiency of ADA enzyme, causing the accumulation of the toxic metabolites adenosine(Ado), 2’deoxyadenosine (dAdo) and deoxyadenosine triphosphate (dATP) and inactivating of S-adenosylhomocysteine hydrolase (SAHase) in cells. ADA-SCID is characterized by severe lymphocytopaenia affecting T-and B-lymphocytes and NK cells, and has been recognized as a systemic metabolic disorder that affects multiple organ systems including the myeloid cells, lungs, brain, skeleton, liver and kidneys, as well as increased risk for development of tumors.
SCID usually can be diagnosed within the first few months of life.2 In some countries, newborn screening for SCID allows for timely detection of ADA-SCID in newborns and initiation of early treatment.
- Whitmore KV, Gaspar HB. Adenosine deaminase deficiency – more than just an immunodeficiency. Front Immunol. 2016; 7:314. doi: 10.3389/fimmu.2016.00314.
- Hershfield M. Adenosine deaminase deficiency. Gene Reviews [Internet]. Initially posted October 2006; updated March 2017. Available at https://www.ncbi.nlm. nih.gov/books/NBK1483/. Accessed December 28, 2017.
- Booth C, Gaspar HB. Pegademase bovine (PEG-ADA) for the treatment of infants and children with severe combined immunodeficiency (SCID). Biologics Targets Ther. 2009;3:349-358.
- Gennery AR, Slatter MA, Grandin L, et al. Transplantation of hematopoietic stem cells and long-term survival for primary immunodeficiencies in Europe: Entering a new century, do we do better? J Allergy Clin Immunol. 2010; 126(3):603-610.
- Gaspar HB, Aiuti A, Porta F, Candotti F, Hershfield MS, Notarangelo LD. How I treat ADA deficiency. Blood. 2009;114:3524- 3532.