ADA deficiency was the first molecular defect to be identified as a cause for immunodeficiency, identified by Dr. This review will focus on SCID caused by adenosine deaminase (ADA) deficiency. Children with SCID whose immune systems are not reconstituted through hematopoietic stem cell transplantation (HSCT), gene therapy, or enzyme replacement (depending on genotype) die in infancy due to opportunistic and severe infections ( 2- 6). Even now there is still a significant minority of cases in which an underlying genetic mutation is not identified ( 1). This wide variety of genotypes under a common phenotypic umbrella is due to the complex interplay of steps that must occur for normal differentiation and maturation of lymphocytes. Severe combined immunodeficiency (SCID) is a collection of at least 17 disorders characterized by defects of T cell number and/or function leading to severe impairment of the cellular and humoral immune response (see Table 1). Received: 09 November 2018 Accepted: 27 November 2018 Published: 28 November 2018. Keywords: Severe combined immunodeficiency (SCID) adenosine deaminase deficiency gene therapy pegademase bovine hematopoietic stem cell transplantation (HSCT) ADA-deficient SCID can be treated through enzyme replacement therapy (ERT), hematopoietic stem cell transplantation (HSCT), or gene therapy, and advances continue to be made every day that improve cost-effectiveness and efficacy of these therapies and make them more widely available to patients.Ĭonclusions: This once-deadly disease is treatable and becoming more easily curable with the technological and scientific advances that allow for permanent immune reconstitution to become accessible to larger numbers of patients. To date, TREC screening has shown 100% sensitivity for SCID but also has brought to light other causes of T cell lymphopenia that were previously lesser known. While previously diagnosed based on recurrent, severe, or unusual infection, SCID is now being diagnosed during its initial asymptomatic period thanks to recent implementation of T cell receptor excision circle (TREC) newborn screening, thus greatly improving survival of patients as treatment can occur before the onset of infection. Key Content and Findings: ADA is a ubiquitous “housekeeping” enzyme, and its deficiency leads to buildup of toxic metabolites, which preferentially affects lymphocytes but also causes non-immune manifestations of disease. Methods: An electronic search was performed on PubMed for relevant articles covering ADA deficient SCID including historical perspective, diagnosis, and treatment. There are many known causes of SCID, but this review focuses on adenosine deaminase (ADA) deficiency. Left untreated, patients will die prior to 2 years of age from overwhelming infection. Background and Objectives: Severe combined immunodeficiency (SCID) is a primary immune deficiency that is a pediatric emergency.