Severe combined immunodeficiency—a purine metabolism disorder
Severe combined immunodeficiency (SCID) is a primary immune deficiency that is a pediatric emergency. Left untreated, patients will die prior to 2 years of age from overwhelming infection. There are many known causes of SCID, but this review focuses on adenosine deaminase (ADA) deficiency. 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. 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. 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. 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.