What genetic deficiency causes severe combined immunodeficiency (SCID)?

Severe combined immunodeficiency (SCID) is a group of disorders characterized by the absence of both T-cell and B-cell immune responses, leading to a high susceptibility to infections. One of the most well-known genetic causes of SCID is adenosine deaminase (ADA) deficiency.

ADA is an essential enzyme in the purine salvage pathway, which is crucial for the breakdown of adenosine and deoxyadenosine. When ADA is deficient, toxic metabolites accumulate, particularly in lymphocytes, leading to their apoptosis or dysfunctional development. This results in the severe lymphopenia (low lymphocyte count) observed in patients with SCID.

Patients with ADA deficiency typically present in infancy with recurrent infections, failure to thrive, and they often lack effective immune responses. Treatment options include enzyme replacement therapy and stem cell transplantation.

Understanding the role of ADA deficiency highlights the importance of metabolic processes in immune function, linking a specific genetic deficiency directly to the immune system's ability to respond to pathogens. This clear mechanism of action helps to identify ADA deficiency as a classic cause of SCID in the context of immunodeficiencies.