Severe Combined Immunodeficiency (SCID)

Etiology
  • Overview
    • Severe Combined Immunodeficiency (SCID) is the result of combined defects in both B-cells and T-cells, resulting in severely impaired Humoral Immunity and Cell-mediated Immunity. A variety of heritable genetic lesions can cause SCID and thus the disease is in reality a mixture of different genetic etiologies which manifest with similar clinical picture. The two most common causative genetic lesions affect Adenosine Deaminase (ADA) and Cytokine Receptor Gamma Chain.
  • Adenosine Deaminase Deficiency
    • Adenosine Deaminase is a critical enzyme required for nucleotide metabolism, specifically for purine bases. It is thought that build up purines such as adenosine and its metabolites are specifically toxic to lymphocytes and lead to their death.
  • Cytokine Receptor Gamma Chain
    • A variety of cytokine receptors, such as IL-22/4/7/9/11/15, are composed of a common Gamma Chain in the absence of which critical receptor signaling cannot occur. Defects in this common gamma chain appears to completely disrupt proper lymphocyte development.
Clinical Consequences
  • Severe defects in both Humoral Immunity and Cell-mediated Immunity leads to a wide-ranging infection susceptibility to bacteria, viruses, and fungi. Infants born with SCID display failure to thrive and without proper treatment this condition is uniformly fatal early in life. Lymphoid tissue such as the thymus and lymph nodes are hypoplastic and numbers of circulating B-cells and T-cells are severely depressed.
Treatment
  • Bone Marrow Transplantation is the standard treatment. SCID is also of historical interest in terms of advances in clinical application of biomedical research as it was the first human disease to be treated with gene therapy.
Genetics
  • The heritable pattern of SCID varies with the particular gene defect. SCID due to ADA deficiency is inherited in an autosomal recessive fashion. SCID due to Cytokine Gamma Chain Deficiency is inherited in a X-linked recessive.