Review Question - QID 100426

Severe Combined Immunodeficiency (SCID) can be caused by various genetic defects; however, the most common autosomal recessive cause is a deficiency in adenosine deaminase (ADA).

Most cases of SCID are due to defective cytokine receptors resulting from an X-linked mutation of the common gamma-chain of the receptors. Another deficiency responsible for SCID is a deficiency in ADA, which is inherited in an autosomal recessive pattern. Cells lacking this enzyme generate high levels of deoxyadenosine, which is toxic to developing lymphocytes. Bone marrow transplantation and gene therapy are possible treatments.

Aiuti et al. give a review of the recent progress of ADA gene therapy. The authors note that ADA gene transfer is safe and can be very effective in patients suffering from SCID.

Cooper et al. describe SCID as a disease leading to a major reduction in function of T and B-cells. They note that patients with this disorder have an increased risk of recurrent infections and commonly fail to thrive during infancy.

Illustration A depicts the process of gene therapy for patients suffering from SCID. Illustration B displays the major primary immunodeficiencies and what cells they affect.

Incorrect Answers:
Answer 1: In DiGeorge Syndrome, because the 3rd pharyngeal pouch does not develop, the thymus does not develop.
Answer 3: Most Hyper-IgM syndrome patients have an X-linked mutation of the CD40L gene.

Answer 4: In Wiskott-Aldrich Syndrome, there is an X-linked mutation in the WASP gene, leading to recurrent infection amongst other defects.

Answer 5: In Bruton's Agammaglobulinemia, there is an X-linked mutation of a tyrosine kinase called Bruton tyrosine kinase.

Bullet Summary: ADA deficiency is the most common autosomal recessive cause of SCID.