Severe Combined Immune Deficiency Syndrome - Definition and Overview

Severe Combined Immunodeficiency, or SCID, is a genetic disorder in which both "arms" (B cells and T cells) of the adaptive immune system are crippled. SCID is a severe form of heritable immunodeficiency. It is also known as the "bubble boy" disease because its victims are extremely vulnerable to infectious diseases and must live in a completely sterile environment. The most famous case is the boy David Vetter. SCID affects about 1 in 80,000 live births.

These babies usually die within 1 year due to severe, recurrent infections. Chronic diarrhea, recurrent Pneumocystis jiroveci pneumonia and profuse oral candidiasis commonly occur.

IL-7 signalling pathway

Most cases of SCID are derived from mutations in the γ_c chain in the receptors for interleukins IL-2, IL-4, IL-7, IL-9 and IL-15. These interleukins and their receptors form part of the IL-7 signalling pathway.

The IL-2 receptor γ (IL-2Rγ) gene is located on the X chromosome and mutation of this gene causes X-linked SCID.

Janus kinase-3 (JAK3) is an enzyme that mediates transduction of the γ_c signal. Mutation of its gene also causes SCID.

VDJ recombination

The manufacture of immunoglobulins requires recombinase enzymes derived from the recombination activating genes RAG-1 and RAG-2. These enzymes undertake splicing of exons V, D and J segments of the κ light chain within B-cells. Severe mutation within RAG-1 or RAG-2 causes SCID.

Adenosine deaminase

Another well-known form of SCID is caused by a defective enzyme, adenosine deaminase (ADA), necessary for the breakdown of purines. Lack of ADA causes accumulation of dGTP. This metabolite is toxic to lymphoid stem cells.

Treatment

The most common treatment for SCID is bone marrow transplantation, which requires matched donors. David Vetter, the original "bubble boy," endured several failed transplantations, and finally passed away after he decided to enter the outside world.

More recently, gene therapy has proved useful. Transfection of the missing gene using viral vectors is especially useful in ADA SCID and X-linked SCID.

Example Usage of Deficiency