ADA-SCID and its causes

ADA-SCID is a specific form of severe combined immunodeficiency (SCID). It is inherited as an autosomal recessive condition. This means that a child has to inherit the faulty gene from both parents to have the condition. There may be a family history of previously affected children, particularly if there are first or second cousin marriages or partnerships in the family. More information about autosomal recessive inheritance can be found in our leaflet Genetic aspects of immunodeficiency.

What causes it?

ADA-SCID is caused by mistakes (mutations) in the ADA gene, which result in
absent or very low levels of the enzyme ADA. Enzymes are protein substances
that help speed up chemical reactions in the body. Lack of the ADA enzyme
causes a build-up of a toxic substance called deoxyadenosine. This prevents cells
from dividing effectively.

White blood cells (especially lymphocytes, and more specifically T cells, B cells and natural killer (NK) cells) that are important for a healthy immune system are very sensitive to these toxic effects and fail to develop normally, leading to SCID.

However, the ADA gene is important in all cells of the body, and therefore patients with ADA-SCID often also have symptoms and signs outside the immune system. In some cases there may be a low level of working ADA enzyme, leading to a less severe ‘delayed’ onset of combined immune deficiency (CID) – please refer to our separate information on CID.

Reviewed February 2018