Adenosine deaminase
(ADA) deficiency
Three different options of treatment
Another type of SCID is caused by mutations in a gene that encodes an enzyme (protein) called Adenosine deaminase. This enzyme is essential for the metabolic function of a variety of body cells, but especially T-cells.
The absence of this enzyme leads to an accumulation of toxic metabolic by-products within lymphocytes that cause the cells to die. ADA deficiency is the second most common cause of SCID, accounting for 15-20% of cases. Babies with this type of SCID have the lowest total lymphocyte counts of all, and T, B and NK-lymphocyte counts are all very low. This form of SCID is inherited as an autosomal recessive trait. Both boys and girls can be affected.
1. Allogeneic HSCT from matched sibling and family donors is the treatment of choice for ADA-SCID while survival is significantly reduced in transplant from matched unrelated (66%) or haploidentical donors (43%). For patients who survive transplant, long-term immune response recovery is achieved.
2. Enzyme replacement therapy (ERT) with PEG-ADA therapy is well tolerated and can restore immune function to protective levels, long-term follow-up suggests an incomplete immune recovery with progressive decline over time.
3. Gene therapy with ADA-transduced autologous stem/progenitor cells represents an alternative option for ADA-SCID patient.
ADA deficiency was an ideal target for the first gene therapy trials for a number of reasons:
• the pathological effects of the disease are reversible
• the disease results from the loss of function of a single gene
• ADA levels vary widely in the normal population so tight control of the introduced gene is not important
• the ADA gene is very small and easy to manipulate in the laboratory
• the target cells for the therapy are lymphocytes, which are accessible, easy to culture and easy to put back into the body of the patient
• the alternative treatments are expensive and/or hazardous.
