This study will monitor the long-term effects of gene therapy in patients with severe
combined immunodeficiency disease (SCID) due to a deficiency in an enzyme called adenosine
deaminase (ADA). It will also follow the course of disease in children who are not
receiving gene therapy, but may have received enzyme replacement therapy with the drug
ADA is essential for the growth and proper functioning of infection-fighting white blood
cells called T and B lymphocytes. Patients who lack this enzyme are, therefore, immune
deficient and vulnerable to frequent infections. Injections of PEG-ADA may increase the
number of immune cells and reduce infections, but this enzyme replacement therapy is not a
definitive cure. In addition, patients may become resistant or allergic to the drug. Gene
therapy, in which a normal ADA gene is inserted into the patient's cells, attempts to
correcting the underlying cause of disease.
Patients with SCID due to ADA deficiency may be eligible for this study. Patients may or
may not have received enzyme replacement therapy or gene transfer therapy, or both.
Participants will have follow-up visits at the National Institutes of Health in Bethesda,
Maryland, at least once a year for a physical examination, blood tests, and possibly the
following additional procedures to evaluate immune function:
1. Bone marrow sampling - A small amount of marrow from the hip bone is drawn (aspirated)
through a needle. The procedure can be done under local anesthesia or light sedation.
2. Injection of small amounts of fluids into the arm to study if the patient's lymphocytes
3. Administration of vaccination shots.
4. Collection of white blood cells through apheresis - Whole blood is collected through a
needle placed in an arm vein. The blood circulates through a machine that separates it
into its components. The white cells are then removed, and the red cells, platelets
and plasma are returned to the body, either through the same needle used to draw the
blood or through a second needle placed in the other arm.
5. Blood drawings to obtain and study the patient's lymphocytes.
The primary purpose of this study is to continue to provide clinical follow-up for
ADA-deficient patients treated with gene therapy under the original protocol 90-HG-0195 (IND
3624) and its amendments (IND 4647 and IND 5056). The objectives are the long-term
monitoring of the beneficial effects of gene therapy and continued surveillance of potential
adverse effects associated with the gene transfer procedures.
No new subjects will be enrolled in this protocol.
New patients will not be treated under protocol 90-HG-0195 as new and improved vectors and
technologies have become available in the recent years.
New patients with ADA deficiency, however, may be enrolled in protocol 90-HG-0195 for
clinical evaluation of their immune system and pre-treatment testing of transduction