Long-Term Outcome of Adenosine Deaminase-Deficient Patients—a Single-Center Experience
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Inherited defects in the adenosine deaminase (ADA) enzyme can cause severe combined immune deficiency (SCID) and systemic abnormalities. Management options for ADA-deficient patients include enzyme replacement therapy (ERT), hematopoietic stem cell transplantation (HSCT), and gene therapy (GT). Here, we describe the long-term benefits of these treatments.
Survival, infections, systemic sequelae, and laboratory assessments were recorded for all ADA-deficient SCID patients, managed at a single center since 1985, who survived 5 or more years following treatment.
Of 20 ADA-deficient patients, the 8 (40%) who survived 5 or more years (range 6–29.5 years, median 14 years) were included in the study. Among the long-term survivors, two patients were treated exclusively with ERT, five underwent HSCT (three from HLA-matched sibling donors, two from HLA-mismatched related donors), and one received GT. The long-term survivors often suffered from recurrent respiratory infections; however, opportunistic infections occurred in only one patient. Systemic sequelae included lung disease such as bronchiectasis and asthma (four patients), neurologic abnormalities (six patients), metabolic disturbances (two patients), allergy and autoimmunity (six patients), and neoplasms (three patients). Normal CD4+ T cell numbers and function, as well as antibody production, were usually observed after HSCT and GT, but not after ERT. Late deaths occurred in two patients at 15 and 25 years after HSCT, respectively, and were attributed to respiratory failure.
ADA-deficient patients commonly suffer from long-term complications, emphasizing the need for improved management and for multi-disciplinary follow-up.
KeywordsImmune deficiency adenosine deaminase bone marrow transplant enzyme replacement gene therapy PEG-ADA
Total deoxyadenosine nucleotides
Enzyme replacement therapy
Hematopoietic stem cell transplant
HLA-mismatched related donors
HLA-matched sibling donor
HLA-matched unrelated donors
Severe combined immune deficiency
The authors thank Dr. Chaim M. Roifman for his contributions to the diagnosis and management of the patients as well as the development of this manuscript. This work was supported in part by The Donald and Audrey Campbell Chair for Immunology (EG).
Compliance with Ethical Standards
Conflict of Interest
AA is the principal investigator of the ADA-SCID gene therapy clinical trial with gamma-RV; the gene therapy was licensed to GlaxoSmithKline (GSK) in 2010 and GSK became the financial sponsor of the clinical trial. Other authors disclose no conflicts of interest.
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