Adenosine deaminase deficiency (ADA) is a rare, inherited disorder of
purine metabolism characterized by immunodeficiency,
failure to thrive and metabolic abnormalities. A lack of the
enzyme ADA allows accumulation of toxic metabolites causing defects of both cell mediated and humoral immunity leading to ADA
severe combined immune deficiency (SCID), a condition that can be fatal in early infancy if left untreated. Hematopoietic stem cell transplant is curative but is dependent on a good donor match. Other therapeutic options include
enzyme replacement therapy (ERT) with
pegademase bovine (
PEG-ADA) and more recently gene therapy.
PEG-ADA has been used in over 150 patients worldwide and has allowed stabilization of patients awaiting more definitive treatment with hematopoietic stem cell transplant. It affords both metabolic detoxification and protective immune function with patients remaining clinically well, but immune reconstitution is often suboptimal and may not be long lived. We discuss the pharmacokinetics, immune reconstitution, effects on systemic disease and side effects of treatment with
PEG-ADA. We also review the long-term outcome of patients receiving ERT and discuss the role of
PEG-ADA in the management of infants and children with
ADA-SCID, alongside other therapeutic options.