Adenosine deaminase deficiency: enzyme replacement therapy and investigations of the biochemical basis of immunodeficiency

Abstract

In 1972, Giblett and co-workers¹ and Dissing and Knudsen² reported the coexistence of adenosine deaminase (ADA) deficiency and severe combined immunodeficiency disease (SCID). The discovery of an association between deficiency of an enzyme and an immunodeficiency represents a major conceptual landmark in that we now recognize that at least some immunodeficiency diseases, ‘experiments of nature’ as Dr Robert A. Good so elegantly called them, may indeed be inborn errors of metabolism’ whose major consequences are manifest in the function of the immune system³. Therefore, if some immunodeficiencies are indeed metabolic diseases, the diagnostic and therapeutic approaches to these disorders must be similar to our approach to metabolic diseases, namely biochemical and pharmacological. Rational approaches to therapy presupposes an understanding of the biochemical basis of the immune dysfunction. This paper describes some of our investigations into the adenosine deaminasedeficient form of severe combined immunodeficiency disease, as well as our experience with enzyme replacement therapy for this disorder and some recent studies with pharmacological agents upon adenosine deaminase-deficient lymphocytes.