Therapy in adenosine deaminase and purine nucleoside phosphorylase deficient patients

Abstract

The discovery of the causal association of adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) deficiency with some forms of primary immunodeficiency disease had led to new approaches to therapy, such as enzyme replacement. In ADA deficiency, bone marrow transplantation remains the primary method of choice. If no suitable bone marrow donor is available, enzyme replacement with irradiated erythrocyte transfusions should be considered. The latter therapy may be sustained by treatment with thymic factors. In ADA deficiency, bone marrow transplantation and, in about 50% of the cases, also enzyme replacement, may result in clinical and neurological improvement with concurrent (partial) restoration of immune function and (partial) disappearance of the metabolic abnormalities present before treatment. In PNP deficiency, enzyme replacement has been evaluated carefully in only two patients. The results disclose profound changes in the purine excretion patterns after each transfusion, and a slow but partial restoration of in vitro T cell function. Treatment of ADA and PNP deficiency with continued enzyme replacement by erythrocyte transfusions has certain risks which hopefully can be overcome in the near future by loading the patient's own blood cells with the missing enzyme.