Amelioration of Neurologic Abnormalities after Enzyme Replacement in Adenosine Deaminase Deficiency

Abstract

INHERITED deficiency of the purine salvage enzyme adenosine deaminase (ADA) results in the fatal infantile syndrome of severe combined immunodeficiency.^{1 2 3 4} The accumulation of the purine substrates of ADA, adenosine and deoxyadenosine and their metabolites, including deoxyadenosine triphosphate (deoxy ATP) and cyclic AMP, appears to provide pathophysiologic mechanisms for lymphoid toxicity.^{5 6 7 8 9 10} Children with severe combined immunodeficiency due to ADA deficiency are generally indistinguishable clinically from patients with severe combined immunodeficiency of other origins, ^{2 3 4} but they may have several additional nonimmunologic abnormalities. Bony abnormalities are found in a substantial proportion of ADA-deficient patients, ^{2 3 4 , 11} and in vitro abnormalities of platelet function have been . . .