Two siblings with adenosine deaminase deficiency were studied before and during “enzyme replacement” therapy (partial exchange transfusions with normal red cells containing the missing enzyme). The younger sib showed improvement of immunologic function during red-cell therapy alone, whereas in the older sib this improvement occurred only when the transfusions were supplemented by thymosin injections. Their clinical courses correlated with in vitro findings: lymphocytes from the younger sib differentiated to T-cell-rosette-forming cells upon addition of adenosine deaminase alone; lymphocytes from the older sibling required supplemental thymosin to form these cells. Thymic factors appear to influence the response to transfusion therapy in some patients deficient in adenosine deaminase, and supplementation of red-cell transfusion with thymic factors may be required. (N Engl J Med 300:387–392, 1979) IN most children with adenosine deaminase deficiency a severe, fatal immunodeficiency develops.1 2 3 4 5 Although they may have some residual immunocompetence at birth,3 it rapidly diminishes. The processes by which progressive immunologic attrition occurs are poorly understood. It has been proposed that the accumulated purine metabolites, such as deoxyadenosine, adenosine or deoxy ATP are directly cytotoxic to lymphocytes as well as inhibitory to proliferation, differentiation and maturation of immunocompetent cells.6 7 8 9 10 Thus, addition of adenosine or deoxyadenosine to cultures of normal human lymphocytes11,12 or of lymphoblast cell lines6,13 in the presence of an adenosine deaminase inhibitor impairs cell proliferation. Addition of the enzyme.
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