Enzyme Replacement Therapy for Adenosine Deaminase Deficiency and Severe Combined Immunodeficiency

To evaluate their role as a form of replacement therapy, frozen irradiated red blood cells were administered to a child with adenosine deaminase deficiency associated with severe combined immunodeficiency disease. In vitro lymphocyte responses to mitogens and allogeneic cells were restored. Subsequently, a “thymus shadow” appeared, and immunoglobulin synthesis was demonstrated. Frozen irradiated plasma, which alone had no effect on lymphocyte numbers or responses, promoted lymphocytosis when given with frozen irradiated red blood cells. The patient received the transfusions with or without irradiated plasma at four-week intervals and remained free of infection for 17 months. The patient's lymphocyte adenosine triphosphate levels were elevated before therapy, which consistently reduced them without altering the lymphocyte adenosine deaminase activity. Enzyme replacement therapy may provide a way to treat patients with adenosine deaminase deficiency associated with severe combined immunodeficiency disease who do not have histocompatible bone-marrow donors. (N Engl J Med 295:1337-1343, 1976). Severe combined immunodeficiency disease is characterized by the absence of both humoral and cell-mediated immunity. Affected infants manifest lymphopenia, thymic aplasia or hypoplasia and absence of delayed hypersensitivity as well as defective immunoglobulin and antibody synthesis. Their lymphocytes do not respond in vitro to mitogens or antigens, including allogeneic cells. If immunologic reconstitution cannot be achieved, patients with the disease invariably die of infection, usually before two years of age. Histocompatible bone-marrow transplantation has been successful in establishing immunocompetence for infants with this disorder.₁When histocompatible donors have not been available, transplantation with fetal thymus or fetal liver has been.