Enzyme Replacement Therapy for Adenosine Deaminase Deficiency and Severe Combined Immunodeficiency

TLDR

The study evaluated frozen irradiated red blood cells as a replacement therapy for a child with adenosine deaminase deficiency and severe combined immunodeficiency. The therapy involved transfusing frozen irradiated red blood cells, with or without frozen irradiated plasma, to stimulate lymphocyte recovery. The treatment restored lymphocyte function, induced thymic activity and immunoglobulin production, kept the patient infection‑free for 17 months, lowered lymphocyte ATP levels, and suggests enzyme replacement therapy as a viable option for ADA‑deficient SCID patients lacking compatible bone‑marrow donors.

Abstract

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 lymphocytes 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.