Adenosine deaminase (ADA) deficiency is the second most common cause of severe combined immunodeficiency (SCID), leading to progressive T, B, and natural killer cell lymphopenia due to toxic metabolite accumulation. Early diagnosis, continuous monitoring, and timely intervention are critical to preventing irreversible complications, even in patients undergoing bone marrow transplantation (BMT).
We present three patients with ADA-SCID managed with BMT and enzyme replacement therapy (ERT) posttransplant, demonstrating distinct therapeutic approaches and long-term outcomes. Patient 1, a 27-year-old female, underwent maternal HSCT at 1 month of age, achieving partial T cell engraftment but absent B cell recovery. Delayed initiation of ERT with elapegademase in adulthood improved biochemical markers but failed to prevent severe complications, including autoimmunity, neurocognitive decline, and adrenal insufficiency. Patient 2, a 26-year-old female, received multiple interventions including failed haploidentical HSCT and two autologous gene therapy infusions in early childhood. Due to limited engraftment, she required long-term ERT, transitioning from pegademase to elapegademase. Despite sustained deoxyadenosine nucleotide suppression, she developed chronic lung disease, metabolic dysfunction, and immune dysregulation. Patient 3, a 3-year-old female, was diagnosed through newborn screening and initiated on pretransplant ERT before undergoing matched unrelated donor HSCT at 11 months. Despite early intervention, she experienced graft failure and is currently maintained on elapegademase.
This series highlights the clinical heterogeneity of ADA-SCID and underscores the critical, long-term role of ERT, not only as a bridge to definitive therapy but also as an essential ongoing treatment in cases of incomplete or failed engraftment. While early HSCT or gene therapy offers curative potential, delays or failures can result in irreversible damage. These cases emphasize the importance of universal newborn screening and sustained access to ERT, particularly in resource-limited settings.
