Deficiency of Adenosine Deaminase-2 (DADA-2): A Rare Cause of Recurrent Stroke in Young

Abstract

Deficiency of adenosine deaminase 2 (DADA-2) is a rare, recessively inherited disorder caused by mutations in the ADA2 gene, leading to a deficiency of the enzyme adenosine deaminase-2. This enzyme plays a crucial role in immune regulation and endothelial function, and its deficiency results in a monogenic syndrome characterized by a diverse range of clinical manifestations, including autoinflammation, immunodeficiency, vasculopathy, early-onset stroke, and hematological abnormalities. We present the case of an adolescent female who, over the past one and a half years, has experienced recurrent episodes of periodic fever and neurological deficits, manifesting as ischemic strokes. Laboratory investigations revealed microcytic hypochromic anemia, lymphopenia with reduced natural killer (NK) cells, and elevated inflammatory markers. Genetic testing identified a homozygous pathogenic mutation in the ADA2 gene, confirming the diagnosis of DADA-2.

The patient was initially treated with a daily dose of oral colchicine (0.6 mg twice daily). Subsequently, infliximab, a tumor necrosis factor alpha (TNF-α) inhibitor, was introduced to address the refractory symptoms. On follow-up, the patient showed a favorable response, with no further strokes and resolution of the fever, indicating successful management of the disease. This case highlights the importance of early recognition of DADA-2, especially in young patients presenting with recurrent strokes and autoinflammatory symptoms, as genetic testing is crucial for diagnosis. The use of colchicine and biologic agents, such as infliximab, has proven to be effective in controlling inflammation, preventing vascular complications, and improving patient outcomes.