AUTOINFLAMMATORY DISEASES IN HEMATOLOGY FROM DIAGNOSIS TO TREATMENT

AUTOINFLAMMATORY_DISEASES_IN_HEMATOLOGY_FROM_DIAGNOSIS_TO_TREATMENTkapak

DEFICIENCY OF ADA 2 (DADA2)

Gül Yavuz Ermiş

University of Health Sciences, Gülhane Training and Research Hospital, Department of Hematology, Ankara, Türkiye

Yavuz Ermiş G. Deficiency of ADA2 (DADA2). In: Kurt Yüksel M, editor. Autoinflammatory Diseases in Hematology from Diagnosis to Treatment. 1st ed. Ankara: Türkiye Klinikleri; 2025. p.59-68.

ABSTRACT

Adenosine deaminase 2 (DADA2) deficiency is an autosomal recessive disorder caused by loss-offunction (LOF) mutations in the ADA2 gene (formerly known as CECR1 (the cat eye syndrome chromosome region, candidate 1) gene). It was first identified in 2014 as a monogenic vasculopathy or vasculitis closely resembling polyarteritis nodosa (PAN). The primary manifestations of the condition occur during childhood, with the most evident clinical presentation resembling systemic vasculitis similar to PAN. Characteristic findings include both cutaneous and neurological abnormalities, as well as immunological and hematological abnormalities.

Deficiency of ADA2 enzyme leads to macrophage polarization and differentiation, triggering the release of inflammatory cytokines. Additionally, chronic neutrophil activation and dysregulated NET (neutrophil extracellular traps) osis play a critical role in the pathogenesis. Diagnosis should be considered in patients presenting with systemic vasculitis, immunodeficiency, and hematological abnormalities based on clinical and laboratory findings. Diagnosis requires demonstrating ADA2 enzyme deficiency and/or genetic testing.

Anti-TNF therapies effectively address vasculitic symptoms, especially by preventing new neurological ischemic events. Early initiation of these therapies has been associated with better prognosis. Allogeneic hematopoietic stem cell transplantation (HSCT) remains the most effective and definitive treatment for all phenotypes, though transplant-related complications and graft failure should not be disregarded.

Keywords: Deficiency of adenosine deaminase 2; Red-cell aplasia, pure; Stroke; Tumor necrosis factor inhibitors

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