Background/Purpose: Deficiency of adenosine deaminase 2 (DADA2), described in 2014, is  characterized by intermittent fevers, early-onset lacunar strokes, livedoid rash, hepatosplenomegaly, systemic vasculopathy, and/or immunodeficiency. Given the rarity, recent discovery, and clinical heterogeneity of DADA2, we aimed to characterize its demographic and clinical spectrum within our institution to enhance recognition and guide management strategies. Here, we describe patients with a wide variety of ages and features at presentation.

Methods: A retrospective chart review was conducted of patients diagnosed with DADA2 followed at Texas Children’s Hospital (TCH) between 2014 and 2025. A total of eight patients were included in the study. Of the included patients, 63% were female and 37% were male. Data were obtained from the TCH electronic medical record system, Epic. Variables collected included demographic characteristics, ADA2 mutation analysis, ADA2 enzyme activity levels, clinical manifestations, and treatment regimens. Descriptive statistics were used to summarize the data.

Results: Eight patients with DADA2 were identified between 2014–2025. The median age at diagnosis was 12 years (range: 7 months–20 years). Common presentations included livedo reticularis (50%), recurrent fevers (38%), and arthralgia/fatigue (25%); one patient (12.5%) presented with recurrent strokes. All patients had biallelic pathogenic or likely pathogenic ADA2 variants, most frequently c.506G >A (p.Arg169Gln) and c.962G >A (p.Gly323Glu), with enzyme activity markedly reduced (0.1–1.4 mU/mL). (Table 1 ) Anti-TNF therapy, primarily adalimumab (75%), led to clinical improvement or stabilization in most cases. Two patients required hematopoietic stem cell transplantation for severe disease. No major treatment-related complications occurred.
 

Conclusion: DADA2 is a rare, recently recognized autoinflammatory disease with heterogeneous presentations ranging from livedo and recurrent fevers to strokes and cytopenias. Early diagnosis through genetic testing is essential to prevent irreversible complications. Anti-TNF therapy is effective and well-tolerated, while stem cell transplantation offers a potential cure for severe or immunodeficient cases. Awareness of this rare disease will lead to early diagnosis, treatment, and better patient outcomes.

« Back to 2026 Pediatric Rheumatology Symposium

ACR Meeting Abstracts - https://acrabstracts.org/abstract/demographics-and-clinical-features-of-deficiency-of-adenosine-deaminase-2-a-large-quaternary-single-center-experience/