Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive autoinflammatory and immunodysregulatory disorder characterized by vasculopathy, cytopenias, and variable immune dysfunction. Its expanding phenotypic spectrum continues to challenge early recognition and timely intervention.
To describe the clinical phenotypes, laboratory features, genetic variants, treatment patterns, and outcomes of patients with DADA2 at a national referral center.
We conducted a retrospective review of all genetically confirmed DADA2 cases evaluated over a 5-year period at the Pediatric Allergy, Immunology, and Rheumatology Division at Queen Rania Children’s Hospital (Amman, Jordan). Demographic, clinical, laboratory, and genetic data were extracted, and therapeutic exposures and outcomes were analyzed.
10 patients (7 females, 3 males) were identified, all with homozygous pathogenic variants. The c.1471_1472dup mutation was predominant (7/10). The mean age at presentation was 63.7 ± 59.2 months, and the median diagnostic delay was 24.5 months (interquartile range 64.5). Fever was universal, and immune dysregulation was common, including vasculopathy, skin involvement, lymphoproliferation, and cytopenias. Recurrent infections occurred in only three patients. The mean ADA2 level was 1.5 mU/g protein. Two previously unreported phenotypes were observed: nonimmune hydrops fetalis and chronic pancreatitis. Treatments included corticosteroids (10/10), intravenous immunoglobulin (6/10), cyclosporine (6/10), G-CSF (7/10), mycophenolate mofetil (2/10), sirolimus (1/10), anti-TNF therapy (8/10), and hematopoietic stem cell transplantation (3/10). Overall mortality was 40%, with deaths due to sepsis (2), stroke (1), and transplant-related complications (1).
DADA2 demonstrates marked phenotypic heterogeneity with substantial diagnostic delays. Recognition of atypical presentations, including hydrops fetalis and chronic pancreatitis, may broaden the known disease spectrum. Early diagnosis and timely initiation of anti-TNF therapy or hematopoietic stem cell transplantation remain critical for improving outcomes.
