2026-07-07 | Anifrolumab, a potential treatment for ADA2 deficiency.
Adenosine deaminase 2 deficiency (DADA2) is an inborn error of immunity leading to systemic vasculitis, haematological manifestations, immune deficiency and/or autoimmunity. We report the case of a 26-year-old female with an initial diagnosis of systemic lupus erythematosus (SLE). However, atypical evolution patterns for SLE (hypogammaglobulinaemia, moderate B-cell lymphopenia, disappearance of anti-dsDNA) led to the identification of a homozygous class 5 missense variant of CECR1/ADA2, thus to a final diagnosis of DADA2. Strikingly, the patient was treated with anifrolumab (an anti-interferon alpha receptor 1 antibody) that rapidly induced clinical remission and significant corticosteroid tapering. Consistently, we show a lower type I interferon (IFN-I) score and a persistently low tumour necrosis factor α (TNFα) and IL-6 expression levels in whole blood cells of the patient during anifrolumab compared to anti-TNFα. Altogether, this case (1) illustrates the challenging diagnosis of DADA2 (SLE with hypogammaglobulinaemia) and (2) reinforces DADA2 as a disease at the border with type I interferonopathies. Besides, we report here, to our knowledge, the first description of a successful use of anifrolumab in DADA2, paving the way for further studies to validate this therapeutic approach.
Open article ↗
2026-06-01 | First Case of Deficiency of Adenosine Deaminase 2 (DADA2) in Oman With a Novel Mutation: A Case Report.
Deficiency of adenosine deaminase 2 (DADA2) is a rare autosomal recessive disorder that results from biallelic loss-of-function mutations in the ADA2 gene. It is characterized by a spectrum of clinical features, predominantly vasculitis, autoinflammation, dysregulated immune function, and hematologic abnormalities, making it a challenging condition to diagnose. This case report presents the first documented case of DADA2 in Oman, highlighting a novel mutation in the ADA2 gene. It provides insights into the diagnostic process, therapeutic strategies, systemic evaluations, and family-focused management, contributing to the growing understanding of this rare disorder. This is a case of an 18-month-old male toddler who presented with persistent bi-cytopenia and a history of febrile seizures. Genetic testing revealed a novel homozygous pathogenic variant in the ADA2 gene. The patient was managed with infliximab infusions and regular follow-up. This report enhances the understanding of DADA2. The identification of a novel mutation in this case further highlights the growing insight into the pathogenesis of DADA2 and its clinical implications. Effective management requires genetic testing, systemic evaluation, and targeted therapy. Genetic counseling and family screening are crucial for early intervention and disease prevention. Further research is needed to improve diagnostics, treatments, and patient outcomes.
Open article ↗
2026-05-26 | Deficiency of Adenosine Deaminase 2 (DADA2): A Single-Center Experience with Diverse Clinical Phenotypes and Outcomes
Background 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. Objective To describe the clinical phenotypes, laboratory features, genetic variants, treatment patterns, and outcomes of patients with DADA2 at a national referral center. Methods 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. Results 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). Conclusion 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.
Open article ↗
