ArticleThe Journal of allergy and clinical immunology2020
Genotype and functional correlates of disease phenotype in deficiency of adenosine deaminase 2 (DADA2).
Article in The Journal of allergy and clinical immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 2 of them syntheses that pooled it.
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Who cites it
76 citing papers in PubMed, 2 syntheses or guidelines pooled it, 145 citations in OpenAlex.
- A wide spectrum of phenotype of deficiency of deaminase 2 (DADA2): a systematic literature review.Orphanet journal of rare diseases · 2023Pooled it
- Clinical and Therapeutic Aspects of Sideroblastic Anaemia with B-Cell Immunodeficiency, Periodic Fever and Developmental Delay (SIFD) Syndrome: a Systematic Review.Journal of clinical immunology · 2023Pooled it
- Advancements in Diagnosis and Care for Immune Dysregulation and Inborn Errors of Immunity in Pediatric Rheumatology: Our 50-Year Journey.Arthritis care & research · 2026Review
- ADA2 genotype and enzyme activity may predict vasculitic or hematologic DADA2 phenotype.Journal of human immunity · 2026Article
- Adenosine deaminase type 2 deficiency: From rare to common.Journal of human immunity · 2026Review
- DADA2 as a Model of Monogenic Immune Vasculopathy: From Immunopathogenesis to Precision Therapeutics.Biomolecules · 2026Review
- First Case of Deficiency of Adenosine Deaminase 2 (DADA2) in Oman With a Novel Mutation: A Case Report.Cureus · 2026Article
- ADA2-deficient cells exhibit increased levels of cell death and metabolic disturbances.Cell death discovery · 2026Article
- Diagnostic Implications and Correlates of Plasma Adenosine Deaminase 2 Activity and ADA2 Variants.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Pure Red Cell Aplasia Associated with ADA2 Gene Mutation.Indian journal of pediatrics · 2026Article
- A Review of Adenosine Deaminase 2 (ADA2) as a Biomarker of Monocyte/Macrophage Activation.Current allergy and asthma reports · 2026Review
- Gene therapy supports long-term reconstitution of patient hematopoietic stem cells in deficiency of adenosine deaminase 2.Molecular therapy. Methods & clinical development · 2025Article
- Preclinical evaluation of lentiviral gene therapy for adenosine deaminase 2 deficiency (DADA2): engraftment efficiency and biodistribution in humanised NBSGW mice.Gene therapy · 2025Article
- Dominant negative ADA2 mutations cause ADA2 deficiency in heterozygous carriers.The Journal of experimental medicine · 2025Article
- The pathogenesis, clinical presentations and treatment of monogenic systemic vasculitis.Nature reviews. Rheumatology · 2025Review
- Getting to know adenosine deaminase 2 deficiency inside and out.The Journal of allergy and clinical immunology · 2025Review
- Extreme Phenotypic Variation in Siblings with Identical Homozygous Mutations Causing ADA2 Deficiency: A Case SeriesTurkish journal of haematology : official journal of Turkish Society of Haematology · 2025Article
- Early-onset neutropenia and mixed phenotype in ADA2 deficiency: diagnostic and therapeutic challenges.Frontiers in immunology · 2025Article
- Misdiagnosed for 14 Years: Adenosine Deaminase 2 (ADA2) Deficiency in a Teen Mimicking Polyarteritis Nodosa.Clinical case reports · 2024Article
- Rare primary vasculitis: update on multiple complex diseases and the new kids on the block.Advances in rheumatology (London, England) · 2024Review
16 more citing papers are in PubMed but not listed here.
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Authors and funding
31 authors at 17 institutions in 10 countries.
Funding
Abstract
backgroundDeficiency of adenosine deaminase 2 (DADA2) is a syndrome with pleiotropic manifestations including vasculitis and hematologic compromise. A systematic definition of the relationship between adenosine deaminase 2 (ADA2) mutations and clinical phenotype remains unavailable.
objectiveWe sought to test whether the impact of ADA2 mutations on enzyme function correlates with clinical presentation.
methodsPatients with DADA2 with severe hematologic manifestations were compared with vasculitis-predominant patients. Enzymatic activity was assessed using expression constructs reflecting all 53 missense, nonsense, insertion, and deletion genotypes from 152 patients across the DADA2 spectrum.
resultsWe identified patients with DADA2 presenting with pure red cell aplasia (n = 5) or bone marrow failure (BMF, n = 10) syndrome. Most patients did not exhibit features of vasculitis. Recurrent infection, hepatosplenomegaly, and gingivitis were common in patients with BMF, of whom half died from infection. Unlike patients with DADA2 with vasculitis, patients with pure red cell aplasia and BMF proved largely refractory to TNF inhibitors. ADA2 variants associated with vasculitis predominantly reflected missense mutations with at least 3% residual enzymatic activity. In contrast, pure red cell aplasia and BMF were associated with missense mutations with minimal residual enzyme activity, nonsense variants, and insertions/deletions resulting in complete loss of function.
conclusionsFunctional interrogation of ADA2 mutations reveals an association of subtotal function loss with vasculitis, typically responsive to TNF blockade, whereas more extensive loss is observed in hematologic disease, which may be refractory to treatment. These findings establish a genotype-phenotype spectrum in DADA2.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.