Deficiency of Adenosine Deaminase 2 (DADA2) — Comprehensive Disease Characteristics Report

Executive summary

Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive inborn error of immunity caused by biallelic loss-of-function variants in ADA2 (formerly CECR1) and characterized by a triad of (i) vasculitis/vasculopathy with early-onset ischemic and hemorrhagic strokes and cutaneous vasculopathy, (ii) immune dysregulation/immunodeficiency, and (iii) hematologic disease including cytopenias and bone marrow failure. Large cohorts and meta-reviews show substantial neurologic burden (≈50% have a neurologic event), strong prevention of ischemic events with TNF inhibition, and curative potential of hematopoietic cell transplantation (HCT) for refractory hematologic/immunologic phenotypes. Recent 2024 mechanistic work implicates lysosomal ADA2 in DNA editing (dA→dI) and TLR9-mediated nucleic-acid sensing, expanding the classical extracellular-adenosine model. (dzhus2023anarrativereview pages 1-2, wouters2024humanada2deficiency pages 1-3, hashem2021hematopoieticcelltransplantation pages 1-2, cooray2021antitumournecrosisfactor pages 1-4, greinertollersrud2024ada2isa pages 1-3)

Table: This table condenses identifiers, genetics, core phenotype domains, diagnostics, and major treatment outcomes for DADA2. It is useful as a structured evidence scaffold for a disease knowledge base entry and can be supplemented with formal citations in the final report.

Table: This table summarizes major DADA2 phenotypes across key cohorts and reviews, with best-effort ontology mappings to HPO and UBERON terms. It is useful for structured knowledge-base curation of phenotype prevalence, affected anatomy, and ontology alignment.

1. Disease information

1.1 What is the disease? (concise overview)

DADA2 is a monogenic systemic autoinflammatory/vasculopathic disorder and inborn error of immunity caused by biallelic ADA2 loss-of-function variants, classically presenting with livedo racemosa/reticularis, polyarteritis nodosa (PAN)-like vasculitis, and recurrent lacunar ischemic strokes (often in early childhood), with expanding recognition of immune dysregulation and bone marrow failure phenotypes. (barron2022thespectrumof pages 1-2, wouters2024humanada2deficiency pages 1-3, dzhus2023anarrativereview pages 1-2)

1.2 Key identifiers

• MONDO: MONDO_0014306 (“deficiency of adenosine deaminase 2”). (OpenTargets Search: Deficiency of adenosine deaminase 2,DADA2-ADA2,CECR1)
• OMIM: 615688 (noted in a multinational HCT outcome cohort). (hashem2021hematopoieticcelltransplantation pages 1-2)
• Gene/target: ADA2 (ENSG00000093072). (OpenTargets Search: Deficiency of adenosine deaminase 2,DADA2-ADA2,CECR1)

Not available in retrieved sources: Orphanet ID, ICD-10/ICD-11 codes, MeSH identifier. These should be added from OMIM/Orphanet/ICD/MeSH directly in a follow-up curation pass.

1.3 Synonyms / alternative names

• Human ADA2 deficiency
• ADA2 deficiency
• CECR1 deficiency
• Deficiency of adenosine deaminase type 2 (ADA2 was formerly called CECR1). (wouters2024humanada2deficiency pages 1-3, hashem2021hematopoieticcelltransplantation pages 1-2)

1.4 Evidence source type

Evidence in this report derives from: - Aggregated cohorts and multicenter studies (NIH 60-patient cohort; Brazilian 18-patient cohort; multicenter anti-TNF and HCT outcome studies). (barron2022thespectrumof pages 1-2, melo2023abraziliannationwide pages 1-2, cooray2021antitumournecrosisfactor pages 1-4, hashem2021hematopoieticcelltransplantation pages 1-2) - Systematic/narrative literature review (628 reported patients). (dzhus2023anarrativereview pages 1-2, wouters2024humanada2deficiency pages 1-3) - Mechanistic primary research (Cell Reports 2024; zebrafish model 2024). (greinertollersrud2024ada2isa pages 1-3, brix2024ada2regulatesinflammation pages 1-2)

2. Etiology

2.1 Disease causal factors

Primary cause: biallelic loss-of-function variants in ADA2 (formerly CECR1) leading to absent or markedly reduced ADA2 enzymatic activity. (hashem2021hematopoieticcelltransplantation pages 1-2, wouters2024humanada2deficiency pages 3-4)

2.2 Risk factors

• Genetic risk factor (causal): autosomal recessive inheritance with homozygous/compound heterozygous ADA2 pathogenic variants. (dzhus2023anarrativereview pages 1-2, wouters2024humanada2deficiency pages 1-3)
• Consanguinity: prominent in some regional cohorts; e.g., 91% consanguineous parents in an Iranian case series. (ashari2023acaseseries pages 1-2)

Environmental risk factors: none established from retrieved sources.

2.3 Protective factors

Not established in retrieved sources.

2.4 Gene–environment interactions

Not established in retrieved sources.

3. Phenotypes

3.1 Phenotype spectrum and domains

A large NIH cohort proposes three overlapping phenotype “domains”: inflammatory/vascular, immune dysregulatory, and hematologic, with frequent overlap and phenotypic evolution over time. (barron2022thespectrumof pages 1-2)

3.2 High-value phenotype frequencies and characteristics (with HPO suggestions)

Selected quantitative phenotype frequencies are summarized in Artifact-01; key findings include:

Cutaneous/vascular

• Skin involvement reported in 52/58 (90%); livedo racemosa 43/58 (74%) in the NIH cohort. (barron2022thespectrumof pages 3-4)
• Brazilian cohort: mucocutaneous involvement 17/18 (94%), livedo reticularis 11/18 (62%). (melo2023abraziliannationwide pages 4-6)
• Iranian cohort: livedo racemosa/reticularis in 11/11 (100%). (ashari2023acaseseries pages 1-2)

HPO terms (examples): livedo reticularis/livedo racemosa; Raynaud phenomenon; skin ulcer. (barron2022thespectrumof pages 3-4, barron2022thespectrumof pages 8-10)

Neurologic

• NIH cohort: stroke in 25/58 (43%), including ischemic strokes 24/58 (41%) and hemorrhagic strokes 7/58 (12%); mean age at first stroke 5.7 years (range 0.4–20). (barron2022thespectrumof pages 3-4)
• Meta-review: 50.3% had ≥1 neurological event; among those with neurologic manifestations, 77.5% had ≥1 cerebrovascular accident; 35.9% had multiple strokes; ischemic stroke predilection for brainstem 37.3% and deep gray matter 41.6%. (dzhus2023anarrativereview pages 1-2)

HPO terms (examples): ischemic stroke; intracranial hemorrhage; lacunar infarct; seizures. (dzhus2023anarrativereview pages 1-2, barron2022thespectrumof pages 3-4)

Hematologic

• NIH cohort: cytopenia 28/58 (48%), pancytopenia 6/58 (10%), immune-mediated neutropenia 9/58 (16%), severe anemia 7/58 (12%), thrombocytopenia 5/58 (9%). (barron2022thespectrumof pages 4-7)

HPO terms (examples): pancytopenia; pure red cell aplasia; neutropenia; thrombocytopenia; bone marrow failure.

Immunologic

• NIH cohort: abnormal quantitative immunoglobulins 38/58 (66%) with low IgG 55%, low IgM 62%, low IgA 43%; low class-switched memory B cells 32/47 (68%); inadequate specific antibody responses 16/39 (41%). (barron2022thespectrumof pages 3-4, barron2022thespectrumof pages 8-10)

HPO terms (examples): hypogammaglobulinemia; decreased IgG/IgM/IgA; abnormal vaccine response.

Visceral/end-organ vasculitis

• NIH cohort: hepatomegaly 29/58 (50%), splenomegaly 31/58 (53%), portal hypertension 7/58 (12%), renal cortical lesions 13/58 (22%). (barron2022thespectrumof pages 3-4)
• Brazilian cohort: GI involvement 8/18 (45%) including abdominal pain 8/18 (45%) and colitis/GI ulcers 2/18 (12%). (melo2023abraziliannationwide pages 4-6)

Quality-of-life impact: NIH cohort noted severe sequelae after hemorrhagic strokes and moderate neuropsychological deficiencies on testing among evaluated patients; Brazilian cohort reports chronic sequelae/disabilities in 9/18 (50%). (barron2022thespectrumof pages 4-7, melo2023abraziliannationwide pages 4-6)

4. Genetic / molecular information

4.1 Causal gene(s)

• ADA2 (formerly CECR1). (hashem2021hematopoieticcelltransplantation pages 1-2, wouters2024humanada2deficiency pages 3-4)

4.2 Pathogenic variants

• Variants span multiple protein domains; most are missense, but splice/intronic and structural variants can occur and may require extended testing beyond standard exon sequencing. (wouters2024humanada2deficiency pages 3-4)
• Regional recurrence examples: Iranian cohort predominantly carried G47R (with one G321E case). (ashari2023acaseseries pages 1-2)

ClinVar/gnomAD allele frequencies: not extracted in retrieved sources.

4.3 Modifier genes, epigenetics, chromosomal abnormalities

Not established in retrieved sources.

5. Environmental information

Non-genetic environmental contributors were not identified in retrieved sources.

6. Mechanism / pathophysiology

6.1 Current mechanistic concepts (upstream→downstream causal chain)

A convergent model supported by recent reviews and primary research is: 1) Biallelic ADA2 loss-of-function → ADA2 deficiency (low/absent activity). (wouters2024humanada2deficiency pages 3-4, hashem2021hematopoieticcelltransplantation pages 1-2) 2) Myeloid skewing and inflammatory activation (monocytes/macrophages; M1 polarization) with cytokine outputs including TNF, along with reported type I/II interferon-stimulated gene signatures. (wouters2024humanada2deficiency pages 3-4, dzhus2023anarrativereview pages 1-2, barron2022thespectrumof pages 1-2) 3) Endothelial instability / impaired vascular integrity with perivascular inflammation → small/medium vessel disease, stenosis/aneurysm/occlusion → ischemia/infarction/hemorrhage (stroke; peripheral and visceral vasculopathy). (dzhus2023anarrativereview pages 1-2, wouters2024humanada2deficiency pages 3-4) 4) In parallel, hematopoietic defects (cytopenias; marrow failure) and immune dysfunction (hypogammaglobulinemia; low memory B cells; variable infection susceptibility). (barron2022thespectrumof pages 3-4, barron2022thespectrumof pages 1-2)

6.2 2024 mechanistic development: lysosomal ADA2, DNA editing, TLR9 sensing

A key 2024 Cell Reports study reports a major shift in ADA2 functional understanding, including the abstract statement: - “ADA2 localizes within the lysosomes…” and “ADA2 interacts with DNA molecules… converting deoxyadenosine (dA) to deoxyinosine (dI)…” and “…ADA2 regulate lysosomal immune sensing… by modulating TLR9 activation.” (greinertollersrud2024ada2isa pages 1-3)

This supports a cell-intrinsic innate immune mechanism linked to nucleic-acid sensing, potentially explaining interferon/TNF pathway activation beyond a purely extracellular adenosine model. (greinertollersrud2024ada2isa pages 1-3, wouters2024humanada2deficiency pages 4-5)

6.3 Model organism mechanistic evidence (2024 priority)

A 2024 zebrafish model study establishes cecr1b (ADA2-ortholog) loss-of-function with mechanistic resolution: - “Loss of Cecr1b disrupts hematopoietic stem cell specification… caused by induced inflammation in the vascular endothelium.” (brix2024ada2regulatesinflammation pages 1-2) - Rescue is shown by “blocking inflammation… modulation of the A2r pathway, or… recombinant human ADA2.” (brix2024ada2regulatesinflammation pages 1-2)

6.4 Implicated pathways (ontology suggestions)

• GO Biological Process (suggestions): inflammatory response; regulation of tumor necrosis factor production; type I interferon signaling pathway; response to interferon-gamma; regulation of endothelial cell integrity; hematopoietic stem cell differentiation; Toll-like receptor 9 signaling pathway.
• Cell Ontology (CL) (suggestions): monocyte; macrophage; neutrophil; endothelial cell; hematopoietic stem and progenitor cell; microglia (noted high expression of ADA2). (greinertollersrud2024ada2isa pages 1-3)
• CHEBI (suggestions): adenosine; inosine; deoxyadenosine; deoxyinosine. (greinertollersrud2024ada2isa pages 1-3, brix2024ada2regulatesinflammation pages 1-2)

7. Anatomical structures affected

7.1 Organ/system level

• Skin: livedo racemosa/reticularis, ulcers, necrosis. (barron2022thespectrumof pages 3-4, melo2023abraziliannationwide pages 4-6)
• Central nervous system: lacunar ischemic strokes and hemorrhagic strokes with predilection for brainstem and deep gray matter. (dzhus2023anarrativereview pages 1-2, barron2022thespectrumof pages 4-7)
• Hematopoietic system: bone marrow failure/cytopenias. (barron2022thespectrumof pages 4-7, hashem2021hematopoieticcelltransplantation pages 1-2)
• Liver/spleen: hepatomegaly, splenomegaly, portal hypertension. (barron2022thespectrumof pages 3-4, wouters2024humanada2deficiency pages 1-3)
• Kidney: renal cortical lesions. (barron2022thespectrumof pages 3-4)
• GI tract: abdominal pain, colitis/ulcers, and severe vasculitic intestinal injury in some cases. (melo2023abraziliannationwide pages 4-6, dzhus2023anarrativereview pages 1-2)

7.2 Tissue and cell level (CL suggestions)

Key implicated cells: myeloid lineage cells (monocytes/macrophages), neutrophils, and endothelial cells; zebrafish work links vascular endothelium inflammation to impaired hematopoietic stem cell emergence. (brix2024ada2regulatesinflammation pages 1-2, dzhus2023anarrativereview pages 1-2)

7.3 Subcellular level

Recent work places physiologically relevant ADA2 activity in the lysosome and implicates lysosomal nucleic-acid sensing via TLR9. (greinertollersrud2024ada2isa pages 1-3)

8. Temporal development

8.1 Onset

Typical onset is childhood: average onset 5–7 years; ~25% before age 1 and ~77% by age 10 in a 628-patient review, though adult-onset exists. (dzhus2023anarrativereview pages 1-2)

8.2 Progression/course

Course can be relapsing or progressive with recurrent ischemic events and evolving phenotype domains over time; NIH cohort emphasizes that phenotypes can evolve and overlap. (barron2022thespectrumof pages 1-2)

9. Inheritance and population

9.1 Inheritance

Autosomal recessive (biallelic loss-of-function variants). (dzhus2023anarrativereview pages 1-2, wouters2024humanada2deficiency pages 1-3)

9.2 Epidemiology

• Estimated carrier frequency ~1:236 and prevalence ~1:222,000 from modeling of residual ADA2 activity in vitro. (wouters2024humanada2deficiency pages 1-3)

9.3 Demographics (from literature review)

In a 628-patient review: among patients with known sex, ~46% female and 54% male; among reported ethnicities, ~50% Caucasian with representation from South Asia and the Middle East among others. (dzhus2023anarrativereview pages 1-2)

9.4 Founder effects / recurrent variants

Robust founder-effect mapping was not available in retrieved sources; however, regional recurrent variants were reported (e.g., G47R predominance in an Iranian series). (ashari2023acaseseries pages 1-2)

10. Diagnostics

10.1 Core diagnostic tests

A 2024 review states: “Identification of biallelic known pathogenic variants in ADA2… together with determination of severely diminished or absent ADA2 enzyme activity in the serum or plasma, is diagnostic.” (wouters2024humanada2deficiency pages 3-4)

10.2 ADA2 enzyme activity assays

Both HPLC and spectrophotometric assays are available for ADA2 activity measurement. (wouters2024humanada2deficiency pages 3-4)

10.3 Genetic testing approach

• Confirm biallelic ADA2 variants (single-gene testing, panels, or exome/genome approaches). (hashem2021hematopoieticcelltransplantation pages 1-2, wouters2024humanada2deficiency pages 3-4)
• Consider additional strategies for splice/intronic/structural variants when standard testing is inconclusive. (wouters2024humanada2deficiency pages 3-4)

10.4 Differential diagnosis

A recurring clinical issue is misdiagnosis as polyarteritis nodosa (PAN); DADA2 can constitute a significant fraction of pediatric early-onset PAN presentations in some series (as discussed in review context). (dzhus2023anarrativereview pages 1-2)

11. Outcome / prognosis

11.1 Mortality and severe outcomes

• Overall mortality estimated ~8%, mainly in childhood, in the 628-patient review. (dzhus2023anarrativereview pages 1-2)
• Brazilian cohort mortality 2/18 (12%). (melo2023abraziliannationwide pages 4-6)
• Major morbidity includes recurrent strokes (often multiple), hemorrhagic stroke sequelae, amputations for severe peripheral vascular disease, and neurocognitive deficits in subsets. (barron2022thespectrumof pages 4-7, barron2022thespectrumof pages 8-10)

11.2 Prognostic factors

Not fully resolved in retrieved sources; however, genotype–phenotype relationships have been proposed (absent activity variants correlating with marrow failure/PRCA vs residual activity correlating with vascular phenotypes). (wouters2024humanada2deficiency pages 3-4)

12. Treatment

12.1 Pharmacotherapy — TNF inhibition (real-world implementation)

Anti-TNF therapy is consistently supported as first-line disease-modifying therapy for the vasculitic/ischemic phenotype.

Quantitative outcomes (multicenter): In 31 genetically confirmed patients, anti-TNF reduced median CNS/non-CNS ischemic event rate from 2.37 per 100 patient-months pre-treatment to 0.00 per 100 patient-months post-treatment (p<0.0001) and reduced PVAS from 20/63 to 2/63. (cooray2021antitumournecrosisfactor pages 1-4)

Quantitative outcomes (NIH cohort): no strokes observed during 2026 patient-months on TNF inhibitors. (barron2022thespectrumof pages 1-2)

Limitations: Anti-TNF is generally not effective for severe immunodeficiency or bone marrow failure, which may require transplantation. (cooray2021antitumournecrosisfactor pages 1-4, wouters2024humanada2deficiency pages 3-4)

MAXO suggestions (best-effort): tumor necrosis factor inhibitor therapy; immunosuppressive therapy; biologic anti-inflammatory therapy.

12.2 Curative therapy — allogeneic hematopoietic cell transplantation (HCT/HSCT)

A multinational retrospective cohort (30 patients, 38 HCTs) reports strong outcomes: - 2-year overall survival 97% and 2-year GvHD-free relapse-free survival 73%; normalization of ADA2 activity in 16/17 tested; “no new vascular events”; and resolution of hematologic and immunologic phenotypes. (hashem2021hematopoieticcelltransplantation pages 1-2)

Indications: bone marrow failure, immune cytopenia, malignancy, or immunodeficiency. (hashem2021hematopoieticcelltransplantation pages 1-2)

MAXO suggestions: hematopoietic cell transplantation; bone marrow transplantation.

12.3 Emerging/experimental approaches

• Gene therapy/gene editing is discussed as a future curative direction in the literature base but was not captured here as a DADA2-specific human clinical trial in the available ClinicalTrials.gov search results. (cooray2021antitumournecrosisfactor pages 8-11)

13. Prevention

No primary prevention strategies exist for monogenic DADA2 beyond reproductive options; preventive care focuses on secondary/tertiary prevention of strokes and vasculitic complications using TNF inhibition and careful avoidance of contraindicated antiplatelet/anticoagulant regimens in patients at risk for hemorrhagic strokes (as emphasized in review discussion). (wouters2024humanada2deficiency pages 1-3)

14. Other species / natural disease

No naturally occurring veterinary DADA2 analog was identified in retrieved sources.

15. Model organisms

15.1 Key models and why they matter

• Rodents: ADA2 ortholog absent (“present in all mammals except rodents”), limiting classical mouse modeling. (greinertollersrud2024ada2isa pages 1-3, hashem2017deficiencyofadenosine pages 1-2)
• Zebrafish (2024): cecr1b loss-of-function recapitulates vascular and hematopoietic phenotypes; rescues with recombinant human ADA2 and adenosine receptor pathway modulation. (brix2024ada2regulatesinflammation pages 1-2, brix2024ada2regulatesinflammation pages 7-10)
• Porcine tissue: porcine brain ADA2 used for glycan profiling supporting lysosomal targeting. (greinertollersrud2024ada2isa pages 1-3)

15.2 Applications and limitations

Zebrafish enable mechanistic dissection of endothelial inflammation and HSPC emergence defects and provide a platform for testing ADA2 replacement and purinergic pathway modulators; translation to human disease requires validation in patient-derived cells and clinical cohorts given species differences and the complex immune phenotype. (brix2024ada2regulatesinflammation pages 1-2, brix2024ada2regulatesinflammation pages 7-10)

Notes on citation granularity (PMID requirement)

The retrieved full texts in this run primarily provided DOIs and did not include PubMed IDs for most papers, except where OpenTargets lists PMIDs (e.g., 24552284/24552285 as discovery-era links). (OpenTargets Search: Deficiency of adenosine deaminase 2,DADA2-ADA2,CECR1) For a production-grade knowledge base entry, each cited DOI should be cross-walked to PMID in PubMed and recorded. This is a curation step rather than a scientific uncertainty.

URLs and publication dates (selected key sources)

• Wouters et al. 2024-07-06 (online): Human ADA2 Deficiency: Ten Years Later. Current Allergy and Asthma Reports. https://doi.org/10.1007/s11882-024-01163-9 (wouters2024humanada2deficiency pages 1-3)
• Dzhus et al. 2023-08-07 (online): A Narrative Review of the Neurological Manifestations of Human ADA2 Deficiency. Journal of Clinical Immunology. https://doi.org/10.1007/s10875-023-01555-y (dzhus2023anarrativereview pages 1-2)
• Barron et al. 2022-01-10: The Spectrum of DADA2: 60 Patient Cohort. Frontiers in Immunology. https://doi.org/10.3389/fimmu.2021.811473 (barron2022thespectrumof pages 1-2)
• Cooray et al. 2021: Anti-TNF treatment… prevention of ischaemic events… Rheumatology. https://doi.org/10.1093/rheumatology/keaa837 (cooray2021antitumournecrosisfactor pages 1-4)
• Hashem et al. 2021-07-29 (online): HCT cures DADA2: report on 30 patients. Journal of Clinical Immunology. https://doi.org/10.1007/s10875-021-01098-0 (hashem2021hematopoieticcelltransplantation pages 1-2)
• Greiner‑Tollersrud et al. 2024-11-26: ADA2 is a lysosomal deoxyadenosine deaminase… regulating TLR9. Cell Reports. https://doi.org/10.1016/j.celrep.2024.114899 (greinertollersrud2024ada2isa pages 1-3)
• Brix et al. 2024-05: ADA2 regulates inflammation and HSC emergence via A2bR pathway in zebrafish. Communications Biology. https://doi.org/10.1038/s42003-024-06286-3 (brix2024ada2regulatesinflammation pages 1-2)

References

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7. (barron2022thespectrumof pages 4-7): Karyl S. Barron, Ivona Aksentijevich, Natalie T. Deuitch, Deborah L. Stone, Patrycja Hoffmann, Ryan Videgar-Laird, Ariane Soldatos, Jenna Bergerson, Camilo Toro, Cornelia Cudrici, Michele Nehrebecky, Tina Romeo, Anne Jones, Manfred Boehm, Jennifer A. Kanakry, Dimana Dimitrova, Katherine R. Calvo, Hawwa Alao, Devika Kapuria, Gil Ben-Yakov, Dominique C. Pichard, Londa Hathaway, Alessandra Brofferio, Elisa McRae, Natalia Sampaio Moura, Oskar Schnappauf, Sofia Rosenzweig, Theo Heller, Edward W. Cowen, Daniel L. Kastner, and Amanda K. Ombrello. The spectrum of the deficiency of adenosine deaminase 2: an observational analysis of a 60 patient cohort. Frontiers in Immunology, Jan 2022. URL: https://doi.org/10.3389/fimmu.2021.811473, doi:10.3389/fimmu.2021.811473. This article has 96 citations and is from a peer-reviewed journal.

8. (melo2023abraziliannationwide pages 4-6): Adriana Melo, Luciana Martins de Carvalho, Virginia Paes Leme Ferriani, André Cavalcanti, Simone Appenzeller, Valéria Rossato Oliveira, Herberto Chong Neto, Nelson Augusto Rosário, Fabiano de Oliveira Poswar, Matheus Xavier Guimaraes, Cristina Maria Kokron, Rayana Elias Maia, Guilherme Diogo Silva, Gabriel Keller, Mauricio Domingues Ferreira, Dewton Moraes Vasconcelos, Myrthes Anna Maragna Toledo-Barros, Samar Freschi Barros, Nilton Salles Rosa Neto, Marta Helena Krieger, Jorge Kalil, and Leonardo Oliveira Mendonça. A brazilian nationwide multicenter study on deficiency of deaminase-2 (dada2). Advances in Rheumatology, 63:1-9, May 2023. URL: https://doi.org/10.1186/s42358-023-00303-5, doi:10.1186/s42358-023-00303-5. This article has 3 citations.

9. (ashari2023acaseseries pages 1-2): Kosar Asna Ashari, Nahid Aslani, Nima Parvaneh, Raheleh Assari, Morteza Heidari, Mohammadreza Fathi, Fatemeh Tahghighi Sharabian, Alireza Ronagh, Mohammad Shahrooei, Alireza Moafi, Nima Rezaei, and Vahid Ziaee. A case series of ten plus one deficiency of adenosine deaminase 2 (dada2) patients in iran. Pediatric Rheumatology Online Journal, Jun 2023. URL: https://doi.org/10.1186/s12969-023-00838-3, doi:10.1186/s12969-023-00838-3. This article has 7 citations.

10. (barron2022thespectrumof pages 8-10): Karyl S. Barron, Ivona Aksentijevich, Natalie T. Deuitch, Deborah L. Stone, Patrycja Hoffmann, Ryan Videgar-Laird, Ariane Soldatos, Jenna Bergerson, Camilo Toro, Cornelia Cudrici, Michele Nehrebecky, Tina Romeo, Anne Jones, Manfred Boehm, Jennifer A. Kanakry, Dimana Dimitrova, Katherine R. Calvo, Hawwa Alao, Devika Kapuria, Gil Ben-Yakov, Dominique C. Pichard, Londa Hathaway, Alessandra Brofferio, Elisa McRae, Natalia Sampaio Moura, Oskar Schnappauf, Sofia Rosenzweig, Theo Heller, Edward W. Cowen, Daniel L. Kastner, and Amanda K. Ombrello. The spectrum of the deficiency of adenosine deaminase 2: an observational analysis of a 60 patient cohort. Frontiers in Immunology, Jan 2022. URL: https://doi.org/10.3389/fimmu.2021.811473, doi:10.3389/fimmu.2021.811473. This article has 96 citations and is from a peer-reviewed journal.

11. (barron2022thespectrumof pages 1-2): Karyl S. Barron, Ivona Aksentijevich, Natalie T. Deuitch, Deborah L. Stone, Patrycja Hoffmann, Ryan Videgar-Laird, Ariane Soldatos, Jenna Bergerson, Camilo Toro, Cornelia Cudrici, Michele Nehrebecky, Tina Romeo, Anne Jones, Manfred Boehm, Jennifer A. Kanakry, Dimana Dimitrova, Katherine R. Calvo, Hawwa Alao, Devika Kapuria, Gil Ben-Yakov, Dominique C. Pichard, Londa Hathaway, Alessandra Brofferio, Elisa McRae, Natalia Sampaio Moura, Oskar Schnappauf, Sofia Rosenzweig, Theo Heller, Edward W. Cowen, Daniel L. Kastner, and Amanda K. Ombrello. The spectrum of the deficiency of adenosine deaminase 2: an observational analysis of a 60 patient cohort. Frontiers in Immunology, Jan 2022. URL: https://doi.org/10.3389/fimmu.2021.811473, doi:10.3389/fimmu.2021.811473. This article has 96 citations and is from a peer-reviewed journal.

12. (OpenTargets Search: Deficiency of adenosine deaminase 2,DADA2-ADA2,CECR1): Open Targets Query (Deficiency of adenosine deaminase 2,DADA2-ADA2,CECR1, 2 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.

13. (melo2023abraziliannationwide pages 1-2): Adriana Melo, Luciana Martins de Carvalho, Virginia Paes Leme Ferriani, André Cavalcanti, Simone Appenzeller, Valéria Rossato Oliveira, Herberto Chong Neto, Nelson Augusto Rosário, Fabiano de Oliveira Poswar, Matheus Xavier Guimaraes, Cristina Maria Kokron, Rayana Elias Maia, Guilherme Diogo Silva, Gabriel Keller, Mauricio Domingues Ferreira, Dewton Moraes Vasconcelos, Myrthes Anna Maragna Toledo-Barros, Samar Freschi Barros, Nilton Salles Rosa Neto, Marta Helena Krieger, Jorge Kalil, and Leonardo Oliveira Mendonça. A brazilian nationwide multicenter study on deficiency of deaminase-2 (dada2). Advances in Rheumatology, 63:1-9, May 2023. URL: https://doi.org/10.1186/s42358-023-00303-5, doi:10.1186/s42358-023-00303-5. This article has 3 citations.

14. (brix2024ada2regulatesinflammation pages 1-2): Alessia Brix, Laura Belleri, Alex Pezzotta, Emanuela Pettinato, Mara Mazzola, Matteo Zoccolillo, Anna Marozzi, Rui Monteiro, Filippo Del Bene, Alessandra Mortellaro, and Anna Pistocchi. Ada2 regulates inflammation and hematopoietic stem cell emergence via the a2br pathway in zebrafish. Communications Biology, May 2024. URL: https://doi.org/10.1038/s42003-024-06286-3, doi:10.1038/s42003-024-06286-3. This article has 10 citations and is from a peer-reviewed journal.

15. (wouters2024humanada2deficiency pages 3-4): Marjon Wouters, Lisa Ehlers, Mariia Dzhus, Verena Kienapfel, Giorgia Bucciol, Selket Delafontaine, Anneleen Hombrouck, Bethany Pillay, Leen Moens, and Isabelle Meyts. Human ada2 deficiency: ten years later. Current Allergy and Asthma Reports, 24:477-484, Jul 2024. URL: https://doi.org/10.1007/s11882-024-01163-9, doi:10.1007/s11882-024-01163-9. This article has 17 citations and is from a peer-reviewed journal.

16. (wouters2024humanada2deficiency pages 4-5): Marjon Wouters, Lisa Ehlers, Mariia Dzhus, Verena Kienapfel, Giorgia Bucciol, Selket Delafontaine, Anneleen Hombrouck, Bethany Pillay, Leen Moens, and Isabelle Meyts. Human ada2 deficiency: ten years later. Current Allergy and Asthma Reports, 24:477-484, Jul 2024. URL: https://doi.org/10.1007/s11882-024-01163-9, doi:10.1007/s11882-024-01163-9. This article has 17 citations and is from a peer-reviewed journal.

17. (cooray2021antitumournecrosisfactor pages 8-11): Samantha Cooray, Ebun Omyinmi, Ying Hong, Charalampia Papadopoulou, Lorraine Harper, Eslam Al-Abadi, Ruchika Goel, Shirish Dubey, Mark Wood, Stephen Jolles, Stefan Berg, Maria Ekelund, Kate Armon, Despina Eleftheriou, and Paul A Brogan. Anti-tumour necrosis factor treatment for the prevention of ischaemic events in patients with deficiency of adenosine deaminase 2 (dada2). Rheumatology, 60:4373-4378, Jan 2021. URL: https://doi.org/10.1093/rheumatology/keaa837, doi:10.1093/rheumatology/keaa837. This article has 74 citations and is from a peer-reviewed journal.

18. (hashem2017deficiencyofadenosine pages 1-2): Hasan Hashem, Susan J Kelly, Nancy J Ganson, and Michael S Hershfield. Deficiency of adenosine deaminase 2 (dada2), an inherited cause of polyarteritis nodosa and a mimic of other systemic rheumatologic disorders. Current Rheumatology Reports, 19:1-9, Oct 2017. URL: https://doi.org/10.1007/s11926-017-0699-8, doi:10.1007/s11926-017-0699-8. This article has 84 citations and is from a peer-reviewed journal.

19. (brix2024ada2regulatesinflammation pages 7-10): Alessia Brix, Laura Belleri, Alex Pezzotta, Emanuela Pettinato, Mara Mazzola, Matteo Zoccolillo, Anna Marozzi, Rui Monteiro, Filippo Del Bene, Alessandra Mortellaro, and Anna Pistocchi. Ada2 regulates inflammation and hematopoietic stem cell emergence via the a2br pathway in zebrafish. Communications Biology, May 2024. URL: https://doi.org/10.1038/s42003-024-06286-3, doi:10.1038/s42003-024-06286-3. This article has 10 citations and is from a peer-reviewed journal.

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