| Category | Item | Summary | Key quantitative details | Citation placeholders |
|---|---|---|---|---|
| Disease identifiers | Preferred name | Deficiency of adenosine deaminase 2; commonly abbreviated **DADA2** | First described in 2014; complex systemic autoinflammatory/inborn error of immunity phenotype | [CITATION] |
| Disease identifiers | Standard identifiers | **MONDO:** MONDO_0014306; **OMIM:** 615688 | OpenTargets links MONDO_0014306 to ADA2 as the associated target | [CITATION] |
| Disease identifiers | Common synonyms | Human ADA2 deficiency; ADA2 deficiency; CECR1 deficiency; deficiency of adenosine deaminase type 2 | ADA2 was formerly named **CECR1** | [CITATION] |
| Genetics / inheritance | Causal gene | **ADA2** (formerly **CECR1**) encodes adenosine deaminase 2 | Biallelic deleterious/loss-of-function variants cause disease | [CITATION] |
| Genetics / inheritance | Inheritance | **Autosomal recessive** | Homozygous or compound heterozygous pathogenic variants reported | [CITATION] |
| Genetics / inheritance | Variant spectrum | Most reported variants are missense, but splice/intronic/structural variants also occur | 2024 review notes **>400 cases** reported overall | [CITATION] |
| Phenotype domains | Major domains | Three overlapping domains: **inflammatory/vascular**, **immune dysregulatory**, **hematologic** | Most patients show overlap rather than a single isolated phenotype | [CITATION] |
| Phenotype domains | Inflammatory / vascular | Cutaneous manifestations, livedo racemosa/reticularis, PAN-like vasculopathy, stroke, end-organ vasculitis | In Barron 2022, cardinal features were **cutaneous manifestations and stroke** | [CITATION] |
| Phenotype domains | Immune dysregulatory | Hypogammaglobulinemia, low/absent class-switched memory B cells, poor vaccine responses | Barron 2022 notes immune dysregulation was common, but infectious complications were **exceedingly rare** in that cohort | [CITATION] |
| Phenotype domains | Hematologic | PRCA, immune-mediated neutropenia, thrombocytopenia, pancytopenia, bone marrow failure | Barron 2022: hematologic findings were seen in **~50%** of patients | [CITATION] |
| Neurologic burden | Any neurological event | Neurologic involvement is a major disease burden and can be initial or sole presentation | Dzhus 2023 review: **50.3%** had ≥1 neurological event; initial manifestation in **5.7%**; sole manifestation in **0.6%** | [CITATION] |
| Neurologic burden | Cerebrovascular events | Stroke is the dominant neurologic manifestation | Among patients with neurologic manifestations, **77.5%** had ≥1 cerebrovascular accident; **35.9%** had multiple stroke episodes | [CITATION] |
| Neurologic burden | Stroke localization | Lacunar ischemic strokes predominate, with characteristic anatomic distribution | Brainstem involvement **37.3%** and deep gray matter involvement **41.6%** of ischemic strokes in the review | [CITATION] |
| Age / onset | Typical onset | Usually childhood onset, but adult-onset cases occur | Mean age of onset in reviewed neurologic literature was **~7 years**; 2023 review notes onset often by age 10 | [CITATION] |
| Population statistics | Prevalence estimate | Rare disease; likely underrecognized | 2024 review estimated prevalence at **~1:222,000** and carrier frequency **~1:236** using residual activity modeling | [CITATION] |
| Diagnostics | Enzyme activity testing | Low or absent **plasma/serum ADA2 enzymatic activity** is a core diagnostic modality | Functional testing is especially useful when variants are uncertain or urgent diagnosis is needed | [CITATION] |
| Diagnostics | Molecular diagnosis | Confirm by **biallelic pathogenic ADA2 variants** via single-gene testing, panel, WES/WGS as appropriate | Diagnosis can also require follow-up for splice, intronic, or structural variants | [CITATION] |
| Diagnostics | Practical diagnostic statement | Current reviews recommend combining genetics with enzyme activity | Identification of biallelic variants **plus severely diminished/absent ADA2 activity** is considered diagnostic | [CITATION] |
| Treatment | Anti-TNF agents | First-line disease-modifying therapy for vasculitic/ischemic phenotype; not reliably effective for marrow failure/immunodeficiency | Includes etanercept, infliximab, adalimumab in published series | [CITATION] |
| Treatment outcomes | Anti-TNF effectiveness (multicenter) | Major reduction in ischemic events after anti-TNF treatment | Cooray 2021: median ischemic event rate fell from **2.37 per 100 patient-months** pre-treatment to **0.00 per 100 patient-months** post-treatment (**p<0.0001**); PVAS fell from **20/63** to **2/63** | [CITATION] |
| Treatment outcomes | Anti-TNF effectiveness (NIH cohort) | Sustained stroke prevention signal in longitudinal cohort | Barron 2022: **no strokes** observed during **2026–2027 patient-months** on TNF inhibitors | [CITATION] |
| Treatment limitations | Anti-TNF nonresponse domains | Hematologic failure and severe immunodeficiency often persist despite TNF blockade | Cooray 2021 and other cohorts report these phenotypes may require transplantation | [CITATION] |
| Curative therapy | Allogeneic HCT / HSCT | Considered definitive/curative especially for bone marrow failure, severe cytopenia, severe immunodeficiency | Reverses hematologic, immunologic, and vascular disease in many reported patients | [CITATION] |
| Curative therapy outcomes | International HCT cohort | Strong survival and biochemical correction after transplantation | Hashem 2021: **30 patients**, **38 HCTs**, median age **9 years**; **2-year OS 97%**; **2-year GvHD-free relapse-free survival 73%**; ADA2 activity normalized in **16/17** tested; **6** patients required >1 HCT | [CITATION] |
| Real-world implementation | Cohort examples | National and multicenter cohorts confirm pediatric predominance and anti-TNF responsiveness for vasculopathy | Brazil 2023: **18 patients**, pediatric onset median **5 years**, anti-TNF responses favorable; Iran 2023: **11 patients**, strokes in **64%**, anti-TNF response in **8** treated patients | [CITATION] |


*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.*