[MIM 615 688]

(ADA2 deficiency, DADA2)

Not to be confused with Severe combined immunodeficiency due to adenosine deaminase deficiency (see this term).

Prevalence estimated at 1/222,000. Monogenic autoinflammatory disease caused by the autosomal recessive transmission of a loss-of-function mutation in the ADA2 (or CECR1) gene (22q11.2.). This loss-of-function leads to an increase in the population of proinflammatory M1 macrophages and to increased cytokine production.

Clinical presentation is highly variable:

-        mean age of onset: 92 months (sd 108)

-        skin involvement (67.9 %): livedo, ulcers, leg erythema nodosum, vasculitis with finger necrosis, mouth ulcers. The clinical presentation may   similar to periarteritis nodosa.

-        neurological involvement: stroke, polyneuropathy (51 %)

-        recurrent fever (51.3 %)

-        intense abdominal pain, mimicking a surgical abdomen.

-        muscle pain and arthralgia (ankles, knees) (35.4 %).

-        recurrent infections (18.5 %) due to humoral immunity deficiency (42.3 %): low IgG levels, B lymphocyte deficiency

-        hepatosplenomegaly

-        hematological involvement (56.3 %): anemia (sometimes profound), leukopenia, pancytopenia

-        more rarely, psychiatric disorders.

Some authors distinguish 4 phenotypes: inflammatory/vascular; hematological; immunodeficient; presymptomatic (discovered by family screening).

Diagnosis: low blood deaminase levels.

In case of crisis, treatment is based on antipyretics for fever, such as paracetamol, and analgesics for pain, such as NSAIDs.

Background treatment aims to normalize CRP and prevent strokes.

In the case of inflammatory/cutaneous involvement, anti-TNFa biotherapy (etanercept and adalimunab) has proven effective in normalizing inflammation, preventing skin damage and stroke recurrence.

In the event of severe hematological involvement, stem cell transplantation should be considered.

 Anesthetic implications: 

fragile skin and mucous membranes, antibiotic prophylaxis and asepsis measures; side effects of the immunosuppressive therapy.

References : 

-        Lee PY, Davidson BA, Abraham RS, Alter B, Arostegui JI, Bell K, MFA; Belot A, Bergerson JRE et al, for the DADA2 Foundation.
Evaluation and management of Deficiency of Adenosine Deaminase 2 : an international consensus statement.
JAMA Network Open. 2023; 6 :e2315894.

-        Maccora I, Maniscalco V, Campani S, Carrera S, Abbati G, Marrani E, Mastrolia MV, Simonini G.
A wide spectrum of phenotype of deficiency of deaminase 2 (DADA2): a systematic literature review.
Orphanet Journal of Rare Diseases 2023 ; 18:117 https://doi.org/10.1186/s13023-023-02721-6

Updated June 2023