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ADA2 deficiency (DADA2)

Hypogammaglobulinémie DADA2
Scanner cerebral AVC, DADA2
Livedo pied DADA2


  • Very rare disease.

  • Autoinflammatory disease.

  • Genetic disease, autosomal recessive linked to mutations of the ADA2 gene (formerly called CECR1).


•     Its prevalence is unknown, it is estimated that there are around thirty cases in France in 2022 and >300 people affected worldwide.
•     It affects both men and women.
•     It typically begins during the first decade of life.
•     It affects all populations of the world.


ADA2 deficiency (DADA2) is an autosomal recessive disease linked to mutations in the ADA2 gene, so you must have two mutations to be sick. It particularly affects children from consanguineous marriages, those whose parents are related, and several members of the same siblings can be affected.


Since childhood, patients present with recurrent bouts of fever of variable duration and frequency associated with the following signs in decreasing order of frequency:

  • Eruptions on the skin: livedo (like the stitches of a purplish net), ulcers, leg knots, finger necrosis, mouth ulcers.

  • Cerebrovascular accidents.

  • Intense abdominal pain, which may mimic a surgical abdomen.

  • Muscle and/or joint pain in large joints (ankles, knees).

  • Repeated infections due to diminished immune defenses.

  • An enlargement of the liver and spleen.

  • More rarely a deep anemia.

  • More rarely psychiatric disorders.

  • The picture may be that of polyarteritis nodosa.


Early diagnosis is essential to ensure proper management.
The diagnosis is clinical, biological and genetic.

Blood samples will look for an inflammatory syndrome (elevation of C-reactive protein) which may be present only during crises. A decrease in blood ADA2 can be sought in France or in the United States. A genetic analysis in search of mutation of the ADA2 gene can be carried out in several French genetic laboratories.


The main complication is related to sequelae induced by cerebrovascular accidents if they induce paralysis of a limb or one side of the body. The appearance of AA amyloidosis must be monitored during DADA2 but it is very rare (<3 cases reported worldwide, i.e. <1% of DADA2 cases).


The treatment of the crisis is based on antipyretics in case of fever such as paracetamol and analgesics in case of pain such as NSAIDs.

The objective of background treatment is to normalize CRP and prevent the onset of cerebrovascular accidents. It may be the subject of an opinion from an expert reference center in order to take into account each case in its specificity, according to age, impact, possible complications of the disease. It will be adapted according to the clinical form and the impact of the disease. 

An anti-TNFa biotherapy by Etanercept (EMBREL®) has demonstrated its effectiveness in normalizing inflammation and preventing the recurrence of strokes.

In some cases with serious haematological involvement, a bone marrow transplant may be discussed.

In some very mild cases with simple skin involvement, treatment is discussed with disease experts.

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