Deficiency of Adenosine Deaminase 2 (DADA2) – aka Fever with Early Onset Stroke (FEOS)

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Acronym:
DADA2

SAID group:
ADA2 deficiency

Gene:
ADA2 (aka CECR1)

Inheritance:
Autosomal recessive.

Ethnicity:
Unknown.

Frequency:
Unknown but rare.

Timing of symptoms:
Intermittent, recurrent fevers, livedo reticularis rash, vasculopathy, and a high risk for early-onset lacunar stroke. [73] [74]

Age of onset:
Onset of symptoms in infancy–early childhood with recurrent fevers, livedo reticularis rash, and vasculopathy. [73] [74]

Skin cutaneous:
Livedo reticularis rash is common. A few with polyarteritis nodosa (PAN). Diffuse vasculopathy, with impaired endothelial integrity and endothelial cellular activation. [73] [74] Predominant levels of neutrophils and macrophages in the interstitium; perivascular T lymphocytes, without obvious vasculitis. [131]

Neurologic:
Recurrent fevers, and early-onset lacunar strokes is common. Some patients do not have strokes. [131] Possible adult stroke risk. Brain biopsies: diffuse vasculopathy, with impaired endothelial integrity and endothelial cellular activation. [73] [74] The first stroke often occurs before 5 years of age. [131]

Auditory:
Unknown. [73] [74]

Ophthalamic:
Unknown.[73] [74] Strokes have the potential to cause blindness.

Cardiopulmonary:
Unknown. [73] [74]

Abdominal:
Hepatosplenomegaly; diffuse vasculopathy noted in the liver. [73] [74] Portal hypertension in some patients. [131]

Lymphatic:
Not noted. [73] [74]

Joints bones muscles cartilage:
Not noted. [73] [74]

Vasculitis:
Diffuse vasculopathy in the skin, liver and brain. [73] [74] No signs of cerebral vasculitis noted. One case of necrotizing vasculitis [131]

Amyloidosis:
Not noted. [73] [74]

Abnormal labs:
High: CRP, ESR with flares. Cytopenia. Blood: 10-fold decrease in ADA2. Low: IgM [131], ADA2-specific adenosine deaminase activity: blood & CD14+ monocytes. [73] [74] Absence of hypercoagulability. [131] Negative for antiphospholipid antibodies (APLAs). Some patients later develop a positive lupus anticoagulant (LA) level. Some have mild immunodeficiency.

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