Mutations in ADA2 are associated with a vasculopathy with early-onset stroke and other ischemic injury.
Gene: ADA2 = adenosine deaminase 2
Synonym: CECR1 (cat eye syndrome chromosome region, candidate 1)
Location: 22q11.2
Inheritance: autosomal recessive (often as compound heterozygous mutations)
Mechanism: reduced levels of ADA2 enzyme activity result in compromised endothelial integrity and a vasculitis (ADA2 deficiency = DADA2)
Clinical features of vasculopathy:
(1) neurovascular injury with onset during childhood (lacunar infarcts involving brain stem, deep brain nuclei, subcortical region)
(2) recurrent fever
(3) skin rash (livedo racemosa)
(4) hepatosplenomegaly
(5) systemic vasculitis resembling polyarteritis nodosa or small vessel vasculitis
(6) mild immunodeficiency associated with hypogammaglobulinemia (low serum IgM)
(7) ophthalmologic involvement (retinal artery occlusion, optic nerve atrophy, cranial nerve palsy, etc)
Laboratory findings:
(1) variable neutropenia
(2) variable lupus anticoagulant
(3) variable antinuclear antibody (ANA)
(4) reduced levels of active ADA2 in plasma (measured in ng/mL)
