The coding exons of ADA2 were sequenced in 60 children and adolescents with a diagnosis of PAN, cutaneous PAN, or unclassifiable vasculitis (UCV), any chronic vasculitis with onset at age 5 years or younger, or history of stroke.
Human adenosine deaminase type 2 deficiency (DADA2), due to biallelic deleterious mutations in the ADA2 gene, is the first described monogenic type of small- and medium-size vessel vasculitis.
Reduction of adenosine deaminase 2 (ADA2) activity due to autosomal-recessive loss-of-function mutations in the <i>ADA2</i> gene (previously known as <i>CECR1</i>) results in a systemic vasculitis known as deficiency of ADA2 (DADA2).
Until the diagnosis of DADA2 was confirmed, five patients have been followed-up with the diagnosis of PAN: two patients both with PAN and FMF, and one patient with CAPS and vasculitis.
Deficiency of adenosine deaminase 2 (ADA2) due to homozygous or compound heterozygous mutations in the cat eye syndrome chromosome region, candidate 1 (<i>CECR1</i>) gene causes an autoimmune phenotype with systemic vasculitis affecting the skin, inner organs, and the central nervous system.
In childhood, beside inflammation lanced by ischemia itself, the event of ischemia might be provoked by an underlying inflammatory pathophysiology: transient focal arteriopathy, dissection, sickle cell anemia, Moyamoya and more generalized in meningitides, generalized vasculitis or genetic arteriopathies (as in ADA2).
These associations include ERAP1, CCR1-CCR3, STAT4, KLRC4, GIMAP4, and TNFAIP3 in Behçet's disease; BLK and CD40 in Kawasaki disease; SERPINA1 and SEMA6A in antineutrophil cytoplasmic antibody associated vasculitides; IL12B and FCGR2A/ FCGR2A in Takayasu arteritis; and CECR1 in a newly defined vascular inflammatory syndrome associated with adenosine deaminase (ADA2) deficiency.
Loss-of-function mutations in CECR1 were associated with a spectrum of vascular and inflammatory phenotypes, ranging from early-onset recurrent stroke to systemic vasculopathy or vasculitis.