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.
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.
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.
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.
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).