Disrupted N-linked Glycosylation As a Disease Mechanism in Deficiency of ADA2.

Deficiency of adenosine deaminase 2 (DADA2) causes systemic inflammation, immunodeficiency, vasculitis, and early-onset strokes.1,2 This variable phenotype is caused by recessively inherited loss-of-function mutations of CECR1 (cat eye syndrome chromosome region 1), which encodes adenosine deaminase 2 (ADA2). At least 30 pathogenic mutations in the CECR1 gene have described in more than 125 patients.3,4 Although absent plasma ADA2 activity is a hallmark of the disease, how individual mutations affect ADA2 expression and function has been largely unexplored.