A new CECR1 mutation associated with severe hematological involvement in ADA2 deficiency

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Abstract Background: The deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessively inherited disease resulting from loss-of-function mutations in ADA2, formerly named CECR1 (cat eye syndrome chromosome region, candidate 1) gene. Disease manifestations could be separated into three major phenotypes: inflammatory/vascular, immune dysregulatory and hematologic, however, most patients presented with significant overlap between these three phenotype groups. Due to its large heterogeneity, DADA2 is often mistaken with other connective tissue diseases. Over 60 DADA2-associated mutations have been identified so far, still we describe a new mutation with possible relation to severe hematological involvement Case presentation: We present a case of DADA2 deficiency with disease onset at 3 years old with fever, oligoarthritis, mouth sores and recurrent episodes of neutropenia misdiagnosed as Behcet disease, then systemic lupus erythematosus. At the age of 18 she developed gastrointestinal vasculitis complicated with multiple bowel resections, enterocutaneous fistulas and lower limb ischemia. Genetic testing reveals heterozygous mutations at positions 139 (exon 2) and 661_664 (exon 4) of the coding sequence of ADA2 (c.139G>A, c.661_664del), resulting respectively in amino acid substitution p.Gly47Arg and premature translational stop signal p.Ala221Glnfs*45 in ADA2. Thus, the patient was diagnosed with ADA2 deficiency. TNF blockers were started but the patient died due to septic complications related to severe, nonresponsive pancytopenia. Conclusions: Our case highlights the valuable diagnostic benefit of early specific genetic testing for patients with complex unclear diseases in which vasculopathy/vasculitis, dysregulated immune function and/or hematologic abnormalities may predominate.

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