Deficiency of adenosine deaminase type 2 (DADA2): A description of phenotype and genotype in 15 cases

Sira Nanthapisal, Claire Murphy, Ebun Omoyinmi, Ying Hong, Ariane Standing, Stefan Berg, Maria Ekelund, Stephen Jolles, Lorraine Harper, Taryn Youngstein, Kimberly Gilmour, Nigel Klein, Despina Eleftheriou, Paul A Brogan

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OBJECTIVES: To describe the clinical features, genotype, and treatment of a series of subjects with confirmed Deficiency of Adenosine Deaminase 2 (DADA2) referred to Great Ormond Street Hospital NHS Foundation Trust (GOSH), London. Methods All symptomatic subjects were referred for genetic testing for suspected DADA2; relatives of index cases were also screened. The demographic, clinical, laboratory characteristics and treatments were recorded. Genetic analyses performed included whole-exome sequencing in 4 patients; and Sanger sequencing of Cat Eye Syndrome Chromosome Region Candidate 1 (CECR1) in all subjects. ADA2 enzyme activity assay, and quantitative PCR of CECR1 mRNA were also performed. Results We identified 15 subjects with DADA2; 5 subjects were asymptomatic (relatives of index cases; age 5-42 years). Homozygous or compound heterozygous mutations in CECR1 were identified in all subjects. The phenotypic manifestations of the symptomatic DADA2 patients included livedo racemosa (73.3%); neurologic involvement (53.3%); and immune deficiency (46.6%). CECR1 mRNA expression in 8 subjects, including five pre-symptomatic subjects was significantly lower than healthy controls (p=0.0016). DADA2 subjects (with or without symptoms) also had lower ADA2 enzyme activity compared to healthy paediatric controls (p<0.0001), and sporadic cases of childhood polyarteritis nodosa without CECR1 mutation (p=0.0108). Nine/10 symptomatic patients required anti-TNF-α therapy. Conclusion The clinical severity of DADA2 ranged from limited cutaneous to severe multi-systemic vasculitis; one third (5/15) of our cases were currently asymptomatic, and required close monitoring. We recommend CECR1 screening for: unaffected siblings of index cases; cases of familial vasculitis; and patients with polyarteritis nodosa recalcitrant to standard treatment. This article is protected by copyright. All rights reserved.

Original languageEnglish
JournalArthritis & Rheumatology (Hoboken)
Early online date5 Apr 2016
Publication statusE-pub ahead of print - 5 Apr 2016


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