Adult-onset deficiency of adenosine deaminase 2-a case report and literature review.

Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive disease caused by ADA2 gene mutation that is characterized by three phenotype domains: vasculopathy and inflammation, hematological abnormality, and immunodeficiency. Most patients are pediatric patients; adult-onset patients are only occasionally reported. To describe a Chinese case of adult-onset DADA2 in a Chinese patient and explore the genotype and phenotype characteristics of adult-onset DADA2. We examined the clinical, serological, and genetic features of a Chinese adult-onset DADA2 patient. English literature on DADA2 was reviewed. The clinical and genetic characteristics of different age and mutation subgroups were compared. A Chinese Han male presented with recurrent fever, rash, immunodeficiency, and significant vascular events since the age of 25 years. Serum ADA2 activity was diminished, and genotyping revealed a unique compound heterozygous mutation of exon2-10del/exon7del in the ADA2 gene leading to complete exon 7 deletion. Treatment with a TNFα inhibitor achieved disease control. A total of 269 cases carrying 102 mutations were analyzed through a literature review. Adult-onset patients had few symptoms in all three clinical domains; vasculopathy and inflammation were the major symptoms. Patients with null mutations had early disease onset and more frequent hematological abnormalities and immunodeficiency. Patients in all subgroups responded well to TNFα inhibitors. We reported the first Chinese adult-onset DADA2 patient, with a unique mutation. Screening for and differentiation of DADA2 are recommended for patients of all ages, as they might become symptomatic later in life and treatment strategies differ from those of traditional vasculitis. Key Points • We report a novel compound heterozygous deletion mutations of exons 2-10 and exon 7, leading to complete loss of exon 7 in the ADA2 gene. • Adult-onset DADA2 patients had high similarity to systemic vasculitis. • Null mutations contribute to earlier disease onset and more aggressive disease. • We suggest screening for DADA2 in patients with significant central vasculitis, hematological abnormality and immunodeficiency.