A cohort study on deficiency of ADA2 from China

Abstract

Purpose: Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive autoinflammatory disorder caused by biallelic loss-of-function mutations in ADA2, characterized by systemic inflammation, vasculitis, immunodeficiency, and/or hematologic abnormalities. Methods: A retrospective analysis of patients with DADA2 diagnosed by whole exome sequencing at 17 rheumatology centers across China was conducted. Clinical characteristics, laboratory findings, genotype and treatment responses were analyzed.Results Thirty patients with DADA2 were enrolled in this cohort between January 2015 and December 2021. Median age at onset was 4.3 years and the median age at diagnosis was 7.8 years. All but one patient presented during childhood and two subjects in the cohort died from DADA2-related complications. The patients presented with systemic inflammation (92.9%), vasculitis (86.7%), and hypogammaglobinemia (73.3%) while one patient with pure red cell aplasia (PRCA) and bone marrow failure (BMF) with variable cytopenia was observed in our cohort. Twenty-three (76.7%) patients received TNF inhibitors and all achieved clinical remission. Homozygous variants and compound heterozygous variants were identified in 5 and 25 patients, respective. Two patients received hematopoietic stem cell transplantation (HSCT), and both got remission. Among 39 unique variants in our cohort, six is novel.Conclusion: In order to establish the diagnosis early and prevent devastating clinical outcomes, genetic screening and/ or testing of adenosine deaminase enzymatic activity should be performed in patients with suspected clinical features. TNF inhibitors can be first line drug for patients with vasculitic DADA2. HSCT is an alternative choice for patients with refractory to TNF inhibitors or hematological disorders.

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