Diagnosis and management of adenosine deaminase 2 deficiency children: the experience from China

Wei Wang,Tiannan Zhang,Hongmei Song,Wenjie Zheng,Qian Liu,Ji Li,Yanqing Dong,Lin Wang,Linqing Zhong

doi:10.1186/s12969-021-00535-z

Abstract

BackgroundDeficiency of adenosine deaminase 2 (DADA2) is a rare autoinflammatory disease caused by mutations in the ADA2 gene. Few Chinese cases have been reported. We describe and compare the clinical features, genotypes, and treatments of Chinese DADA2 patients and non-Chinese patients.MethodsPrimary immunodeficiency disease panel or whole-exome sequencing was performed for suspected cases, and assays for adenosine deaminase 2 (ADA2) enzyme activity were also carried out for the patients and their parents. Case reports of Chinese and non-Chinese patients with DADA2 were searched in PubMed and Chinese national databases.ResultsSeven unrelated children from China with DADA2 were included in our study. Five were identified at Peking Union Medical College Hospital, and two had been reported previously (1 on PubMed and 1 in Chinese literature). Fourteen mutations in ADA2 were identified, 7 of which have not previously been reported in non-Chinese patients. Four children who underwent enzymatic analysis had lower ADA2 activity compared with their parents. Phenotypic manifestations included fever, skin symptoms, vasculitis, and neurologic involvement. Treatments varying from steroids, immunosuppressants, and tocilizumab, anti-TNF therapy and hematopoietic stem cell transplantation (HSCT) were effective depending on phenotype and severity.ConclusionThis study includes the largest number of Chinese DADA2 patients to date. We recommend the combination of enzymatic analysis with gene screening to confirm the diagnosis. Different genotypes were observed among Chinese DADA2 patients; most phenotypes were similar to those of non-Chinese DADA2 patients, except for growth retardation. Disease remission might not be achieved with anti-IL-6 therapy.

Highlights

Deficiency of adenosine deaminase 2 (DADA2) is a rare autoinflammatory disease caused by mutations in the ADA2 gene
Five of them were diagnosed with DADA2 followed in the Department of Pediatrics, Peking Union Medical College Hospital (PUMCH), one of whom was reported in the Chinese literature in October 2018
Only one heterozygous variation was initially found in P2, his decreasing activity of ADA2 indicated that he had DADA2

Summary

Introduction

Deficiency of adenosine deaminase 2 (DADA2) is a rare autoinflammatory disease caused by mutations in the ADA2 gene. Deficiency of adenosine deaminase 2 (DADA2) is a rare, autosomal recessive autoinflammatory disease that is caused by mutations in the ADA2 gene [1]. DADA2 is usually a childhood-onset disease, with 24% of cases reported before 1 year of age, and 77% before the age of 10. DADA2 was first described in 2014 [1, 2], and more than 300 cases have been reported in the literature far [3,4,5,6,7]. Several reports have suggested that DADA2 may cause broad-spectrum manifestations, including early-onset stroke, nodular vasculitis, immunodeficiency, red-cell aplasia, and neutropenia. Some reports have shown no evidence for vasculitis in patients with DADA2 [8], with hematologic involvement or lymphoproliferation possibly being the only manifestation [9]

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Results

Discussion

Conclusion