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

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Abstract

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.

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Data availability

The datasets generated during and analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgments

We thank the support from the patient and all his family. We thank all the doctors and physicians who had helped and taken care of the patient.

Funding

This work was funded by the Natural Science Foundation of Beijing (Grant No. 7192170), the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS) (Grant No. 2017-I2M-3-001, 2016-I2M-1-002), the National Natural Science Foundation of China (NSFC) (Grant No. 81788101), the National Key Research and Development Program of China (Grant No. 2016YFC0901500; 2016YFC0901501), Capital Medical Development Research Fund (2018-1-4012), the Clinical and Translational Medical Research Fund of Chinese Academy of Medical Sciences (No. 2019XK320013), the Fundamental Research Funds for the Central Universities (Grant No. APL20100310010301019), the CAMS Initiative for Innovative Medicine (2016-I2M-1-008), and the Capital Health Research and Development of Special (2016-2-40114).

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Correspondence to Min Shen, Rongrong Wang or Xuejun Zeng.

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This study was approved by the Institutional Review Board of Peking Union Medical College Hospital and performed according to the Declaration of Helsinki. Informed consent was obtained from the patient and his family.

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Zhang, B., Sun, Y., Xu, N. et al. Adult-onset deficiency of adenosine deaminase 2—a case report and literature review. Clin Rheumatol 40, 4325–4339 (2021). https://doi.org/10.1007/s10067-021-05587-w

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