Abstract
Objective
To describe the clinical features, genotype, and treatment approaches of patients with confirmed adenosine deaminase 2 (ADA2) deficiency with dissimilar phenotypes.
Methods
A case series of five DADA2 patients from three families was presented. The clinical and laboratory data, treatment protocols, and outcome of the patients were recorded from the patients’ medical charts. ADA2 gene was screened by next generation sequencing first and then verified by Sanger sequencing. Serum ADA2 enzyme activity was measured by modified spectrophotometric method.
Results
The median (min–max) age at onset of symptoms and age at diagnosis were 11 (9–13.8) years and 15 (9–19) years, respectively. The median (min–max) follow-up period was 8 (6–45) months. There was consanguinity in two families (2/3). The main clinical manifestations are musculoskeletal (5/5), dermatological (4/5), and neurological (2/5). Homozygosity for the p.G47R mutation in ADA2 gene was detected in three patients. A homozygous mutation in ADA2 gene (c.650 T > A; p.Val217Asp) was detected in two siblings. Plasma ADA2 enzymatic activity was absent in all patients. Anti-tumor necrosis factor (TNF) therapy was commenced, and all patients became clinically inactive with normal acute-phase reactants.
Conclusion
ADA2 mutations should be checked in patients with presence of inflammation and livedoid vasculitis when they have neurological findings, especially in the form of stroke; and a history suggesting for an inherited disease; or presence of resistance to conventional treatment. Besides, anti-TNF seems to be useful for treatment of DADA2.
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Acknowledgments
We would like to acknowledge Professor Dr. Michael Hershfield for evaluating the plasma level of adenosine deaminase 2 activity in the patients, interpreting the data, and critically reviewing the manuscript for important intellectual content.
Authors’ Contributions
Drs. Tanatar and Aktay Ayaz provided clinical care for the patients, contributed to writing the initial draft and revised the manuscript; Karadağ and Çakan provided clinical care for the patients, Dr. Sönmez interpreted data; Drs. Sözeri and Demirkol performed a genetic analysis of the patient; and all authors contributed to writing and revising the initial draft. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
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Tanatar, A., Karadağ, Ş.G., Sözeri, B. et al. ADA2 Deficiency: Case Series of Five Patients with Varying Phenotypes. J Clin Immunol 40, 253–258 (2020). https://doi.org/10.1007/s10875-019-00734-0
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DOI: https://doi.org/10.1007/s10875-019-00734-0