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Clinical, imaging and genotypical features of three deceased and five surviving cases with ADA2 deficiency

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Abstract

Deficiency of adenosine deaminase type 2 (DADA2) is a rare form of autoinflammatory disorder with limited reported cases. In this paper, we have presented the clinico-immunological, radiological and genetic characteristics of five surviving and three deceased childhood-onset DADA2 patients. We aimed to compare surviving and deceased patients in terms of clinical features and treatment modalities. Moreover, we have evaluated the causes of death in our DADA2 subjects together with the previously reported cases. Demographic features, clinical characteristics, imaging findings, mutations and pharmacological treatments of DADA2 subjects were noted from patient records of pediatric and adult rheumatology clinics in a retrospective and longitudinal nature. Eight patients from seven families were enrolled. While five of them were surviving, three of them had died due to various reasons. Median age of the patients at disease onset and diagnosis was 7 years (range 0.5–13 years) and 14 years (range 5–27 years), respectively. The main clinical manifestations were cutaneous findings (7/8), recurrent low-grade fever (6/8), neurological involvement (6/8) and gastrointestinal involvement (5/8). All patients had increased acute phase reactants at presentation and also during the disease flares. Until the diagnosis of DADA2 was confirmed, five patients have been followed-up with the diagnosis of PAN: two patients both with PAN and FMF, and one patient with CAPS and vasculitis. Demographic, clinical, neurological features and genetic mutations did not differ in surviving and deceased DADA2 patients. Deceased and surviving subjects differed in terms of treatment modalities after the diagnosis of DADA2. Anti-TNF alpha treatment has been initiated in five surviving patients as soon as the diagnosis of DADA2 was established. However, three patients who have died were not able to use sufficient doses of anti-TNF alpha treatment; in one case due to reluctance of patient and in two cases due to establishment of the definite diagnosis by genetic analysis at the same time with the last fatal DADA2 episode. Despite limited number of patients, this case series for the first time compares the phenotypic, genotypic and medication differences between surviving and deceased DADA2 patients. Anti-TNF alpha treatment seems to be efficient and lifesaving in DADA2 patients.

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Authors and Affiliations

Authors

Contributions

OK designed the concept of paper. SS made the literature research and wrote the paper. AA, KB, SU and HO provided critical input in data collection and processing. ETT performed genetic analysis of CECR1 gene. All of the authors have analyzed the manuscript, finally.

Corresponding author

Correspondence to Ozgur Kasapcopur.

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Conflict of interest

Author SS declares that he has no conflict of interest. Author AA declares that she has no conflict of interest. Author KB declares that he has no conflict of interest. Author SU declares that he has no conflict of interest. Author EDT declares that she has no conflict of interest. Author HO declares that she has no conflict of interest. Author ÖK declares that he has no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this study, there was no need for local ethical committee approval due to retrospective nature of the paper. All of the tests and data have been obtained from patient files.

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Informed consent was obtained from all individual participants included in the study.

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No specific funding was received from any organization for this paper.

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Sahin, S., Adrovic, A., Barut, K. et al. Clinical, imaging and genotypical features of three deceased and five surviving cases with ADA2 deficiency. Rheumatol Int 38, 129–136 (2018). https://doi.org/10.1007/s00296-017-3740-3

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  • DOI: https://doi.org/10.1007/s00296-017-3740-3

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