Seza Özen1,2, Ezgi Deniz Batu3,4, Ekim Z Taşkıran3,4, Hatice Asuman Özkara3,4, Şule Ünal3,4, Naz Güleray3,4, Abdulsamet Erden3,4, Ömer Karadağ3,4, Fatma Gümrük3,4, Mualla Çetin3,4, Hafize Emine Sönmez3,4, Yelda Bilginer3,4, Deniz Çağdaş Ayvaz3,4, Ilhan Tezcan3,4. 1. From the Division of Rheumatology, Department of Pediatrics, Division of Immunology, Department of Internal Medicine, Department of Medical Genetics, Department of Medical Biochemistry, Hacettepe University Faculty of Medicine; Hacettepe University Center for Fanconi Anemia and Other Inherited Bone Marrow Failure Syndromes, Ankara, Turkey. sezaozen@gmail.com. 2. S. Özen, MD, Division of Rheumatology, Department of Pediatrics, Hacettepe University Faculty of Medicine; Y. Bilginer, MD, Division of Rheumatology, Department of Pediatrics, Hacettepe University Faculty of Medicine; E.D. Batu, MD, Division of Rheumatology, Department of Pediatrics, Hacettepe University Faculty of Medicine; E.Z. Taşkıran, PhD, Department of Medical Genetics, Hacettepe University Faculty of Medicine; H.A. Özkara, MD, PhD, Department of Medical Biochemistry, Hacettepe University Faculty of Medicine; Ş. Ünal, MD, Hacettepe University Center for Fanconi Anemia and Other Inherited Bone Marrow Failure Syndromes; N. Güleray, MD, Department of Medical Genetics, Hacettepe University Faculty of Medicine; A. Erden, MD, Division of Rheumatology, Department of Internal Medicine, Hacettepe University Faculty of Medicine; Ö. Karadağ, MD, Division of Rheumatology, Department of Internal Medicine, Hacettepe University Faculty of Medicine; F. Gümrük, MD, Hacettepe University Center for Fanconi Anemia and Other Inherited Bone Marrow Failure Syndromes; M. Çetin, MD, Hacettepe University Center for Fanconi Anemia and Other Inherited Bone Marrow Failure Syndromes (retired); H.E. Sönmez, MD, Division of Rheumatology, Department of Pediatrics, Hacettepe University Faculty of Medicine; D.Ç. Ayvaz, MD, Division of Immunology, Department of Pediatrics, Hacettepe University Faculty of Medicine; I. Tezcan, MD, Division of Immunology, Department of Pediatrics, Hacettepe University Faculty of Medicine. E.D. Batu and E.Z. Taşkıran contributed equally to this study. sezaozen@gmail.com. 3. From the Division of Rheumatology, Department of Pediatrics, Division of Immunology, Department of Internal Medicine, Department of Medical Genetics, Department of Medical Biochemistry, Hacettepe University Faculty of Medicine; Hacettepe University Center for Fanconi Anemia and Other Inherited Bone Marrow Failure Syndromes, Ankara, Turkey. 4. S. Özen, MD, Division of Rheumatology, Department of Pediatrics, Hacettepe University Faculty of Medicine; Y. Bilginer, MD, Division of Rheumatology, Department of Pediatrics, Hacettepe University Faculty of Medicine; E.D. Batu, MD, Division of Rheumatology, Department of Pediatrics, Hacettepe University Faculty of Medicine; E.Z. Taşkıran, PhD, Department of Medical Genetics, Hacettepe University Faculty of Medicine; H.A. Özkara, MD, PhD, Department of Medical Biochemistry, Hacettepe University Faculty of Medicine; Ş. Ünal, MD, Hacettepe University Center for Fanconi Anemia and Other Inherited Bone Marrow Failure Syndromes; N. Güleray, MD, Department of Medical Genetics, Hacettepe University Faculty of Medicine; A. Erden, MD, Division of Rheumatology, Department of Internal Medicine, Hacettepe University Faculty of Medicine; Ö. Karadağ, MD, Division of Rheumatology, Department of Internal Medicine, Hacettepe University Faculty of Medicine; F. Gümrük, MD, Hacettepe University Center for Fanconi Anemia and Other Inherited Bone Marrow Failure Syndromes; M. Çetin, MD, Hacettepe University Center for Fanconi Anemia and Other Inherited Bone Marrow Failure Syndromes (retired); H.E. Sönmez, MD, Division of Rheumatology, Department of Pediatrics, Hacettepe University Faculty of Medicine; D.Ç. Ayvaz, MD, Division of Immunology, Department of Pediatrics, Hacettepe University Faculty of Medicine; I. Tezcan, MD, Division of Immunology, Department of Pediatrics, Hacettepe University Faculty of Medicine. E.D. Batu and E.Z. Taşkıran contributed equally to this study.
Abstract
OBJECTIVE: Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive autoinflammatory disorder associated with ADA2 mutations. We aimed to investigate the characteristics and ADA2 enzyme activities of patients with DADA2 compared to non-DADA2 patients. METHODS: This is a descriptive study of 24 patients with DADA2 who were admitted to the Adult and Pediatric Rheumatology, Pediatric Haematology, and Pediatric Immunology Departments of Hacettepe University. All ADA2 exons were screened by Sanger sequencing. Serum ADA2 enzyme activity was measured by modified spectrophotometric method. RESULTS: Twenty-four patients with DADA2 were included: 14 with polyarteritis nodosa (PAN)-like phenotype (Group 1); 9 with Diamond-Blackfan anemia (DBA)-like features, and 1 with immunodeficiency (Group 2). Fourteen PAN-like DADA2 patients did not have the typical thrombocytosis seen in classic PAN. Inflammatory attacks were evident only in Group 1 patients. Serum ADA2 activity was low in all patients with DADA2 except one, who was tested after hematopoietic stem cell transplantation. There was no significant difference in ADA2 activities between PAN-like and DBA-like patients. In DADA2 patients with one ADA2 mutation, serum ADA2 activities were as low as those of patients with homozygote DADA2. ADA2 activities were normal in non-DADA2 patients. ADA2 mutations were affecting the dimerization domain in Group 1 patients and the catalytic domain in Group 2 patients. CONCLUSION: We suggest assessing ADA2 activity along with genetic analysis because there are patients with one ADA2 mutation and absent enzyme activity. Our data suggest a possible genotype-phenotype correlation in which dimerization domain mutations are associated with PAN-like phenotype, and catalytic domain mutations are associated with hematological manifestations.
OBJECTIVE: Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive autoinflammatory disorder associated with ADA2 mutations. We aimed to investigate the characteristics and ADA2 enzyme activities of patients with DADA2 compared to non-DADA2 patients. METHODS: This is a descriptive study of 24 patients with DADA2 who were admitted to the Adult and Pediatric Rheumatology, Pediatric Haematology, and Pediatric Immunology Departments of Hacettepe University. All ADA2 exons were screened by Sanger sequencing. Serum ADA2 enzyme activity was measured by modified spectrophotometric method. RESULTS: Twenty-four patients with DADA2 were included: 14 with polyarteritis nodosa (PAN)-like phenotype (Group 1); 9 with Diamond-Blackfan anemia (DBA)-like features, and 1 with immunodeficiency (Group 2). Fourteen PAN-like DADA2 patients did not have the typical thrombocytosis seen in classic PAN. Inflammatory attacks were evident only in Group 1 patients. Serum ADA2 activity was low in all patients with DADA2 except one, who was tested after hematopoietic stem cell transplantation. There was no significant difference in ADA2 activities between PAN-like and DBA-like patients. In DADA2 patients with one ADA2 mutation, serum ADA2 activities were as low as those of patients with homozygote DADA2. ADA2 activities were normal in non-DADA2 patients. ADA2 mutations were affecting the dimerization domain in Group 1 patients and the catalytic domain in Group 2 patients. CONCLUSION: We suggest assessing ADA2 activity along with genetic analysis because there are patients with one ADA2 mutation and absent enzyme activity. Our data suggest a possible genotype-phenotype correlation in which dimerization domain mutations are associated with PAN-like phenotype, and catalytic domain mutations are associated with hematological manifestations.
Entities:
Keywords:
ADENOSINE DEAMINASE 2 DEFICIENCY; DIAMOND-BLACKFAN ANEMIA; POLYARTERITIS NODOSA PURE RED CELL ANEMIA
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