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A Monogenic Disease with a Variety of Phenotypes: Deficiency of Adenosine Deaminase 2
- Source :
- The Journal of Rheumatology. 47:117-125
- Publication Year :
- 2019
- Publisher :
- The Journal of Rheumatology, 2019.
-
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.
- Subjects :
- Male
0301 basic medicine
Adenosine Deaminase 2 Deficiency
genetic structures
Adenosine Deaminase
medicine.disease_cause
Cohort Studies
0302 clinical medicine
Agammaglobulinemia
Catalytic Domain
Immunology and Allergy
Diamond–Blackfan anemia
Child
Immunodeficiency
Anemia, Diamond-Blackfan
Mutation
Hematology
Homozygote
Hematopoietic Stem Cell Transplantation
Exons
Adenosıne deamınase 2 defıcıency
Middle Aged
Phenotype
Child, Preschool
Polyarteritis nodosa pure red cell anemia
Intercellular Signaling Peptides and Proteins
Female
Dimerization
Adult
medicine.medical_specialty
Adolescent
Diamond-blackfan anemia
Anemia
Immunology
Young Adult
03 medical and health sciences
Rheumatology
Internal medicine
medicine
Humans
Genetic Predisposition to Disease
Tıp uygulaması
Genetic Association Studies
030203 arthritis & rheumatology
Thrombocytosis
business.industry
Polyarteritis nodosa
medicine.disease
Polyarteritis Nodosa
030104 developmental biology
Severe Combined Immunodeficiency
business
Subjects
Details
- ISSN :
- 14992752 and 0315162X
- Volume :
- 47
- Database :
- OpenAIRE
- Journal :
- The Journal of Rheumatology
- Accession number :
- edsair.doi.dedup.....049cafbcbee17a980a573e7e222d7aca