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A Monogenic Disease with a Variety of Phenotypes: Deficiency of Adenosine Deaminase 2.
- Source :
-
The Journal of rheumatology [J Rheumatol] 2020 Jan; Vol. 47 (1), pp. 117-125. Date of Electronic Publication: 2019 May 01. - Publication Year :
- 2020
-
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.<br />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.<br />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.<br />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 :
- Adenosine Deaminase blood
Adenosine Deaminase chemistry
Adolescent
Adult
Agammaglobulinemia blood
Anemia, Diamond-Blackfan blood
Catalytic Domain genetics
Child
Child, Preschool
Cohort Studies
Dimerization
Exons
Female
Genetic Association Studies
Genetic Predisposition to Disease
Hematopoietic Stem Cell Transplantation
Homozygote
Humans
Intercellular Signaling Peptides and Proteins blood
Intercellular Signaling Peptides and Proteins chemistry
Male
Middle Aged
Mutation
Polyarteritis Nodosa blood
Severe Combined Immunodeficiency blood
Young Adult
Adenosine Deaminase deficiency
Adenosine Deaminase genetics
Agammaglobulinemia enzymology
Anemia, Diamond-Blackfan enzymology
Intercellular Signaling Peptides and Proteins deficiency
Intercellular Signaling Peptides and Proteins genetics
Phenotype
Polyarteritis Nodosa enzymology
Severe Combined Immunodeficiency enzymology
Subjects
Details
- Language :
- English
- ISSN :
- 0315-162X
- Volume :
- 47
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The Journal of rheumatology
- Publication Type :
- Academic Journal
- Accession number :
- 31043544
- Full Text :
- https://doi.org/10.3899/jrheum.181384