Genotype and Phenotype of Adenosine Deaminase 2 Deficiency: a Report from Saudi Arabia

Adenosine deaminase 2 deficiency (DADA2), a rare and potentially fatal systemic autoinflammatory disease, is characterized by low or lack of ADA2 activity due to ADA2 mutations. DADA2 symptoms are variable and include vasculitis, immunodeficiency, and cytopenia. Minimal data are available from Saudi...

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Published in:	Journal of clinical immunology Vol. 43; no. 2; pp. 338 - 349
Main Authors:	Alabbas, Fahad, Alanzi, Talal, Alrasheed, Abdulrahman, Essa, Mohammed, Elyamany, Ghaleb, Asiri, Abdulrahman, Almutairi, Sajdi, Al-Mayouf, Sulaiman, Alenazi, Abdullatif, Alsafadi, Danyah, Ballourah, Walid, Albalawi, Naif, Hanafy, Ehab, Al-Hebshi, Abdulqader, Alrashidi, Seham, Albatniji, Fatma, Alfaraidi, Huda, Ali, Tahani Bin, Al Qwaiee, Mansour, AlHilali, Maryam, Aldeeb, Hayam, Alhaidey, Ali, Aljasem, Hassan, Althubaiti, Sami, Alsultan, Abdulrahman
Format:	Journal Article
Language:	English
Published:	New York Springer US 01-02-2023 Springer Nature B.V
Subjects:	Adenosine Adenosine Deaminase Biomedical and Life Sciences Biomedicine Blood transfusion Colony-stimulating factor Cyclosporins Cytopenia Genotype Genotypes Growth rate Hematology Hematopoietic stem cells Hepatitis Hodgkin's lymphoma Humans Immunodeficiency Immunology Infectious Diseases Inflammatory diseases Intercellular Signaling Peptides and Proteins - genetics Internal Medicine Medical Microbiology Mutation Mutation - genetics Myelitis Original Article Patients Phenotype Phenotypes Recurrent infection Retrospective Studies Saudi Arabia Splenectomy Stem cell transplantation Tumor necrosis factor Tumor Necrosis Factor Inhibitors Tumor necrosis factor-TNF Vasculitis Vasculitis - etiology Saudi Arabia Adenosine deaminase 2 immunodeficiency cytopenia vasculitis stroke Hodgkin lymphoma
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Summary:	Adenosine deaminase 2 deficiency (DADA2), a rare and potentially fatal systemic autoinflammatory disease, is characterized by low or lack of ADA2 activity due to ADA2 mutations. DADA2 symptoms are variable and include vasculitis, immunodeficiency, and cytopenia. Minimal data are available from Saudi Arabia. This retrospective study conducted at seven major tertiary medical centers examined the phenotypic and genotypic variabilities, clinical and diagnostic findings, and treatment outcomes among 20 Saudi patients with DADA2 from 14 families. The median age of the study cohort was 9.5 years (4–26 years). The clinical presentation was before the age of 5 months in 25% of patients. Homozygous c.1447-1451del mutation was the most frequent ADA2 alteration (40%), followed by c.882-2A:G (30%). All tested patients exhibited absent or near-absent ADA2 activity. Phenotypic manifestations included stroke (40%), hematological abnormalities (95%), lymphoproliferation (65%), and recurrent infection (45%). Five and three patients had extracranial vasculitis features and Hodgkin lymphoma, respectively. Atypical manifestations included growth retardation (30%) and transverse myelitis. Anti-tumor necrosis factor (anti-TNF) therapy was the main treatment. Some patients underwent blood transfusion, splenectomy, cyclosporine and colony-stimulating factor therapies, and hematopoietic stem cell transplantation due to anti-TNF therapy failure. Fulminant hepatitis and septic multiorgan failure caused mortality in three patients. Thus, this study revealed the variability in the molecular and clinical characteristics of DADA2 in the study cohort with predominant aberrant hematological and immunological characteristics. Consensus diagnostic criteria will facilitate early diagnosis and treatment. Additionally, disease registries or large prospective studies are needed for evaluating rare disease complications, such as cancer.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0271-9142 1573-2592
DOI:	10.1007/s10875-022-01364-9