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. 2023 Feb;43(2):338-349.
doi: 10.1007/s10875-022-01364-9. Epub 2022 Oct 14.

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

Fahad Alabbas  1   2 , Talal Alanzi  3 , Abdulrahman Alrasheed  4 , Mohammed Essa  5 , Ghaleb Elyamany  6 , Abdulrahman Asiri  7 , Sajdi Almutairi  8 , Sulaiman Al-Mayouf  9 , Abdullatif Alenazi  10 , Danyah Alsafadi  11 , Walid Ballourah  12 , Naif Albalawi  13 , Ehab Hanafy  13 , Abdulqader Al-Hebshi  14 , Seham Alrashidi  15 , Fatma Albatniji  16 , Huda Alfaraidi  16 , Tahani Bin Ali  16 , Mansour Al Qwaiee  17 , Maryam AlHilali  18 , Hayam Aldeeb  16 , Ali Alhaidey  19 , Hassan Aljasem  20 , Sami Althubaiti  21   22   23 , Abdulrahman Alsultan  24
Affiliations

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

Fahad Alabbas et al. J Clin Immunol. 2023 Feb.

Abstract

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.

Keywords: Adenosine deaminase 2; Hodgkin lymphoma; cytopenia; immunodeficiency; stroke; vasculitis.

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