We aimed to test the relevance of deficiency of adenosine deaminase 2 (DADA2) in patients with antibody deficiency and describe the clinical picture of the disease in adulthood.
We screened for DADA2 in a cohort of 181 patients with antibody deficiency with or without vascular lesions using next-generation sequencing and targeted Sanger sequencing. All mutations were confirmed by determining the ADA2 enzymatic activity levels in dried plasma spots. Clinical data and laboratory values were collected in a standardized format.
Following the diagnosis of 2 siblings in the index family, we identified 9 additional affected patients with compound heterozygous or homozygous CECR1 mutations, containing 6 novel and 4 previously published mutations. The patients' age at evaluation ranged from 13 to 51 years, with a median age of 22 years. Clinically, we saw a broad phenotype, ranging from isolated antibody deficiency to recurrent strokes. All but 1 patient had low numbers of memory B cells. Moreover, B cell function seemed to correlate with inflammation.
Taken together, our findings indicate that DADA2 presents not only with vasculopathy but also with an immunodeficiency of the B cell compartment. Therefore, patients with antibody deficiency should be screened for DADA2. Anti-tumor necrosis factor treatment might improve immunologic features over time and might be considered in patients without vascular manifestations but with elevated inflammation markers. Conservative management has so far proven to be the choice for our less severely affected adolescent and adult DADA2 patients; however, in patients with severe cytopenias and bone marrow failure, hematopoietic stem cell transplantation should be considered.