OBJECTIVES : Deficiency of adenosine deaminase 2 (DADA2) is a fatal autosomal recessive disease characterised by failure to thrive, impaired immune responses, and recurrent infections. This systematic literature review (SLR) aimed to evaluate the clinical management of patients with DADA2.

METHODS : Clinical trials and real-world studies including patients with DADA2 and their treatment were identified from Embase, Medline, and Cochrane from database inception to June 2021. The SLR was in accordance with the Cochrane and NICE methodologies.

RESULTS : Thirty-one studies were included in the review. The common clinical therapies included: haematopoietic stem cell transplantation (HSCT), enzyme replacement therapy (ERT), gene therapy (GT) and anti-tumour necrosis factor (TNF)/biologics. Management with HSCT resulted in overall survival (OS) rates ranging from 63–88% with a follow-up of up to 12 years. Improved survival was reported for transplantation involving a matched sibling/family member (OS: 81–86%) as compared to unrelated/haploidentical donors (OS: 43–66%) over a median follow-up of 6.5 years. Treatment with ERT showed OS rates between 65–100% over a follow up period ranging from 8.5–26 years. Patients on GT showed varied efficacy with OS rate of 67–100% across studies, and accounted for highest treatment discontinuation rate (30–90%) for follow-up of 12 years. Anti-TNF resulted in significant reduction in stroke events from cumulative 191 to 0 events (pre-vs post-treatment) with a 0% recurrence rate. A non-randomised study comparing GT versus HSCT reported improved OS (100% vs 88%) and EFS (100% vs 56%) rates in favour of GT at 2-years of follow-up. Adverse events included neutropenia (~20%) with GT; infection (~50%) with HSCT, inflammatory skin manifestations and neutropenia (~60%) with anti-TNF therapy; none with ERT.

CONCLUSIONS : Evidence for clinical management of DADA2 is scarce and varies with the treating physician. Further research with head-to-head clinical trials is needed.