Purpose of review: To recap the expanding clinical spectrum, genotype-phenotype associations and treatment options in the light of recently published articles regarding the deficiency of adenosine deaminase 2 (DADA2).
Recent findings: Whole-exome sequencing enabled novel clinical phenotypes associated with ADA2 mutations. Since its discovery, the phenotypic spectrum of DADA2 has substantially expanded to cover Diamond-Blackfan anaemia, cytopenia and immunodeficiency syndromes. In addition to elevated TNF alpha levels, increased levels of interferon-stimulated genes were also detected in patients with DADA2. Given the absence of clinical trials until now, no standard treatment strategy exists for DADA2. Currently, anti-TNF alpha agents are the mainstay of treatment, based on the data both from the initial two reports and from subsequent studies. However, it is still unclear how to manage asymptomatic patients with ADA2 mutation and/or with absent ADA2 activity and what is the optimal duration of anti-TNF therapy.
Summary: Among a total of 206 DADA2 patients described so far, the overall mortality was found as 8.3%. Biallelic homozygous G47R mutations were mostly associated with a vascular phenotype, whereas patients with homozygous R169Q mutations seem to display a mixed clinical phenotype including vascular, haematological and immunological manifestations. HSCT should be reserved as a curative treatment option for DADA2 patients unresponsive to the anti-TNF therapy, as it carries a significant morbidity.