Linking genetics to recurrent strokes in children with DADA2
Sometimes, the clinical presentation of a disease and its underlying genetics are difficult to link, which can make successful treatment extremely challenging. Such was the case with Deficiency of ADA2 (DADA2), where the connection between its genetic variant and childhood symptoms of recurrent strokes remained a mystery.
IRP teams led by Manfred Boehm, M.D., and Daniel Kastner, M.D., Ph.D., developed in vitro disease modeling studies that identified the ADA2 gene as a key regulator in monocyte/macrophage differentiation, which leads to endothelial cell activation and damage that is a likely disease mechanism for the recurrent strokes in children with DADA2.
The finding provides new insights into the causes of strokes in children and the role of ADA2 in inflammatory vasculopathies. As a result, children with DADA2 were not treated with standard blood thinners, but were treated with TNF inhibition, which greatly improved the lives of both the affected children and their families.
Zhou Q, Yang D, Ombrello AK, et al. (2014). Early-onset stroke and vasculopathy associated with mutations in ADA2. N Engl J Med. 370(10):911-20.