Unravelling the genetic cause of life-threatening infection in previously healthy children: the “cold-case” project

Despite the progress in living circumstances, in medicine in general and intensive care medicine in particular, some previously healthy children are still dying of or almost succumbing to infection with pathogens that only cause mild illness in most children. A retrospective survey at the University Hospitals Leuven has identified around 10 children with fatal or near-fatal infections per year. It is very likely that these children suffer from a novel or known inborn error of immunity rendering them extremely susceptible to infection with one or more pathogens. Indeed, in the last few decades, especially through the efforts of the Human Genetics of Infectious Diseases Laboratory, led by Professor Casanova, a growing number of monogenetic disorders have been identified in which previously healthy children present with a severe infectious phenotype. The aim of this project is to identify known or novel monogenetic causes of susceptibility to life-threatening infection. This project is important for many reasons. First, it will kindle the targeted screening and investigation of patients presenting with life-threatening infection. This may allow tailoring of treatment of such infections thereby helping to prevent adverse outcome. Second, it will help in counselling families and where indicated it will allow for definitive treatment also of affected family members. Lastly, it will contribute to our understanding of microbiology and immunology.