Newborn screening (NBS) is a highly successful secondary prevention program with the goal of preventing severe sequelae of congenital, mostly genetic, diseases by identifying them as early as possible, ideally in the pre-symptomatic period. Studies to date have shown the important achievements of NBS programs but also reveal a number of relevant weaknesses. These include the often incompletely understood natural history and phenotypic diversity of rare diseases as well as the inadequate …