This funding opportunity announcement (FOA) encourages applications that propose to develop studies that will lead to a broad understanding of the natural history of disorders that already do or could potentially benefit from early identification by newborn screening. A comprehensive understanding of the natural history of a disorder has been identified as a necessary element to facilitate appropriate interventions for infants identified by newborn screening. By defining the sequence and timing of the onset of symptoms and complications of a disorder, a valuable resource will be developed for the field. In addition, for some disorders, specific genotype-phenotype correlations may allow prediction of the clinical course, and for other disorders, identification of modifying genetic, epigenetic, or environmental factors will enhance an understanding of the clinical outcomes for an individual with such a condition. Comprehensive data on natural history will facilitate the field;apos;s ability to: 1) accurately diagnose the disorder; 2) understand the genetic and clinical heterogeneity and phenotypic expression of the disorder; 3) identify underlying mechanisms related to basic defects; 4) potentially prevent, manage, and treat symptoms and complications of the disorder; and 5) provide children and their families with needed support and predictive information about the disorder.