 Discovery of genetic basis of impaired metabolism has greatly advanced treatment of patients with known metabolic diseases. However, many more genetic and metabolic disorders and their molecular causes remain to be discovered. The overall goal of this study is to discover new disease-associated genes in children, while establishing a specific focus on metabolic disorders where molecular characterization is most likely to lead to novel therapies. The primary objective is to identify novel pathogenic mutations in children with rare Mendelian disorders. The secondary objectives are: 1 Optimize methodology for metabolomic sample collection, processing and analysis; and 2 Establish normative ranges for a large number potentially up to 1000 of metabolites in healthy newborns and older children. 