We propose to characterize the etiology and natural history of rare inborn errors of metabolism and other genetic disorders, both known and yet-to-be discovered. In so doing, we will expand our knowledge about these disorders and provide access to patients of interest for research, teaching, and clinical experience. Individual patients seen under this protocol have prompted the establishment of specific disease-related protocols involving intensive natural history studies and innovative therapies. In addition to its longstanding role in investigating individuals who are of interest to the Section on Human Biochemical Genetics, this protocol provides one possible avenue (in addition to other NIH protocols) for admitting patients who are part of the NIH Undiagnosed Diseases Program.