This proposed research concerns the study of the metabolic errors of amino-acids and related compounds in humans. Individuals studied will include those who are mentally retarded or have other neurological abnormalities as well as those who have other metabolic abnormalities. In addition, infants diagnosed as having metabolic disorders on the basis of biochemical abnormalities detected by population (newborn) screening will also be studied. These disorders include the sulfur amino acid abnormalities, a defect in folate metabolism, the hyperglycinemias, maternal phenylketonuria, and others as well as renal transport defects such as cystinuria and Hartnup disease. We will also study amino acid metabolism in animals as well as in cell culture derived from skin and amniotic fluid as a means of better understanding human metabolism and disease.