ABSTRACT
The basic-science investment o f this society in the study o f human diseases has yielded an understanding o f the molecular pathologies o f many inherited metabolic disorders. By 1993, molecular defects in catalytic, receptor, trans port, or structural proteins had been identified for more than 200 inborn errors o f metabolism (1). This information permits the unambiguous diagnosis of these disorders, either prenatally or shortly after the onset o f symptoms early in life. Some of these disorders involve defects in only a single gene product, whose expression is often limited to a single tissue type. For these disorders, previous biochemical-based studies often led to the development o f conven tional therapies that have been relatively successful in treating the more serious consequences o f these diseases. Two examples o f disorders o f this type include the monogenic diseases phenylketonuria (PKU), caused by a deficiency o f the hepatic enzyme phenylalanine hydroxylase (PAH), and hemophilia B, caused by a functional deficiency of factor IX (FIX), an essential cofactor in the intrinsic coagulation pathway.
