Benefits of Mutation Analysis and Examination of Brain Phenylalanine Levels in the Management of Phenylketonuria

Phenylketonuria (PKU) was first described in 1934 by Følling in Norway¹; however, the actual gene defect was not elucidated until 1983 by Woo and colleagues.² During the past 17 years, progress in assessing the usefulness of DNA analyses in the management of PKU has been obscured by the numerous mutations of the phenylalanine hydroxylase (PAH) gene that have been described to date.³The fact that routine mutational analysis for PKU is unavailable in the United States at present is attributable to several factors, but speaks forcefully to the lack of appreciation of the usefulness of DNA technology by professionals as well as that of the general public. Although mutation analyses potentially represent new powerful techniques in a wide variety of medical disorders, such as cancer, societal attitudes have been influential in delaying implementation of the resources necessary for clinical application of these new methodologies. In the case of PKU, such delays are understandable because of the need to establish a scientific background of data, which demonstrates the value of mutational analysis of the PAH gene to the practicing clinician, thereby justifying the cost to parents, as well as funding agencies. The pioneering work of Scriver and colleagues in developing the Phenylalanine Hydroxylase Locus Database³and the …