What is the relationship between genetic mutation and phenotypic variation in PKU?
• What aspects of treatment programs are associated with optimal long-term outcomes? Potential factors that include genetic variation, sociodemographic predictors, age, duration of treatment, and Phe levels should be studied. • Evaluation and analyses are necessary to measure the clinical utility, validation, and cost effectiveness of the use of tandem mass spectrometry for screening PKU. This evaluation should include awareness of broader issues of its application to neonatal screening for a variety of genetic disorders. • Longitudinal studies of treated PKU individuals to study effects of aging on PKU persons should be performed. • Evaluation of various modalities to increase dietary adherence in preconceptional and maternal PKU is indicated. • Studies are needed to identify the factors that enhance maintenance of metabolic control throughout life, which could be used for program development. It will be important to evaluate the effects of variations in metabolic control on cognitive
