Longitudinal Natural History of Disorders Associated with Hyperphenylalaninemia

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4. PROJECT SUMMARY – PROJECT 1 The objective of Clinical Project #1 is to develop a comprehensive longitudinal natural history study to capture outcomes data throughout the lifespan on individuals with inborn errors of metabolism causing hyperphenylalaninemia (elevated blood phenylalanine (Phe)). Eligible subjects will include individuals of all ages of either gender with molecularly proven phenylalanine hydroxylase (PAH) deficiency, a deficiency of biopterin synthesis or recycling (including GTP cyclohydrolase I, 6-pyruvoyl-tetrahydropterin synthase (PTPS), dihydropteridine reductase (DHPR) or pterin-4a-carbinolamine dehydratase (PCD) deficiencies), or deficiency of the PAH co-chaperone protein DNAJC12. This project will comprehensively and longitudinally evaluate the health, neurologic, cognitive, neuropsychiatric, patient-reported, and quality-of-life outcomes in a large cohort of individuals with these inborn errors of metabolism and explore the interrelationships between outcome and blood Phe levels, or other biomarkers. The results of this study will allow refinement and improvement of current and future therapies for the most common inborn error of metabolism and the rarer conditions associated with hyperphenylalaninemia.