Longitudinal Natural History of Disorders Associated with Hyperphenylalaninemia

4.项目摘要-项目1 临床项目#1的目标是开发一项全面的纵向自然史研究，以捕获 结果数据在整个生命周期的个人与先天性代谢缺陷， 高苯丙氨酸血症（血苯丙氨酸（Phe）升高）。合格的受试者将包括所有 年龄的任何性别与分子证明苯丙氨酸羟化酶（PAH）缺乏症，缺乏 生物蝶呤合成或再循环（包括GTP环化水解酶I，6-异戊酰-四氢蝶呤合酶（PTPS）， 二氢蝶啶还原酶（DHPR）或蝶呤-4 α-甲醇胺脱氢酶（PCD）缺乏），或缺乏 PAH辅助分子伴侣蛋白DNAJC 12。本项目将全面、纵向地评估 一个大型队列的健康、神经系统、认知、神经精神、患者报告和生活质量结局 的个体与这些先天性代谢缺陷，并探讨结果之间的相互关系， 血液Phe水平或其他生物标志物。这项研究的结果将允许细化和改进 最常见的先天性代谢缺陷和罕见疾病的当前和未来疗法 与高苯丙氨酸血症有关

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.