Longitudinal Natural History of Disorders Associated with Hyperphenylalaninemia

4.项目总结--项目1 临床项目#1的目标是开发一项全面的纵向自然历史研究，以获取 新陈代谢先天疾病患者一生的结局数据 高苯丙氨酸血症(血苯丙氨酸升高)。符合条件的对象将包括所有个人 经分子证实的苯丙氨酸羟化酶(PAH)缺乏症的年龄 生物蝶呤合成或回收(包括GTP环水解酶I、6-丙酮酰-四氢蝶呤合成酶(PTPS)、 二氢蝶呤还原酶(DHPR)或蝶呤-4a-甲醇脱水酶(PCD)缺乏症)或缺乏症 多环芳烃辅助伴侣蛋白DNAJC12。该项目将全面和纵向地评估 健康、神经学、认知、神经精神病学、患者报告和生活质量结果在一大群队列中 有这些先天代谢缺陷的个体，并探索结局和 血液苯丙氨酸水平，或其他生物标志物。这项研究的结果将有助于完善和改进 目前和未来治疗最常见的先天性新陈代谢错误和罕见疾病的方法 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.