Ther Adv Endocrinol Metab. 2011 Jun;2(3):127-33. doi: 10.1177/2042018811402248.
Phenylketonuria (PKU) is an inherited disorder of amino acid metabolism caused by deficiency of the enzyme phenylalanine hydroxylase (PAH). Historically PKU was a common genetic cause of severe learning difficulties and developmental delay, but with the introduction of newborn screening and early dietary management, it has become a treatable disease and people born with PKU should now have IQs and achievements similar to their peers. Dietary treatment, however, involves lifestyle changes that pervade most aspects of daily life for an individual and their family. A simple pharmacological treatment for PKU would have a great appeal. Sapropterin hydrochloride is a synthetic form of tetrahydrobiopterin, the cofactor for PAH. A proportion of mutant PAH enzymes show enhanced activity in the presence of pharmacological doses of sapropterin and, for some patients with milder forms of PKU, sapropterin can effectively lower plasma phenylalanine levels. This article discusses the potential place for sapropterin in the management of PKU and how this expensive orphan drug is being integrated into patient care in different healthcare systems.
苯丙酮尿症（PKU）是一种由苯丙氨酸羟化酶（PAH）缺乏引起的氨基酸代谢遗传疾病。历史上，PKU 是导致严重学习困难和发育迟缓的常见遗传原因，但随着新生儿筛查和早期饮食管理的引入，它已成为一种可治疗的疾病，现在出生患有 PKU 的人应该具有与同龄人相似的智商和成就。然而，饮食治疗涉及到生活方式的改变，这些改变会渗透到个人和他们家庭日常生活的大多数方面。一种简单的 PKU 药理学治疗方法将具有很大的吸引力。盐酸沙丙蝶呤是四氢生物蝶呤的合成形式，是 PAH 的辅助因子。一部分突变的 PAH 酶在药理学剂量的沙丙蝶呤存在下显示出增强的活性，对于一些患有较轻形式 PKU 的患者，沙丙蝶呤可以有效地降低血浆苯丙氨酸水平。本文讨论了沙丙蝶呤在 PKU 管理中的潜在地位，以及这种昂贵的孤儿药如何在不同的医疗保健系统中融入患者护理。
