Harding Cary O
Departments of Molecular and Medical Genetics and Pediatrics, Oregon Health & Science University, Portland, Oregon, USA.
Biologics. 2010 Aug 9;4:231-6. doi: 10.2147/btt.s3015.
Oral administration of sapropterin hydrochloride, recently approved for use by the US Food and Drug Administration and the European Commission, is a novel approach for the treatment of phenylketonuria (PKU), one of the most common inborn errors of metabolism. PKU is caused by an inherited deficiency of the enzyme phenylalanine hydroxylase (PAH), and the pathophysiology of the disorder is related to chronic accumulation of the free amino acid phenylalanine in tissues. Contemporary therapy is based upon restriction of dietary protein intake, which leads to reduction of blood phenylalanine levels. This therapy is difficult to maintain throughout life, and dietary noncompliance is commonplace. Sapropterin dihydrochloride is a synthetic version of tetrahydrobiopterin, the naturally occurring pterin cofactor that is required for PAH-mediated phenylalanine hydroxylation. In a subset of individuals with PAH deficiency, sapropterin administration leads to reduction in blood phenylalanine levels independent of dietary protein. For these individuals, sapropterin is an effective novel therapy for PKU.
盐酸沙丙蝶呤最近已获美国食品药品监督管理局和欧盟委员会批准口服使用，它是治疗苯丙酮尿症（PKU）的一种新方法，苯丙酮尿症是最常见的先天性代谢缺陷病之一。苯丙酮尿症由遗传性苯丙氨酸羟化酶（PAH）缺乏引起，该疾病的病理生理学与游离氨基酸苯丙氨酸在组织中的慢性蓄积有关。当代治疗方法基于限制膳食蛋白质摄入，这会导致血液中苯丙氨酸水平降低。这种疗法在一生中难以维持，饮食不依从很常见。盐酸沙丙蝶呤是四氢生物蝶呤的合成形式，四氢生物蝶呤是PAH介导的苯丙氨酸羟化所需的天然存在的蝶呤辅因子。在一部分PAH缺乏的个体中，服用沙丙蝶呤可使血液中苯丙氨酸水平降低，且与膳食蛋白质无关。对于这些个体，沙丙蝶呤是一种治疗苯丙酮尿症的有效新疗法。
