Abstract：
Alkaptonuria (AKU, OMIM, No. 203500) is a rare, slow-progressing, irreversible, multisystemic disease resulting from a deficiency of the homogentisate 1,2-dioxygenase enzyme, which leads to the accumulation of homogentisic acid (HGA) and subsequent deposition as pigment in connective tissues called ochronosis. As a result, severe arthropathy of large joints and spondyloarthropathy with frequent fractures, ligament ruptures, and osteoporosis develops in AKU patients. Since 2020, the first-time treatment with nitisinone has become available in the European Union. Nitisinone significantly reduces HGA production and arrests ochronosis in AKU patients. However, blocking of the tyrosine metabolic pathway by the drug leads to tyrosine plasma and tissue concentrations increase. The nitisinone-induced hypertyrosinemia can lead to the development of corneal keratopathy, and once it develops, the treatment needs to be interrupted. A decrease in overall protein intake reduces the risk of the keratopathy during nitisinone-induced hypertyrosinemia in AKU patients. The low-protein diet is not only poorly tolerated by patients, but over longer periods, leads to a severe muscle loss and weight gain due to increased energy intake from carbohydrates and fats. Therefore, the development of novel nutritional approaches is required to prevent the adverse events due to nitisinone-induced hypertyrosinemia and the negative impact on skeletal muscle metabolism in AKU patients.
摘要：
碱尿症（AKU，OMIM,不。203500）是一种罕见的，进展缓慢,不可逆转的,由匀浆1,2-双加氧酶缺乏引起的多系统疾病，这导致均质酸（HGA）的积累，并随后在结缔组织中以色素的形式沉积，称为慢性疾病。因此,严重的大关节关节病和脊柱关节病频繁骨折，韧带断裂,在AKU患者中发生骨质疏松症。自2020年以来，首次使用尼替辛酮治疗已在欧盟上市。Nitisinone显着减少了AKU患者的HGA产生并阻止了慢性疾病。然而,药物对酪氨酸代谢途径的阻断导致酪氨酸血浆和组织浓度增加。Nitisinone诱导的高酪氨酸血症可导致角膜角膜病变的发展，一旦它发展起来，治疗需要中断。总体蛋白质摄入量的减少降低了AKU患者Nitisinone诱导的高酪氨酸血症期间角膜病变的风险。低蛋白饮食不仅患者耐受性差,但是在更长的时间里，由于碳水化合物和脂肪的能量摄入增加，导致严重的肌肉损失和体重增加。因此,在AKU患者中,需要开发新的营养方法,以预防因Nitisinone诱导的高酪氨酸血症引起的不良事件以及对骨骼肌代谢的负面影响.
