Abstract：
Alkaptonuria (AKU) is an ultra-rare inherited inborn error of metabolism that afflicts the tyrosine metabolic pathway, resulting in the accumulation of homogentisic acid (HGA) in the circulation, and significant excretion in urine. Clinical manifestations, typically observed from the third decade of life, are lifelong and significantly affect the quality of life. This review provides a comprehensive overview of the natural history of AKU, including clinical, biochemical and genetic perspectives. An update on the major advances on studies in murine models and human subjects, providing mechanistic insight into the molecular and biochemical processes that underlie pathophysiology and its response to treatment are presented. The impact of treatment with nitisinone is also presented with a specific emphasis on hypertyrosinemia, as uncertainty on this topic remains. Future perspectives are explored, such as novel approaches to treat hypertyrosinemia including the use of binding agents and amino acid transporter inhibitors, as well as advanced potentially curative gene and cell therapy initiatives.
摘要：
Alkaptonuria（AKU）是一种非常罕见的遗传性先天性代谢错误，影响酪氨酸代谢途径，导致循环中的均质酸（HGA）的积累，和大量的尿液排泄。临床表现,通常从生命的第三个十年开始观察，是终身的，显著影响生活质量。这篇综述全面概述了AKU的自然史，包括临床，生化和遗传观点。关于鼠类模型和人类受试者研究的最新进展，提出了对病理生理学基础的分子和生化过程及其对治疗的反应的机械见解。尼替辛酮治疗的影响还特别强调高酪氨酸血症，因为这个话题的不确定性仍然存在。探索未来的前景，例如治疗高酪氨酸血症的新方法，包括使用结合剂和氨基酸转运蛋白抑制剂，以及先进的潜在治愈基因和细胞治疗计划。
