Ah Mew Nicholas, Lichter-Konecki Uta
Center for Precision Medicine and Genomics Research, Children's National Hospital, Washington, DC, USA.
Division of Genetic and Genomic Medicine, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, 4401 Penn Ave, Pittsburgh, PA, 15224, USA.
Paediatr Drugs. 2025 Sep 22. doi: 10.1007/s40272-025-00719-0.
The urea cycle, a metabolic pathway comprising six enzymes and two transporters, is necessary for mammalian nitrogen detoxification. A deficiency of any of these components disrupts this process, leading to the accumulation of nitrogen in the form of ammonia, which is especially toxic to the brain. For decades, treatment of urea cycle disorders has consisted of nitrogen scavengers, dietary protein restriction, arginine or citrulline supplementation, calorie support, and liver transplant. In 2011, carglumic acid became available as a substitute for N-acetylglutamate for N-acetylglutamate synthase deficiency. The past 10 years, however, have seen the development of enzyme therapy for arginase deficiency and gene therapy for ornithine transcarbamylase deficiency. This article reviews the current status and availability of treatment options for urea cycle disorders.
尿素循环是一条由六种酶和两种转运体组成的代谢途径，对哺乳动物的氮解毒至关重要。这些成分中的任何一种缺乏都会破坏这一过程，导致氨形式的氮积累，而氨对大脑具有特别的毒性。几十年来，尿素循环障碍的治疗方法包括氮清除剂、饮食蛋白质限制、精氨酸或瓜氨酸补充、热量支持以及肝移植。2011年，卡谷氨酸作为N - 乙酰谷氨酸合酶缺乏症中N - 乙酰谷氨酸的替代品开始可用。然而，在过去十年中，已经出现了针对精氨酸酶缺乏症的酶疗法和针对鸟氨酸转氨甲酰酶缺乏症的基因疗法。本文综述了尿素循环障碍治疗选择的现状和可用性。
