Chief of the Division of Medical Genetics and Director of The Center for Rare Disease Therapy, UPMC Children's Hospital of Pittsburgh; and Cleveland Family Endowed Chair in Pediatric Research and Professor of Human Genetics, University of Pittsburgh, both in Pittsburgh, PA. Email:
Am J Manag Care. 2020 Aug;26(7 Suppl):S147-S154. doi: 10.37765/ajmc.2020.88480.
Long-chain fatty acid oxidation disorders (LC-FAODs) are rare, life-threatening, autosomal recessive genetic disorders characterized by acute crises of energy production and chronic energy deficiency. Patients may present with rhabdomyolysis induced by exercise; fasting or illness; hepatic dysfunction, including severe hypoglycemia and hyperammonemia; and cardiomyopathy. These clinical manifestations can lead to frequent hospitalizations and premature death. LC-FAODs are caused by mutations in nuclear genes encoding mitochondrial enzymes involved in the conversion of dietary long-chain fatty acids (LCFAs) into energy during times of fasting and physiologic stress. Despite newborn screening, current management options leave many patients continuing to experience major clinical events, and mortality rates remain elevated. The current standard therapy for LC-FAODs is avoidance of fasting and supplementation of medium-chain triglyceride oil, an even, medium-chain fatty acid that does not require the typical steps of LC-FAOD for metabolism. Despite this therapy, patients with LC-FAODs continue to experience recurring hospitalizations, and high morbidity and mortality rates. In recent years, the use of medium, odd-chain fatty acids, such as triheptanoin, have been studied as a treatment of LC-FAODs due to its anaplerotic properties. Due to favorable safety and efficacy data from clinical trials, this novel agent has the potential to transform the treatment of LC-FAODs and improve patient outcomes in this patient population. This article provides an overview of the epidemiology, pathophysiology, clinical manifestations, and current management approaches for the diagnosis and management of LC-FAODs. It also provides the most recent clinical safety and efficacy data for triheptanoin and other therapies under investigation.
长链脂肪酸氧化障碍（LC-FAODs）是一种罕见的、危及生命的常染色体隐性遗传疾病，其特征为能量生成的急性危机和慢性能量不足。患者可能表现为运动引起的横纹肌溶解症；禁食或疾病；肝功能障碍，包括严重低血糖和高血氨症；以及心肌病。这些临床表现可导致频繁住院和过早死亡。LC-FAOD 是由核基因编码的线粒体酶的突变引起的，这些酶在禁食和生理应激期间参与将膳食长链脂肪酸（LCFAs）转化为能量。尽管有新生儿筛查，但目前的管理选择仍使许多患者继续经历重大临床事件，死亡率仍然居高不下。LC-FAOD 的当前标准治疗是避免禁食和补充中链甘油三酯油，这是一种均匀的、中链脂肪酸，不需要 LC-FAOD 的典型步骤进行代谢。尽管采用了这种治疗方法，LC-FAOD 患者仍继续经历反复住院，发病率和死亡率仍然很高。近年来，由于其生酮作用，中链奇数脂肪酸，如三庚酸，已被研究作为 LC-FAOD 的治疗方法。由于临床试验的安全性和疗效数据良好，这种新型药物有可能改变 LC-FAOD 的治疗方法，并改善该患者群体的治疗结果。本文概述了 LC-FAOD 的流行病学、病理生理学、临床表现以及目前的诊断和管理方法。它还提供了三庚酸和其他正在研究的治疗方法的最新临床安全性和疗效数据。
