1 Short-chain and medium-chain fatty acids can enter the mitochondria directly, but long-chain fatty acids (LCFAs) must be transferred in via a shuttle involving 3 enzymes/transporters and carnitine. The Role of Fatty Acids in Production of Energyįatty acids provide a major energy source for the myocardium, skeletal muscle, and liver via β-oxidation, which occurs in the mitochondria. It also provides the most recent clinical safety and efficacy data for triheptanoin and other therapies under investigation. This article provides an overview of the epidemiology, pathophysiology, clinical manifestations, and current management approaches for the diagnosis and management of LC-FAODs. 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. 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. Despite this therapy, patients with LC-FAODs continue to experience recurring hospitalizations, and high morbidity and mortality rates. 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 newborn screening, current management options leave many patients continuing to experience major clinical events, and mortality rates remain elevated. 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. These clinical manifestations can lead to frequent hospitalizations and premature death. Patients may present with rhabdomyolysis induced by exercise fasting or illness hepatic dysfunction, including severe hypoglycemia and hyperammonemia and cardiomyopathy. 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.
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