From the Guidelines
Fatty acid oxidation defects (FAOD) should be managed through dietary modifications, including frequent feeding, avoiding prolonged fasting, and in some cases, supplementation with medium-chain triglycerides that can bypass the defective metabolic pathways, as well as intravenous glucose infusion of at least 10 mg/kg/min to maintain serum glucose above 100 mg/dL during a crisis 1.
Key Considerations
- Fatty acid oxidation is a key metabolic pathway for the maintenance of energy homeostasis, particularly in high-energy requiring organs such as the heart and skeletal muscle 1.
- FAOD are inherited metabolic diseases with serious life-threatening symptoms, including hypoketotic hypoglycemia, cardiomyopathy, rhabdomyolysis, encephalopathy, acute metabolic acidosis, and liver dysfunction 1.
- Triggering events for FAOD include febrile illnesses, vomiting, and fasting, which can lead to severe complications 1.
- Hepatic presentation with hypoketotic hypoglycemia and Reye-like syndrome is usually seen in infancy, but can extend into childhood and adolescence 1.
Management
- Dietary intervention is crucial in managing FAOD, and prompt intervention may reverse symptoms and preclude the need for liver transplantation (LT) 1.
- LT is an acceptable therapeutic option for patients with FAOD who present with fulminant liver failure and fail medical and dietary intervention 1.
- Carnitine plays a critical role in fatty acid metabolism, and its supplementation may be beneficial in some cases of FAOD 1.
Important Factors
- Fatty acid oxidation is highly efficient, yielding more energy per gram than carbohydrates 1.
- Disorders of fatty acid oxidation can lead to serious metabolic complications, particularly during periods of fasting or increased energy demand 1.
- Medium-chain triglycerides can bypass the defective metabolic pathways in FAOD, providing an alternative energy source 1.
From the Research
Fatty Acid Oxidation Disorders
- Fatty acid oxidation disorders (FAODs) are inborn errors of metabolism due to disruption of either mitochondrial β-oxidation or the fatty acid transport using the carnitine transport pathway 2.
- 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 3.
Clinical Manifestations
- Patients with LC-FAODs may present with rhabdomyolysis induced by exercise, fasting, or illness; hepatic dysfunction, including severe hypoglycemia and hyperammonemia; and cardiomyopathy 3.
- The presentation of a FAOD will depend upon the specific disorder, but common elements may be seen, and ultimately require a similar treatment 2.
Treatment and Management
- The treatment of all FAODs includes avoidance of fasting, aggressive treatment during illness, and supplementation of carnitine, if necessary 2.
- The long-chain FAODs differ by requiring a fat-restricted diet and supplementation of medium chain triglyceride oil and often docosahexaenoic acid (DHA) 2.
- Triheptanoin, a triglyceride oil that is broken down to acetyl-coenzyme A (CoA) and propionyl-CoA, has been shown to ameliorate acute cardiomyopathy and increase survival in patients with severe LC-FAODs 4.
- Recent US Food and Drug Administration approval of triheptanoin has improved the outcome for affected individuals 5.
Novel Therapies
- The use of medium, odd-chain fatty acids, such as triheptanoin, has been studied as a treatment of LC-FAODs due to its anaplerotic properties 3.
- A double-blind, randomized controlled trial of triheptanoin versus trioctanoin demonstrated improvement of cardiac functions on triheptanoin 6.
- Bezafibrate may be a promising drug for the treatment of FAODs, though further studies are required 6.