Fatty acid oxidation disorders (FAODs) are rare, inherited metabolic conditions that prevent the body from converting stored fats into energy. These disorders occur when enzymes needed to break down fatty acids are missing or don’t function properly. While the body primarily uses glucose for energy, it relies on fat during fasting or illness. When this system is impaired, the body cannot produce sufficient energy, and harmful byproducts can accumulate.
Genetic Inheritance of FAODs
FAODs follow an autosomal recessive inheritance pattern. This means a child must inherit one non-working gene copy from each parent to develop the disorder. Parents who carry one non-working and one normal gene are typically healthy and do not show symptoms themselves.
With each pregnancy, carrier parents have a 25% chance of having a child affected by a FAOD, and a 50% chance their child will be an unaffected carrier like themselves. These genetic mutations disrupt the function of enzymes or transport proteins involved in the fatty acid oxidation pathway.
Symptoms and Health Complications
The symptoms of FAODs can vary, depending on the specific type of disorder and the individual’s age. Problems often emerge in early childhood, triggered by periods of fasting, such as sleeping through the night, or during illnesses that cause vomiting or reduced food intake. During these times, the body’s primary energy source, glucose, becomes depleted, leading to reliance on fat metabolism. When fat cannot be properly broken down, individuals may experience symptoms like lethargy, persistent vomiting, poor feeding, and dangerously low blood sugar (hypoglycemia).
If unmanaged, acute episodes can progress to severe complications, including seizures, coma, and sudden death. Beyond acute crises, FAODs can lead to long-term health issues affecting various organs. These complications include liver dysfunction, heart muscle damage (cardiomyopathy or arrhythmias), and skeletal muscle problems such as weakness, pain (myalgia), or breakdown (rhabdomyolysis). Rhabdomyolysis can cause dark urine due to muscle protein release.
Diagnosis and Newborn Screening
Identifying FAODs early is important for improving health outcomes. Newborn screening programs detect these conditions shortly after birth, typically through a heel prick test. A few drops of blood are collected from the baby, usually between 24 to 48 hours of age, and analyzed using tandem mass spectrometry.
This method measures acylcarnitine levels, which indicate problems with fat metabolism. An abnormal newborn screening result suggests a higher risk, prompting further evaluation. Follow-up diagnostic tests may include additional blood and urine analyses for specific metabolic markers, along with genetic testing to identify the gene mutation causing the disorder.
Treatment and Lifestyle Management
Managing a diagnosed FAOD primarily revolves around dietary and lifestyle adjustments to ensure a consistent energy supply. A central strategy is preventing prolonged periods of fasting, which can trigger metabolic crises. This often means regular, frequent meals and snacks, even waking infants and young children during the night to feed them. During illness, when appetite may decrease, it is particularly important to maintain caloric intake.
Dietary management typically involves a low-fat, high-carbohydrate diet to minimize the body’s reliance on fat for energy. For specific types of FAODs, especially long-chain disorders, special medical foods or supplements like medium-chain triglyceride (MCT) oil may be prescribed. MCT oil provides an alternative fat source that can be metabolized more easily, but it is contraindicated in short- and medium-chain FAODs.
Individuals with FAODs should have a clear emergency protocol for times of illness or increased metabolic demand. This protocol often includes immediately administering easily digestible carbohydrates, such as fruit or cornstarch, and seeking medical attention if oral intake is not tolerated. In a hospital setting, intravenous glucose is often administered to quickly provide energy and prevent severe complications. Some patients may also benefit from carnitine supplementation, which helps remove accumulating fatty acid byproducts from the body.