Fatty acid oxidation disorders (FAODs) are a group of inherited metabolic conditions where the body cannot properly break down certain fats to produce energy. This process involves a series of steps, each requiring specific enzymes. When one of these enzymes is deficient or absent, the body struggles to convert fats into usable energy.
Fatty acids are a significant energy source for the body, particularly during periods when food intake is limited, such as during fasting or illness. Without the ability to break down these fats, energy deficits can occur, and harmful intermediate metabolites can accumulate, affecting organs like the liver, heart, and muscles. These disorders can manifest with varying severity, from mild symptoms to life-threatening episodes.
Genetic Inheritance of FAODs
Fatty acid oxidation disorders are inherited conditions. They follow an autosomal recessive inheritance pattern, meaning a child must inherit two copies of a mutated gene, one from each parent, to develop the disorder.
Parents of a child with an FAOD are typically “carriers.” A carrier possesses one normal gene and one mutated gene but usually does not exhibit symptoms because the single working copy of the gene is sufficient. For carrier parents, there is a 25% chance with each pregnancy that their child will inherit two copies of the mutated gene and thus have the disorder. There is also a 50% chance for each child to be an unaffected carrier, and a 25% chance to be unaffected and not a carrier.
Recognizing Symptoms and Triggers
The signs and symptoms of FAODs can vary widely depending on the specific type of disorder and the individual. Many symptoms arise during periods of metabolic stress when the body relies more heavily on fat for energy. Metabolic crisis symptoms often include severe lethargy or extreme sleepiness, recurrent vomiting, and dangerously low blood sugar (hypoglycemia). These episodes can progress to seizures, coma, or even sudden death if untreated.
Muscle-related symptoms are also common, presenting as weakness, pain, and the breakdown of muscle tissue (rhabdomyolysis). This muscle damage can also lead to kidney problems. Additionally, FAODs can affect major organs, with heart problems (e.g., cardiomyopathy, arrhythmias) and liver dysfunction. Some individuals may experience symptoms beginning in infancy, while for others, symptoms might not appear until adolescence or adulthood, often triggered by specific circumstances.
Common triggers for these symptoms include periods of fasting, such as skipping meals or prolonged sleep for infants. Illnesses like a cold or flu, which increase the body’s energy demands and often reduce appetite, can also precipitate a metabolic crisis. Prolonged or strenuous exercise, which depletes sugar stores and shifts the body to fat burning, is another frequent trigger, particularly for muscle-related symptoms in older individuals.
The Diagnostic Process
Identifying fatty acid oxidation disorders often begins with newborn screening programs. This involves a heel prick test performed shortly after birth, usually within the first 24 to 72 hours. Blood samples are collected on a special filter paper and sent to a laboratory to screen for metabolic markers suggestive of an FAOD.
An abnormal newborn screen result does not confirm a diagnosis but indicates the need for further testing. Subsequent diagnostic steps typically involve more specific blood and urine tests. A plasma acylcarnitine profile is a common blood test that can reveal specific patterns of acylcarnitines, which are compounds that accumulate when fatty acid oxidation is impaired, helping to differentiate between various FAODs. Definitive confirmation often comes from genetic testing, which identifies specific gene mutations responsible for the enzyme deficiencies.
Dietary and Medical Management
Managing fatty acid oxidation disorders primarily centers on dietary strategies to ensure a steady supply of usable energy and prevent the buildup of harmful fatty acids. Avoiding fasting periods is a cornerstone of this management. Infants and young children may require frequent feedings and may need bedtime or overnight snacks to prevent long stretches without food. Older children and adults also benefit from regularly scheduled meals and snacks throughout the day. During illness, especially with vomiting or poor appetite, intravenous glucose administration is often necessary to provide immediate energy and prevent metabolic crises.
Dietary composition is also modified to support energy needs. A low-fat, high-carbohydrate diet is often recommended, as carbohydrates provide a readily available energy source that bypasses the impaired fat metabolism pathway. This approach helps maintain stable blood sugar levels and reduces the body’s reliance on fatty acids for fuel. For individuals with long-chain FAODs, a specific fat called medium-chain triglyceride (MCT) oil is frequently used as a supplement. MCTs are metabolized differently than other fats and can be used for energy even when the typical fatty acid oxidation pathway is disrupted.
Medical interventions may also include carnitine supplementation. Carnitine plays a role in transporting fatty acids into mitochondria for energy production. Carnitine levels can become low, and supplementation may help excrete accumulating toxic metabolites. However, carnitine supplementation should only be administered under medical supervision, as its use and dosage depend on the specific disorder and individual needs.