Long-chain acyl-CoA dehydrogenase deficiency (LCADD) is a rare inherited metabolic disorder. Individuals with LCADD cannot properly process long-chain fatty acids, which serve as a significant energy source, especially when the body relies on fat stores. This deficiency can lead to serious health complications if not managed appropriately.
Understanding Long-Chain Acyl-CoA Dehydrogenase Deficiency
LCADD results from a problem with the long-chain acyl-CoA dehydrogenase (LCAD) enzyme. This enzyme plays a role in the mitochondrial fatty acid oxidation pathway, a process where the body breaks down long-chain fatty acids for energy. When the LCAD enzyme is deficient or not functioning correctly, these fatty acids cannot be properly metabolized.
Instead, unprocessed long-chain fatty acids and their byproducts accumulate, becoming toxic to various tissues. The body is then unable to produce sufficient energy from fats, particularly during times of increased energy demand, such as fasting or illness. LCADD is an autosomal recessive condition, meaning an individual must inherit a non-working copy of the responsible gene, ACADVL, from each parent to develop the disorder.
Recognizing the Symptoms
The symptoms of LCADD can vary widely in their presentation and severity. Common signs include low blood sugar (hypoglycemia), which occurs because the body cannot access fat stores for energy. Muscle weakness and intolerance to physical activity are also frequently observed, sometimes progressing to rhabdomyolysis, a condition involving muscle breakdown.
Heart muscle weakness, known as cardiomyopathy, and liver problems, such as an enlarged liver, can also develop. In severe cases, particularly if untreated during a metabolic crisis, individuals may experience seizures or even fall into a coma. Symptoms often become apparent during infancy or early childhood, typically triggered by periods of fasting, illness, or increased energy requirements.
Diagnosis and Screening
Diagnosing LCADD often begins with newborn screening programs. These programs commonly use tandem mass spectrometry to detect specific metabolic markers in a dried blood spot from a heel prick. Early detection through newborn screening has significantly improved outcomes for affected infants.
If the newborn screen suggests LCADD, confirmatory tests are performed. Genetic testing can identify mutations in the ACADVL gene, providing a definitive diagnosis. Additionally, enzyme activity assays measure the level of LCAD enzyme activity to confirm the deficiency.
Managing the Condition
Managing LCADD primarily involves dietary modifications to prevent metabolic crises. Avoiding prolonged fasting is essential; frequent feedings ensure a continuous energy supply. A diet low in long-chain fats is prescribed, reducing the intake of fats the body struggles to process.
Medium-chain triglyceride (MCT) oil supplementation is a common strategy, as MCTs are absorbed and metabolized differently, providing an alternative energy source that bypasses the affected pathway. L-carnitine supplementation may also be used to help transport fatty acids.
During periods of illness or other metabolic stress, prompt intervention is necessary to prevent severe complications. Emergency protocols involve the intravenous administration of glucose to provide immediate energy and prevent hypoglycemia. Close monitoring by a metabolic specialist and adherence to individualized dietary plans are ongoing aspects of care.
Living with LCADD: Long-Term Outlook
With early diagnosis and consistent adherence to management strategies, individuals with LCADD can lead healthy and productive lives. Strict adherence to dietary guidelines and fasting avoidance significantly reduces the risk of severe complications such as cardiomyopathy or rhabdomyolysis. Ongoing medical supervision is necessary throughout life to adjust management plans as needed and monitor for any potential issues. If the condition is not well-managed, there is a greater risk of recurrent metabolic crises and long-term health problems.