Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCADD) is a rare, inherited metabolic disorder that impacts the body’s ability to convert certain fats into energy. Early detection through newborn screening is important as it can prevent serious health complications. Ongoing management is important for individuals diagnosed with MCADD to maintain their health and well-being.
What is Medium Chain Acyl-CoA Dehydrogenase Deficiency?
The human body relies on carbohydrates (broken down into glucose) and fats for energy. During periods when glucose is scarce, such as prolonged fasting, intense exercise, or illness, the body shifts to using stored fats for energy. This process, known as fatty acid oxidation, involves a series of steps that break down fatty acids into smaller units that can be used for fuel.
The medium-chain acyl-CoA dehydrogenase (MCAD) enzyme breaks down medium-chain fatty acids (6 to 12 carbons long). This enzyme is located in the mitochondria, where energy production occurs. When the MCAD enzyme is deficient or not working properly due to a genetic alteration, the body cannot efficiently process these particular fats.
The inability to break down medium-chain fatty acids causes two main problems. First, the body experiences an energy deficit because it cannot access a significant source of fuel, especially when glucose reserves are low. Second, the incompletely broken-down fatty acids and their byproducts, such as octanoylcarnitine (C8), accumulate in tissues. This build-up can become toxic and damage organs like the liver and brain, leading to serious health issues if not addressed.
How MCADD is Identified: Screening and Genetics
MCADD is primarily detected through newborn screening programs (the “heel prick test”). This routine screening is performed shortly after birth, typically around 5 days old, by collecting a few drops of blood from the baby’s heel onto filter paper. The blood sample is analyzed to measure substances like octanoylcarnitine (C8). A high level of C8 suggests that a baby may have MCADD, indicating a “screen positive” result.
A screen positive result does not confirm MCADD but indicates the need for further testing. Confirmatory tests involve additional blood and urine analyses to assess metabolic markers. Genetic testing identifies alterations in the ACADM gene, which produces the MCAD enzyme. This testing can confirm the diagnosis and identify the precise genetic change causing the condition.
MCADD is an autosomal recessive inherited disorder, meaning a child must inherit an altered ACADM gene copy from both parents. If both parents are carriers, each having one altered and one normal gene, they typically do not show symptoms. However, with each pregnancy, there is a 25% chance their child will inherit two altered copies and develop MCADD, a 50% chance the child will be an asymptomatic carrier like their parents, and a 25% chance the child will inherit two normal copies and not have the condition or be a carrier.
Recognizing MCADD: Signs and Potential Risks
If MCADD remains undiagnosed or unmanaged, individuals can experience severe symptoms, especially under metabolic stress. This stress can arise from prolonged fasting, illnesses with fever, or episodes of vomiting or diarrhea. During these times, the body’s demand for energy increases, and its reliance on fat breakdown becomes more pronounced.
Signs of an untreated metabolic crisis in individuals with MCADD include extreme lethargy, persistent vomiting, and dangerously low blood sugar (hypoglycemia). Other indicators include muscle weakness, irritability, and poor feeding in infants. Liver problems, such as an enlarged liver or elevated liver enzymes, can also occur due to the accumulation of byproducts.
Severe complications can occur if a metabolic crisis is not promptly recognized and treated. Complications include seizures, breathing difficulties, and brain damage. In severe instances, an untreated metabolic crisis can lead to a coma or sudden unexpected death, particularly in infants. Understanding these signs and seeking immediate medical attention is important to prevent serious, irreversible harm.
Managing MCADD: Treatment and Lifestyle
Managing MCADD focuses on preventing metabolic crises by ensuring a consistent energy supply and avoiding prolonged fasting. Infants, for example, may require frequent feedings (every 2 to 3 hours) to maintain stable blood glucose levels. As children grow, a bedtime snack and consistent meal schedules become important to prevent overnight fasting from exceeding safe limits (up to 12 hours for older children and adults when well).
Dietary modifications are important for MCADD management. A normal, healthy diet is recommended, including adequate complex carbohydrates (e.g., whole grains, rice, pasta) as a primary energy source. Fat intake may be controlled, typically comprising no more than 30% of total daily calories, to reduce reliance on fat metabolism. Avoiding foods and infant formulas containing medium-chain triglycerides is also advised.
An “emergency plan” is a personalized protocol developed by a metabolic specialist that outlines specific steps to take during periods of illness, vomiting, or other stressors. This plan involves immediately increasing carbohydrate intake, often through glucose-containing solutions like glucose polymer drinks or fruit juices. If an individual cannot tolerate oral intake or if symptoms worsen, immediate medical attention is needed, often requiring intravenous (IV) dextrose administration (at least 10%) in a hospital setting. Lifelong medical supervision by a metabolic specialist and a registered dietitian is important to monitor health, adjust dietary guidelines, and provide ongoing support.