What is medium-chain acyl-CoA dehydrogenase deficiency?

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a rare metabolism disorder that prevents the body from breaking down certain fatty acids and converting them into energy. 

Fatty acids like MCAD are used for energy when children’s bodies run low on sugars (carbohydrates). Sugars commonly run low while sleeping, fasting, during illness or sustained physical activity. 

When a body signals that it needs more energy, organs that depend on a lot of energy (like the brain, heart and muscles) can stop working properly. This can lead to a variety of serious conditions affecting the brain, liver, kidney, heart and other parts of the body.

Without treatment, children born with MCAD deficiency can face sudden death in infancy and serious disabilities throughout life.

MCAD deficiency affects about one in every 15,000 babies born in the United States, and almost exclusively affects people of northwestern European descent.

Causes of MCAD deficiency

MCAD deficiency is a genetic disorder caused by changes in the ACADM gene. The ACADM gene provides instructions to produce an enzyme that breaks down fatty acids and converts them into energy. If the body can’t make enough of this enzyme, the fatty acids can’t be broken down and cannot support the body’s function.

MCAD deficiency is inherited autosomal recessively. That means your child would have to inherit a defective gene from both parents to have this condition.

If a child inherits only one defective gene, they will not have symptoms of the disorder. Instead, they could become carriers of the defective gene and may pass the disorder onto their children.

For children with MCAD deficiency, neither copy of the ACADM gene can provide the proper instructions to produce the enzyme. 

Signs and symptoms of MCAD deficiency

Symptoms of MCAD deficiency can range from mild to severe. On the mild end, some individuals with MCAD deficiency may only have slight exercise intolerance. Children with more severe MCAD deficiency can have significant physical and intellectual disabilities. Severe MCAD deficiency usually appears in infancy. 

Symptoms of MCAD deficiency include:

• Low or no energy
• Low blood sugar (hypoglycemia)
• Muscle weakness and reduced exercise tolerance
• Vomiting

Because infants do not have significant energy storage in their bodies yet, those with MCAD deficiency can quickly become extremely sick (decompensate). 

Certain behaviors by an individual with MCAD deficiency can cause a buildup of toxic substances and low blood sugar (metabolic crisis) such as:

• Missing meals or going too long without eating
• Stomach and digestive problems (such as vomiting or diarrhea) that affect the body’s ability to properly process food 
• Infection or high fever
• Vigorous exercise

Testing and diagnosis for MCAD deficiency

In most cases, MCAD deficiency is discovered during routine newborn screening tests, which are required of all babies born in hospitals in all 50 U.S. states. A simple heel prick is used to get a sample of your baby’s blood and is then sent for testing. This screening is typically completed within a day of the baby’s birth and results are available within weeks. 

Diagnosis of MCAD deficiency is typically established in those who have: 

• Characteristic molecular patterns on plasma acylcarnitine tests and urine organic acid analysis 
• Pathogenic genetic variants identified through genetic sequencing 

Treatment for MCAD deficiency

There is no cure for MCAD deficiency, but it is treatable. Treatment focuses on helping your child maintain normal blood sugar levels by eating regular healthy meals. 

This may include: 

• Eating more often throughout the day, especially during times of increased energy usage
• Avoiding fasting for long periods of time
• Eating a diet high in carbohydrates and low in fat
• Avoiding over-exertion when your child is sick or recovering from sickness or surgery 

If your child experiences severely low blood sugar (also called hypoglycemia), they may need to go to the Emergency Department to receive high-dextrose (sugar) fluids intravenously. 

Treatment also includes avoiding: 

• Foods that include coconut oil, which primarily contain medium-chain fats
• High-fat diets (such as those found in the ketogenic diet)
• Alcohol

All of these can negatively affect a child with MCAD deficiency. 

If left untreated or not treated promptly and properly, MCAD deficiency can lead to brain injury, developmental delays, attention-deficit disorder, muscle weakness, reduced exercise tolerance, irregular heartbeats (cardiac arrhythmia), low blood sugar (hypoglycemia), liver disease, kidney disease and, in rare cases, sudden and unexpected death.

Follow-up care for MCAD deficiency

Patients treated for MCAD deficiency at Children’s Hospital of Philadelphia (CHOP) are followed regularly by the Metabolic Disease Program and followed by subspecialists based on their clinical history.

CHOP is currently conducting clinical trials and researching new therapies for MCAD deficiency. You can see our research studies here. An area that shows great promise is cell and gene therapy.

Cell and gene therapy is an innovative and cutting-edge approach to treating certain genetic disorders like MCAD deficiency. Researchers at CHOP have pioneered some of the first FDA-approved cell and gene therapies for use in children. And we continue to investigate new ways of treating – and potentially curing – genetic disorders in children.

Learn how CHOP is making cell and gene therapy breakthroughs, and which FDA-approved therapies are available at CHOP.