Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCAD)

Medium-chain acyl-CoA dehydrogenase deficiency, or MCAD, is a genetic condition that affects how your body turns fat into energy. When you go without food for several hours, your body normally breaks down stored fat to keep blood sugar levels stable. People with MCAD deficiency cannot break down certain types of fats called medium-chain fatty acids. This means their bodies struggle to produce energy during periods of fasting or illness.

MCAD is the most common fatty acid oxidation disorder, affecting about 1 in 10,000 to 20,000 people. It is inherited in an autosomal recessive pattern. This means both parents must carry a gene mutation for a child to develop the condition. Most people with MCAD deficiency are diagnosed through newborn screening. However, some cases go undetected until a metabolic crisis occurs in childhood or even adulthood.

The condition causes a problem called hypoketotic hypoglycemia. This means dangerously low blood sugar without the normal production of ketones. Ketones are chemicals your body makes when it breaks down fat for energy. In healthy people, ketones rise during fasting to fuel the brain and muscles. In MCAD deficiency, the body cannot make enough ketones. This leaves the brain without its backup fuel source during times of low blood sugar.

• Low blood sugar, especially after fasting or during illness
• Extreme tiredness and weakness
• Vomiting and nausea
• Confusion or altered mental state
• Seizures in severe cases
• Loss of consciousness or coma if untreated
• Liver enlargement during metabolic crisis
• Lethargy and difficulty waking up
• Poor feeding in infants
• Muscle weakness and low muscle tone

Many people with MCAD deficiency have no symptoms between episodes. Symptoms typically appear only during fasting, illness, or times of increased energy demand. Some individuals may go years without experiencing a metabolic crisis if they eat regularly. Early diagnosis through newborn screening helps prevent the first crisis from occurring.

MCAD deficiency is caused by mutations in the ACADM gene. This gene provides instructions for making an enzyme that breaks down medium-chain fatty acids. When the enzyme does not work properly, these fatty acids build up in the body. At the same time, the body cannot produce enough energy or ketones during fasting. The condition is inherited when both parents pass on a mutated copy of the gene. Carriers with only one mutated gene do not develop symptoms.

Metabolic crises are typically triggered by situations that increase energy demands or reduce food intake. Common triggers include viral infections, stomach bugs that cause vomiting, prolonged fasting, and strenuous exercise without adequate food. Infants are at higher risk because they have limited energy stores and may sleep through feedings. Young children face increased risk during growth spurts or when dealing with common childhood illnesses. Adults with undiagnosed MCAD may experience their first crisis during pregnancy, surgery, or severe illness.

MCAD deficiency is typically diagnosed through newborn screening programs in most states. The screening test uses a blood sample to measure acylcarnitine levels, which are elevated in MCAD deficiency. If the newborn screen is positive, confirmatory testing includes genetic testing to identify ACADM gene mutations. Additional tests may include plasma acylcarnitine profile and urine organic acid analysis. A key finding is inappropriately low or absent urine ketones during an episode of low blood sugar.

Rite Aid's testing service includes urine ketone testing as part of our flagship panel. This can help monitor metabolic status in people already diagnosed with MCAD deficiency. Low urine ketones in the context of fasting or illness symptoms may indicate poor fat metabolism. Regular monitoring helps you and your doctor track your metabolic health. Get tested at over 2,000 Quest Diagnostics locations nationwide with our subscription service.

• Avoid prolonged fasting by eating regular meals and snacks every 4 to 6 hours
• Infants may need feeding every 2 to 4 hours, even overnight
• During illness, consume frequent carbohydrate-rich foods and drinks to maintain blood sugar
• Carry emergency glucose sources like juice or glucose tablets
• Seek immediate medical care during vomiting illness or inability to eat
• Emergency treatment with intravenous glucose during metabolic crises
• L-carnitine supplementation may be recommended by some doctors
• Avoid medium-chain triglyceride oils and supplements
• Work with a metabolic dietitian to create a safe eating plan
• Wear medical alert identification at all times