VLCAD (Very Long-Chain Acyl-CoA Dehydrogenase) Deficiency

VLCAD (very long-chain acyl-CoA dehydrogenase) deficiency is a rare genetic disorder that prevents your body from breaking down certain fats into energy. It’s a condition that affects your metabolism.

Normally, your body breaks down long-chain fats for fuel. If you have VLCAD, your body doesn’t make enough of a specific enzyme needed for this process. As a result, your body may struggle to produce energy when you need it most. It hits the hardest between meals, during illness and with physical activity. Without careful management, this can lead to:

• Low blood sugar
• Muscle problems
• Liver issues
• Heart disease

Healthcare providers often find VLCAD through routine newborn screening. The results of a blood marker called C14:1 can help your provider estimate how severe VLCAD may be. This will guide them on early treatment decisions to help you manage the condition.

How serious is VLCAD?

The severity of VLCAD varies widely:

• Mild forms may cause few or no symptoms. But you’ll still need to monitor the condition throughout your life.
• Moderate forms may lead to problems during illness or long periods of not eating (fasting).
• Severe forms can affect your muscles, liver, heart and other organs.

Symptoms of VLCAD

Signs and symptoms may appear anytime between infancy and adulthood. Common illnesses (like colds) and fasting can trigger symptoms. But not everyone develops them.

If you do have symptoms, they can vary widely depending on the severity of the condition. Potential VLCAD symptoms may include:

• Low blood sugar
• Extreme tiredness
• Muscle pain and weakness
• Vomiting or poor feeding, especially during illness
• Enlarged liver
• Heart rhythm problems or heart muscle disease

VLCAD deficiency causes

Changes (variants) in the ACADVL gene cause VLCAD deficiency. This gene provides instructions for making very long-chain acyl-CoA dehydrogenase (VLCAD). VLCAD is an enzyme that helps your body break down (metabolize) a type of fat called very long-chain fatty acids. This fat is an important energy source for your muscles, liver and heart.

If the ACADVL gene isn’t working, your body can’t make enough VLCAD. When this happens, your body can’t properly use long-chain fats to make energy. Depending on the amount of working enzyme you have, your symptoms may range from mild to severe.

Risk factors

VLCAD deficiency is an inherited genetic disorder. It’s an autosomal recessive condition. That means both biological parents need to pass on a copy of the nonworking ACADVL gene for the condition to occur. With every pregnancy, there’s a 1 in 4 chance that your child will inherit both nonworking copies and develop the condition. So, the risk factors for VLCAD are:

• Having biological parents who carry ACADVL gene variants
• Having a biological sibling with VLCAD

Genetic counseling can help you understand your risk and options.

How to lower your risk

You can’t change the genetic cause of VLCAD. But you can lower your risk of developing complications by:

• Eating regular meals and snacks
• Avoiding long periods without food
• Following a personalized eating plan
• Seeing your healthcare provider regularly

Complications of this condition

Without proper management, VLCAD can lead to:

• Severe low blood sugar
• Muscle breakdown
• Hospital stays during illness or metabolic stress
• Heart problems
• Liver injury

Early diagnosis and lifelong care can greatly reduce these risks.

How doctors diagnose this condition

Healthcare providers usually find VLCAD through newborn screening. During this routine test, your baby’s provider will look at the levels of C14:1 in their blood.

If your baby’s results are out of the normal range, their provider will follow up with other tests. These can confirm whether your baby has the condition, and if so, how severe it is. These tests may include:

• Blood tests that measure fatty acid markers
• Enzyme activity testing to see how well the VLCAD enzyme works
• Genetic testing of the ACADVL gene
• Heart tests, like echocardiograms or ECGs

Enzyme activity testing is especially helpful to predict how severe VLCAD will be.

How do you treat VLCAD?

VLCAD treatment focuses on preventing energy shortages and avoiding stress on your body. Your healthcare provider will create a personalized treatment plan for you. Based on how severe the condition is, treatment often involves:

• Avoiding fasting
• A specialized, low-fat eating plan
• Medium-chain triglyceride (MCT) supplements
• Triheptanoin (Dojolvi^®), an FDA-approved special fat option you can use under your provider’s supervision
• A plan for what to do when you get sick
• Ongoing monitoring with blood and heart tests

VLCAD foods to avoid

You may need to limit foods high in long-chain fats. Your healthcare provider will explain which foods to avoid. These may include:

• Fatty cuts of meat
• Fried foods
• High-fat dairy products
• Oils rich in long-chain fats

What do people with VLCAD eat?

If you have a milder form of the condition, you may not need strict fat limits. But you’ll still benefit from regular eating habits. Your provider will help you put together a plan. These often include:

• Regular meals and snacks
• Controlled amounts of long-chain fats
• Foods containing medium-chain fats
• Balanced carbohydrates and protein

When should I see my healthcare provider?

Contact your provider if you:

• Aren’t eating well
• Are vomiting
• Have unusual fatigue or muscle pain
• Have dark-colored pee
• Are sick and can’t keep food down

Seek urgent care for signs of low blood sugar, severe weakness or heart-related symptoms.

What is the life expectancy with VLCAD?

Most people with VLCAD have a normal life expectancy with proper management of the condition. This is especially true when the condition is diagnosed early through newborn screening.

For the best long-term outcomes, you’ll need to follow your personalized treatment plan. You’ll also have to see your provider regularly throughout your life.