What are long-chain fatty acid oxidation disorders (LC-FAODs)?

Long-chain fatty acid oxidation disorders (LC-FAODs) are a group of rare metabolic disorders that prevent the body from breaking down long-chain fatty acids and converting them to energy. 

Our bodies break down sugars (carbohydrates) first to give us energy. When sugars run low, our body switches to burning fat. So when your child’s body runs low on sugars (for example, while they’re sleeping, fasting, feeling sick or exercising), their bodies will try to break down long-chain fatty acids (LCFAs) to use for energy. 

But children with LC-FAOD can’t break these fatty acids down. This means that organs that depend on a lot of energy – such as the brain, heart and muscles – may stop working properly. This can lead to a variety of serious conditions affecting the brain, liver, kidney, heart and other parts of the body.

If LC-FAOD is left untreated, it can lead to life-threatening low blood sugar (hypoglycemia), heart disease, breakdown of muscle tissue (rhabdomyolysis) and high levels of ammonia in the body (hyperammonemia), which can cause damage to the liver and brain.

Specific LC-FAODs include deficiencies of:

• Very long-chain acyl-CoA dehydrogenase (VLCAD)
• Carnitine palmitoyltransferase I (CPT I)
• Carnitine palmitoyltransferase II (CPT II)
• Long-chain 3-hydroxy-acyl-CoA dehydrogenase (LCHAD) deficiency/Trifunctional protein (TFP) 

Causes of long-chain fatty acid oxidation disorders

LC-FAODs are genetic disorders caused by changes in one of several genes involved in LCFA oxidation. These genes provide instructions to produce the enzymes that break down long-chain fatty acids and convert them to energy. If your child’s body can’t make enough of one of these enzymes, the LCFAs can’t be used for energy, and symptoms of LC-FAOD develop.

LC-FAODs are inherited autosomal recessively. That means your child would have to inherit a defective gene from both parents to have this condition. 

If the altered gene comes from only one parent, your child will not develop the disorder themselves. But they could become a carrier and may pass the altered gene on to their children. 

The specific genes responsible for these conditions are:

• Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency – ACADVL
• Carnitine palmitoyltransferase I (CPT I) deficiency – CPT1
• Carnitine palmitoyltransferase II (CPT II) deficiency – CPT2
• Long-chain 3-hydroxy-acyl-CoA dehydrogenase (LCHAD) deficiency/Trifunctional protein (TFP) deficiency – HADHA, HADHB

Signs and symptoms of long-chain fatty acid oxidation disorders 

Symptoms of LC-FAODs may vary depending on your child’s specific deficiency. In general, symptoms begin in infancy and early childhood. But if the disorder progresses slowly, symptoms may not appear until adolescence or adulthood. Symptoms typically become visible during periods of physical stress such as fever, illness or going long periods without eating.

People with mild forms of LC-FAODs may have exercise intolerance and muscle pain and weakness that can begin as late as adulthood. More severe symptoms of LC-FAODs can include:

• Low blood sugar levels (hypoglycemia)
• Heart disease (cardiomyopathy) or abnormal heart rhythm (arrhythmia)
• Liver disease
• Rhabdomyolysis (muscle breakdown)
• Hyperammonemia (high ammonia levels)
• Speech and motor developmental delays

Testing and diagnosis for long-chain fatty acid oxidation disorders

Newborn screening tests, which are required for all babies born in hospitals across all 50 U.S. states, will usually identify those affected with LC-FAODs. A simple heel prick is used to get a sample of your baby’s blood and is then sent for testing. For those who are identified during screening, or who show symptoms, a blood plasma test and/or genetic testing can confirm the diagnosis. 

Treatment for long-chain fatty acid oxidation disorders

LC-FAODs have no cure, but they can be treated. The most important treatment is to help your child maintain healthy blood sugar levels through diet changes. These changes include:

• Eating frequent meals and avoiding fasting to prevent low blood sugar 
• Restricting fat 
• Eating more high-carbohydrate foods during times of illness, exercise or increased energy usage 
• Adding in medium-chain fats such as MCT oil as a supplement
• Taking the medication triheptanoin (Dojolvi^®), a triglyceride that supplements your child’s diet with calories and fatty acids for energy

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

Follow-up care 

Patients treated for LC-FAODs at Children’s Hospital of Philadelphia (CHOP) are monitored regularly at the Metabolic Disease Program, and followed by other subspecialists based on their clinical history, such as developmental therapy and cardiology. 

CHOP is currently conducting clinical trials and researching new therapies for LC-FAODs. 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 LC-FAODs. 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.