Carnitine palmitoyltransferase I (CPT I) deficiency is a condition that prevents the body from using certain fats for energy, particularly during periods without food (fasting). The severity of this condition varies among affected individuals.

Signs and symptoms of CPT I deficiency often appear during early childhood. Affected individuals usually have low blood glucose (hypoglycemia) and a low level of ketones, which are produced during the breakdown of fats and used for energy. Together these signs are called hypoketotic hypoglycemia. People with CPT I deficiency can also have an enlarged liver (hepatomegaly), liver malfunction, and elevated levels of carnitine in the blood. Carnitine, a natural substance acquired mostly through the diet, is used by cells to process fats and produce energy. Individuals with CPT I deficiency are at risk for nervous system damage, liver failure, seizures, coma, and sudden death.

Problems related to CPT I deficiency can be triggered by periods of fasting or by illnesses such as viral infections. This disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.

Mutations in the CPT1A gene cause CPT I deficiency. This gene provides instructions for making an enzyme called carnitine palmitoyltransferase 1A, which is found in the liver. Carnitine palmitoyltransferase 1A is essential for fatty acid oxidation, which is the multistep process that breaks down (metabolizes) fats and converts them into energy. Fatty acid oxidation takes place within mitochondria, which are the energy-producing centers in cells. A group of fats called long-chain fatty acids cannot enter mitochondria unless they are attached to carnitine. Carnitine palmitoyltransferase 1A connects carnitine to long-chain fatty acids so they can enter mitochondria and be used to produce energy. During periods of fasting, long-chain fatty acids are an important energy source for the liver and other tissues.

Mutations in the CPT1A gene severely reduce or eliminate the activity of carnitine palmitoyltransferase 1A. Without enough of this enzyme, carnitine is not attached to long-chain fatty acids. As a result, these fatty acids cannot enter mitochondria and be converted into energy. Reduced energy production can lead to some of the features of CPT I deficiency, such as hypoketotic hypoglycemia. Fatty acids may also build up in cells and damage the liver, heart, and brain. This abnormal buildup causes the other signs and symptoms of the disorder.

Normal Function

The CPT1A gene provides instructions for making an enzyme called carnitine palmitoyltransferase 1A, which is found in the liver. This enzyme is essential for fatty acid oxidation, a multistep process that breaks down (metabolizes) fats and converts them into energy. Fatty acid oxidation takes place within mitochondria, which are the energy-producing centers in cells. A group of fats called long-chain fatty acids cannot enter mitochondria unless they are attached to a substance known as carnitine. Carnitine palmitoyltransferase 1A connects carnitine to long-chain fatty acids so they can cross the inner membrane of mitochondria. Once these fatty acids are inside mitochondria, carnitine is removed and they can be metabolized to produce energy. During periods of fasting, long-chain fatty acids are an important energy source for the liver and other tissues.

Health Conditions Related to Genetic Changes

Carnitine palmitoyltransferase I deficiency

More than 20 mutations in the CPT1A gene have been found to cause carnitine palmitoyltransferase I (CPT I) deficiency. Most of these mutations change single protein building blocks (amino acids) within carnitine palmitoyltransferase 1A. Mutations in the CPT1A gene severely reduce or eliminate the activity of this enzyme. Without enough of this enzyme, carnitine is not attached to long-chain fatty acids. As a result, these fatty acids cannot enter mitochondria and be converted into energy. Reduced energy production can lead to some of the features of CPT I deficiency, such as low blood glucose (hypoglycemia) and low levels of the products of fat breakdown (hypoketosis). Fatty acids may also build up in cells and damage the liver, heart, and brain. This abnormal buildup causes the other signs and symptoms of the disorder.

Other disorders

CPT1A gene mutations appear to increase the risk of a serious liver disorder that can develop in women during pregnancy. This disorder, called acute fatty liver of pregnancy, begins with abdominal pain and can rapidly progress to liver failure. Signs of acute fatty liver of pregnancy include an abnormal accumulation of fat in the liver, hypoglycemia, increased levels of ammonia in the blood (hyperammonemia), and abnormalities in liver enzymes. A small percentage of women who have a mutation in one copy of the CPT1A gene in each cell and are carrying a fetus with mutations in both copies of the CPT1A gene develop this maternal liver disease. Little is known about the relationship between CPT1A gene mutations and liver problems in the mother during pregnancy.

Other Names for This Gene

• carnitine palmitoyltransferase 1A (liver)
• carnitine palmitoyltransferase I, liver
• CPT1
• CPT1-L
• CPT1A_HUMAN
• L-CPT1

Genomic Location

CPT I deficiency is a genetic condition. Babies inherit it from their biological (birth) parents.

• CPT I deficiency is an autosomal recessive condition. Babies inherit the condition when each parent passes down a nonworking CPT1A gene to their baby. Only babies with two nonworking CPT1A genes—one from the mom and one from the dad—have this condition.
  • People with one working copy and one nonworking copy of the CPT1A gene are called carriers.
  • Carriers do not have or develop the condition. However, they may pass down a nonworking copy of the gene to their children.
  • If two parents are carriers of a nonworking copy of the CPT1A gene, they have a 1 in 4 chance of having a child with CPT I deficiency
  • Carriers for CPT I deficiency often do not know they are carriers before having a child with the condition. In most cases, families have no history of the condition until the birth of a child with CPT I deficiency.
  • Parents who already have a child with CPT I deficiency still have a 1 in 4 chance of having another child with CPT I deficiency. This 1 in 4 chance stays the same for all future children.
• Genetic counselors and medical geneticists can help families learn about this condition and the chance of having children with it.

Signs of CPT I deficiency often appear in early childhood (8 months to 18 months of age). They can be triggered by common illnesses (like a cold or flu) or a long time without food.

Signs of the condition may include the following:

• Poor appetite
• Enlarged liver (hepatomegaly)
• Low blood sugar (hypoglycemia)
• Elevated blood carnitine levels
• Floppy arms and legs (hypotonia)
• Tiredness or lack of energy (lethargy)
• Breathing problems
• Fever
• Diarrhea
• Vomiting
• Seizures
• Behavioral changes

Newborn screening for CPT I deficiency is done using a small amount of blood collected from your baby’s heel. During screening, a special machine measures how much of certain substances (called carnitine and acylcarnitines) are in your baby’s blood. The body produces these substances when it makes energy from fats. Babies with high levels of free carnitine might have CPT I deficiency.

What Happens After an Out-of-Range Screening Result?

If your baby’s blood spot screening result for CPT I deficiency is out-of-range, your baby’s health care provider will contact you. Together, you will discuss next steps and follow-up plans.

An out-of-range screening result does not mean that your baby definitely has the condition. It does mean that your baby needs more follow-up testing.

Your baby may need the following tests after an out-of-range screening result:

• Blood and/or urine tests
• Genetic testing using a blood sample

You should complete any recommended follow-up testing as soon as possible. Babies with this condition can have serious health problems early in childhood if they are not diagnosed and treated quickly.

False-positive newborn screening results for this condition can happen. Some situations can affect screening results for CPT I deficiency:

• Screening samples were collected too early (before the baby is 24 hours old)
• Babies who were given carnitine may have false positive results for this condition.

Newborn screening helps babies lead healthier lives. If your baby has an out-of-range result, follow up with your health care provider quickly. It is important to follow their instructions. Your baby may need to get treatment right away, even if they are not showing signs or symptoms. In some cases, your baby’s health care provider may decide it is best to watch (monitor) your baby to decide next steps. Careful monitoring and early treatment will help your baby stay as healthy as possible.

It is important to talk to your health care provider about which treatment(s) are best for your baby. The goal of treatment is to prevent the health problems caused by this condition.

Treatments may include the following:

• Regular and frequent meals and snacks
• Diet high in carbohydrates and low in fat
• Medium chain triglyceride (MCT) oil supplements to provide fats the body can break down

Children who receive early and ongoing treatment for CPT I deficiency can have healthy growth and development.

CPT I deficiency is a rare disorder; fewer than 50 affected individuals have been identified. This disorder may be more common in the Hutterite and Inuit populations.