Carnitine palmitoyltransferase I deficiency

Description

Carnitine palmitoyltransferase I (CPT I) deficiency is a condition that prevents the body from using certain fats for energy.

The signs and symptoms of CPT I deficiency are often brought on by episodes of increased energy demands in the body such as illness or periods of fasting. During these times, affected individuals usually develop low levels of glucose in the blood and a low level of ketones, which are normally produced when fats are broken down to be used for energy. Together, these signs are called hypoketotic hypoglycemia. This may cause individuals to experience confusion, seizures, or a lack of energy (lethargy).

People with CPT I deficiency can also develop an enlarged liver (hepatomegaly) that is not able to remove toxins from the blood efficiently. These toxins build up and can affect brain function (hepatic encephalopathy). As long as no brain damage occurs during these episodes of hepatic encephalopathy, individuals with CPT I deficiency often have normal development.

Health can decline quickly in people with CPT I deficiency. Affected individuals are encouraged to avoid prolonged fasting to prevent serious health problems. Individuals with CPT I deficiency are at risk for nervous system damage, liver failure, coma, and sudden death. These problems can begin any time between infancy to adulthood, though some individuals experience no health problems at all.

CPT I deficiency is often detected shortly after birth by newborn screening, which identifies abnormal levels of certain compounds in the blood. People with CPT I deficiency have high levels of a compound called carnitine. Cells use carnitine, a natural substance that is acquired mostly through the diet, to process fats and produce energy.

Frequency

CPT I deficiency is a rare disorder, though its prevalence varies worldwide. It is estimated to occur in 1 in 750,000 to 2,000,000 infants in the United States. CPT I deficiency is more common in certain populations, including some Native Alaskan populations and some Native Pacific Island populations. In certain regions of China, CPT I deficiency is estimated to have an incidence of 1 in 102,388 infants.

Causes

Variants (also caused 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. During periods of fasting, fats are an important energy source for the liver and other tissues. Within liver cells, fatty acid oxidation takes place within mitochondria, which are the energy-producing centers. Before entering mitochondria, a group of fats called long-chain fatty acids must first be attached to carnitine. Carnitine palmitoyltransferase 1A connects carnitine to long-chain fatty acids so they can enter mitochondria and be metabolized to produce energy.

Mitochondria. Credit: U.S. National Library of Medicine.

Variants in the CPT1A gene severely reduce or eliminate the activity of carnitine palmitoyltransferase 1A. As a result, there are not enough enzymes available to attach carnitine to long-chain fatty acids when energy demands are high. Without carnitine, these fatty acids cannot enter mitochondria to be broken down and used for energy. Reduced energy production can lead to some of the features of CPT I deficiency, such as hypoketotic hypoglycemia. Fatty acids and related compounds may also build up in cells and damage the liver, heart, and brain. This abnormal buildup causes the other signs and symptoms of CPT I deficiency.

Conditions that disrupt the metabolism of fatty acids, including CPT I deficiency, are known as fatty acid oxidation disorders.

Inheritance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition. However, women who have one CPT1A gene variant and who are pregnant with a fetus who has two CPT1A gene variants are at risk of developing a condition called acute fatty liver of pregnancy (AFLP). AFLP begins with abdominal pain and can rapidly progress to liver failure.

Autosomal recessive inheritance. Credit: U.S. National Library of Medicine.

Other Names for This Condition

• Carnitine palmitoyltransferase IA deficiency
• CPT 1A deficiency
• CPT deficiency, hepatic, type I
• CPT I deficiency
• Hepatic CPT deficiency
• Hepatic CPT1
• L-CPT1 deficiency
• Liver form of carnitine palmitoyltransferase deficiency
• Nonketotic hypoglycemia

Where this page came from

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