Carnitine palmitoyl transferase 1A deficiency

Alternate Names

Carnitine palmitoyltransferase 1A deficiency; CPT1A deficiency; Hepatic CPT1; Hepatic carnitine palmitoyltransferase 1 deficiency; L-CPT 1 deficiency; Carnitine palmitoyl transferase IA deficiency; Hepatic carnitine palmitoyl transferase 1 deficiency; Hepatic carnitine palmitoyl transferase I deficiency; L-CPT1 deficiency; L-CPTI deficiency

Definition

Carnitine palmitoyltransferase I deficiency (CPT1A deficiency) is an inherited metabolic condition that prevents the body from converting certain fats (long-chain fatty acids) into energy, particularly during periods without food. Carnitine, a natural substance acquired mostly through the diet, is required by cells to process fats and produce energy.

Epidemiology

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.

Cause

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.

Inheritance

Autosomal recessive inheritance, a 25% chance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Signs and symptoms

Signs and symptoms of CPT I deficiency often appear during early childhood. Affected individuals usually have low blood sugar (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.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

80%-99% of people have these symptoms

• Behavioral abnormality(Behavioral changes)
• Elevated hepatic transaminase(High liver enzymes)
• Fatigue(Tired)
• Hepatic failure(Liver failure)
• Hypoglycemia(Low blood sugar)
• Muscular hypotonia(Low or weak muscle tone)
• Neurological speech impairment(Speech disorder)
• Reduced tendon reflexes
• Seizure
• Skeletal muscle atrophy(Muscle degeneration)

30%-79% of people have these symptoms

• Coma
• Hemiplegia/hemiparesis(Paralysis or weakness of one side of body)
• Hepatomegaly(Enlarged liver)
• Lethargy
• Loss of consciousness(Passing out)
• Transient hyperlipidemia

5%-29% of people have these symptoms

• Hypertrophic cardiomyopathy(Enlarged and thickened heart muscle)
• Renal tubular acidosis(Accumulation of acid in body due to kidney problem)
• Sudden cardiac death(Premature sudden cardiac death)

Diagnosis

The diagnosis of CPT1A is established in a proband by the detection of biallelic pathogenic variants in CPT1A on molecular genetic testing or diminished carnitine palmitoyltransferase 1 (CPT 1) enzyme activity on cultured skin fibroblasts when molecular genetic testing is not definitive. Residual enzyme activity is 1%-5% in most individuals with CPT1A deficiency.

Treatment

Treatment of CPT1A deficiency usually involves the support of a metabolic specialist and a dietician familiar with CPT1A deficiency. Treatment may differ depending on severity of symptoms and may be lifelong if necessary.

Treatment may include:

• Avoidance prolonged fasting/going a long time without food
• Incorporation of a low-fat, high carbohydrate diet
• Use of medium Chain Triglyceride oil (special type of oil made up of medium chain triglycerides - a type of fatty acid)
• Children with CPT1A deficiency may require additional care during illness to avoid a metabolic crises. Call your healthcare provider should symptoms of an illness occur such as poor appetite, low energy or excessive sleepiness, vomiting, diarrhea, or fever.

NIH genetic and rare disease info

• NIH info on Carnitine palmitoyl transferase 1A deficiency

Carnitine palmitoyl transferase 1A deficiency is a rare disease.

Carnitine palmitoyl transferase 1A deficiency Resources
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