Carnitine-acylcarnitine translocase deficiency

Congenital and Genetic Diseases, Newborn Screening, Heart Diseases, Metabolic disorders


Carnitine-acylcarnitine translocase (CACT) deficiency is a disease that prevents the body from converting certain fats called long-chain fatty acids into energy, particularly during periods without food (fasting). Ultimately this prevents certain fats (long-chain acylcarnitine) being converted to energy and results in a build up of the fat which is harmful to body organs and tissues. Carnitine, a natural substance acquired mostly through the diet, is used by cells to process fats and produce energy. People with this disorder have a faulty transporter (CACT) that disrupts carnitine's role in processing long-chain fatty acids.

There are two forms of carnitine-acylcarnitine translocase deficiency. The most common type is severe and happens in newborns. A milder, less common type happens in older infants and children. Most patients with CACT deficiency have a severe disease presenting within the first 48 hours of life as low blood sugar with ketonic bodies (hypoketotic hypoglycemia), high ammonia (hyperammonemia) levels in the blood, increased heart muscle (cardiomyopathy), and abnormal heart rhythm (arrhythmias), as well as skeletal muscle damage, liver problems, and low temperature (hypothermia). Neurological involvement, seizures, and developmental delay are also present. Rarely, patients present as a sudden infant death. The CACT deficiency is caused by mutations in the SLC25A20 gene. Treatment is done by avoiding fasting and having a low long-chain fat diet with medium chain triglyceride (MCT) supplementation.

Symptoms - Carnitine-acylcarnitine translocase deficiency

The signs of carnitine-acylcarnitine translocase (CACT) deficiency usually begin within the first few hours after birth. Seizures, an irregular heartbeat (arrhythmia), and breathing problems are often the first signs of the deficiency. It may also present with extremely low level of ketones (which are products of fat breakdown that are used for energy) and with low blood sugar (hypoglycemia). Together these signs are called "hypoketotic hypoglycemia", which can result in unconsciousness and seizures.

Other signs that are often present include:

  • Excess ammonia in the blood (hyperammonemia)
  • Enlarged liver (hepatomegaly)
  • Heart abnormalities (cardiomyopathy) and abnormal heart rhythm (arrhythmias)
  • Muscle weakness
  • Neurological problems
  • Seizures
  • Developmental delay

In some severe cases of CACT deficiency, infants may present with sudden infant death.

Children with the mild type of CACT deficiency usually start having symptoms before age three and present with episodes of hypoketotic hypoglycemia and hyperammonemia often brought on by fasting and/or by being sick.

Other Synptoms

  • Hypoglycemia
  • Vomiting
  • Gastroesophageal reflux
  • Chronic mild blood ammonia level elevation
  • Severe skeletal myopathy
  • Mild hypertrophic cardiomyopathy
  • Ventricular dysrhythmias
  • Seizures
  • Breathing problems
  • Low ketone level
  • Unconsciousness
  • Enlarged liver
  • Muscle weakness

Causes - Carnitine-acylcarnitine translocase deficiency

Carnitine-acylcarnitine translocase deficiency is caused by mutations in the SLC25A20 gene, which provides instructions for making an enzyme called carnitine-acylcarnitine translocase (CACT), which 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. A group of fats called long-chain fatty acids must be attached to a substance known as carnitine to enter the mitochondria. CACT's job is to transport them into the mitochondria. CACT also helps to break down fat already stored in the body.

Energy from fat keeps us going whenever our bodies run low of their main source of energy, a type of sugar called glucose. Our bodies rely on fat for energy when we do not eat for a stretch of time - like when we miss a meal or when we sleep.
The mutations result in missed or non-functional CACT (CACT deficiency).When the CACT normal enzyme is missing or not working well, the body cannot use fat for energy, and must rely solely on glucose. Although glucose is a good source of energy, there is a limited amount available in the body. Once the glucose has been used up, the body tries to use fat without success. This leads to low blood sugar, called hypoglycemia, and to the buildup of harmful substances in the blood

Carnitine-acylcarnitine translocase (CACT) deficiency is inherited in an autosomal recessive pattern.

Prevention - Carnitine-acylcarnitine translocase deficiency

Not supplied.

Diagnosis - Carnitine-acylcarnitine translocase deficiency

Not supplied.

Prognosis - Carnitine-acylcarnitine translocase deficiency

Prompt and careful treatment may help prevent or control symptoms in children with mild carnitine-acylcarnitine translocase deficiency. Outcomes seem to correlate better with the absence of cardiac disease. Diagnosis before the occurrence of clinical symptoms and very early treatment, together with good dietary compliance, could lead to a better prognosis, especially in milder clinical cases. However, some children continue to have metabolic crises and other health problems despite treatment. Even with treatment, there is a risk of death, especially in newborns with symptoms.

Treatment - Carnitine-acylcarnitine translocase deficiency

Treatment includes:

  • Strict avoidance of fasting: Infants and young children with carnitine-acylcarnitine translocase (CACT) deficiency need to eat frequently to prevent a metabolic crisis. In general, it is often suggested that infants be fed every four to six hours, although some babies need to eat even more frequently than this (every 3 hours). It is important that infants be fed during the night. They may need to be woken up to eat if they do not wake up on their own.
  • A low long-chain fat diet and medium-chain triglycerides (MCT) supplementation: The MCT formula should be as low as possible in C10 and C12 fatty acids because high dietary intake of these can lead to a metabolic crisis. Medium Chain Triglyceride oil (MCT oil) is sometimes used as part of the food plan for people with CACT deficiency.
  • Administration of a high carbohydrate diet: Carbohydrates give the body many types of sugar that can be used as energy. In fact, for children needing this treatment, most food in the diet should be carbohydrates (bread, pasta, fruit, vegetables, etc.) and protein (lean meat and low-fat dairy food).
  • Supplementation with L-carnitin: A safe and natural substance that helps body cells make energy and get rid of harmful wastes. However, its benefits are not yet determined.
  • Administration of intravenous glucose: In cases of hypoglycemia, hyperammonemia, and for the prevention of lipolysis (the breakdown of fat stored in fat cells) in the newborn, which may be lifesaving.
  • Other treatment options for milder cases with some residual CACT activity may be the administration of statins and fibrates that have been shown to increase the amount of CACT.

When children get sick, parents should call the doctor. Children with CACT deficiency need to eat extra starchy food and drink more fluids during any illness (even if they may not feel hungry) or they could develop a metabolic crisis.

Resources - Carnitine-acylcarnitine translocase deficiency

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