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.

To better understand these concepts, you may benefit from visiting the Elmhurst College website which offers a virtual animation that explains how fatty acids are transferred from the cytoplasm to the mitochondria.

Genetic testing for carnitine-acylcarnitine translocase deficiency can be done on a blood sample. Genetic testing, also called DNA testing, looks for changes in the pair of genes that cause carnitine- acylcarnitine translocase deficiency. In some affected children, both gene changes can be found. However, in other children, neither or only one of the two gene changes can be found, even though we know they are present. DNA testing is not necessary to diagnose carnitine-acylcarnitine translocase deficiency, however, it can be helpful for carrier testing or prenatal diagnosis.

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

Prompt and careful treatment may help prevent or control symptoms in children with mild carnitine-acylcarnitine translocase deficiency.[321 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 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.

The Screening, Technology, and Research in Genetics (STAR-G) Project was a multi-state collaborative effort to obtain research data, identify strategies, and develop written materials for addressing the financial, ethical, legal and social issues surrounding the use of tandem mass spectrometry for newborn screening. As part of the STAR-G Project, fact sheets on newborn screening disorders have been developed for parents. To view the fact sheet on carnitine acylcarnitine translocase deficiency (CAT), visit the STAR-G link.

The Newborn Screening Coding and Terminology Guide has information on the standard codes used for newborn screening tests. Using these standards helps compare data across different laboratories. This resource was created by the National Library of Medicine.