What are the other Names for this Condition? (Also known as/Synonyms)

• CACT Deficiency Disorder

What is Carnitine-Acylcarnitine Translocase Deficiency Disorder? (Definition/Background Information)

• Carnitine-Acylcarnitine Translocase (CACT) Deficiency Disorder is a disorder that prevents the body from converting certain fats called long-chain fatty acids into energy, particularly during periods without food (fasting)
• 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 role in processing long-chain fatty acids
• There are two forms of Carnitine-Acylcarnitine Translocase Deficiency Disorder. 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 Disorder 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 Disorder 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

(Source: Carnitine-Acylcarnitine Translocase Deficiency; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Carnitine-Acylcarnitine Translocase Deficiency Disorder? (Age and Sex Distribution)

• Carnitine-Acylcarnitine Translocase Deficiency Disorder is a rare congenital disorder. The presentation of symptoms may occur at birth
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Carnitine-Acylcarnitine Translocase Deficiency Disorder? (Predisposing Factors)

• A positive family history may be an important risk factor, since Carnitine-Acylcarnitine Translocase Deficiency Disorder can be inherited
• Currently, no risk factors have been clearly identified for this deficiency disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Carnitine-Acylcarnitine Translocase Deficiency Disorder? (Etiology)

• Carnitine-Acylcarnitine Translocase Deficiency Disorder 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 blood
• Carnitine-Acylcarnitine Translocase (CACT) Deficiency Disorder is inherited in an autosomal recessive pattern

(Source: Carnitine-Acylcarnitine Translocase Deficiency Disorder; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

What are the Signs and Symptoms of Carnitine-Acylcarnitine Translocase Deficiency Disorder?

The signs and symptoms of Carnitine-Acylcarnitine Translocase Deficiency Disorder may include:

• Atrioventricular block
• Bradycardia
• Cardiorespiratory arrest
• Elevated serum creatine phosphokinase
• Generalized hypotonia
• Hypoglycemia
• Ventricular extrasystoles
• Ventricular hypertrophy

Very frequently present symptoms in 80-99% of the cases:

• Abnormality of skeletal muscles
• Cardiomyopathy
• Decreased plasma carnitine
• Dicarboxylic aciduria
• Elevated creatine kinase after exercise
• Elevated hepatic transaminases
• Elevated plasma acylcarnitine levels
• Encephalopathy
• Fasting hypoglycemia
• Hepatomegaly
• Hyperammonemia
• Hypoketotic hypoglycemia
• Hypotension
• Irritability
• Lethargy
• Respiratory insufficiency
• Rhabdomyolysis
• Ventricular tachycardia

Frequently present symptoms in 30-79% of the cases: Coma

Occasionally present symptoms in 5-29% of the cases:

• Cyanosis
• Hepatic failure
• Hypothermia
• Microcephaly
• Nystagmus
• Oliguria
• Preeclampsia
• Seizures
• Sudden episodic apnea

(Source: Carnitine-Acylcarnitine Translocase Deficiency; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Carnitine-Acylcarnitine Translocase Deficiency Disorder Diagnosed?

• Genetic testing for Carnitine-Acylcarnitine Translocase Deficiency Disorder 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 CACT Deficiency Disorder, however, it can be helpful for carrier testing or prenatal diagnosis

(Source: Carnitine-Acylcarnitine Translocase Deficiency; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Carnitine-Acylcarnitine Translocase Deficiency Disorder?

The complications of Carnitine-Acylcarnitine Translocase Deficiency Disorder may include:

• Heart abnormalities
• Liver dysfunction

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Carnitine-Acylcarnitine Translocase Deficiency Disorder Treated?

The treatment for Carnitine-Acylcarnitine Translocase Deficiency Disorder includes:

• Strict avoidance of fasting: Infants and young children with CACT Deficiency Disorder 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 Disorder
• 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 Disorder 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

(Source: Carnitine-Acylcarnitine Translocase Deficiency Disorder; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How can Carnitine-Acylcarnitine Translocase Deficiency Disorder be Prevented?

• Currently, Carnitine-Acylcarnitine Translocase Deficiency Disorder may not be preventable, since it is a genetic disorder
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders
• Regular medical screening at periodic intervals with tests and physical examinations are recommended

What is the Prognosis of Carnitine-Acylcarnitine Translocase Deficiency Disorder? (Outcomes/Resolutions) 

• Prompt and careful treatment may help prevent or control symptoms in children with mild Carnitine-Acylcarnitine Translocase Deficiency Disorder
• 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

(Source: Carnitine-Acylcarnitine Translocase Deficiency Disorder; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Additional and Relevant Useful Information for Carnitine-Acylcarnitine Translocase Deficiency Disorder:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/