Rare Oncology News

Disease Profile

Carnitine-acylcarnitine translocase deficiency

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Infancy

ageofonset-infancy.svg

ICD-10

E71.3

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

no.svg

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

rnn-autosomalrecessive.svg

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

no.svg

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

no.svg

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

no.svg

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

no.svg

Not applicable

no.svg

Categories

Congenital and Genetic Diseases; Heart Diseases; Metabolic disorders;

Summary

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). 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.[1]

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.[2] 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.[3][4] 

Carnitine-acylcarnitine translocase deficiency is a type of fatty acid oxidation disorder.

Symptoms

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.[1]

Other signs that are often present include:[1][4]

  • 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.[1]

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.[2]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Cardiomyopathy
Disease of the heart muscle
0001638
Decreased plasma carnitine
0003234
Dicarboxylic aciduria
0003215
Elevated creatine kinase after exercise
0008331
Elevated hepatic transaminase
High liver enzymes
0002910
Elevated plasma acylcarnitine levels
0045045
Encephalopathy
0001298
Fasting hypoglycemia
Low blood sugar when fasting
0003162
Global developmental delay
0001263
Hepatomegaly
Enlarged liver
0002240
Hyperammonemia
High blood ammonia levels
0001987
Hypoketotic hypoglycemia
0001985
Hypotension
Low blood pressure
0002615
Irritability
Irritable
0000737
Lethargy
0001254
Muscle weakness
Muscular weakness
0001324
Respiratory insufficiency
Respiratory impairment
0002093
Rhabdomyolysis
Breakdown of skeletal muscle
0003201
Ventricular tachycardia
0004756
5%-29% of people have these symptoms
Coma
0001259
Cyanosis
Blue discoloration of the skin
0000961
Hepatic failure
Liver failure
0001399
Hypothermia
Abnormally low body temperature
0002045
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

0000252
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Oliguria
0100520
Preeclampsia
0100602
Seizure
0001250
Sudden episodic apnea
0002882
Percent of people who have these symptoms is not available through HPO
Atrioventricular block
Interruption of electrical communication between upper and lower chambers of heart
0001678
Autosomal recessive inheritance
0000007
Bradycardia
Slow heartbeats
0001662
Cardiorespiratory arrest
0006543
Elevated serum creatine kinase
Elevated blood creatine phosphokinase
Elevated circulating creatine phosphokinase
Elevated creatine kinase
Elevated serum CPK
Elevated serum creatine phosphokinase
High serum creatine kinase
Increased CPK
Increased creatine kinase
Increased creatine phosphokinase
Increased serum CK
Increased serum creatine kinase
Increased serum creatine phosphokinase

[ more ]

0003236
Generalized hypotonia
Decreased muscle tone
Low muscle tone

[ more ]

0001290
Hypoglycemia
Low blood sugar
0001943
Ventricular extrasystoles
Extra heart beat
0006682
Ventricular hypertrophy
0001714

Cause

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.[2][5]

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.[2]

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.[2]

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.

Diagnosis

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.[2]

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Newborn Screening

    • An ACTion (ACT) sheet is available for this condition that describes the short-term actions a health professional should follow when an infant has a positive newborn screening result. ACT sheets were developed by experts in collaboration with the American College of Medical Genetics.
    • An Algorithm flowchart is available for this condition for determining the final diagnosis in an infant with a positive newborn screening result. Algorithms are developed by experts in collaboration with the American College of Medical Genetics.
    • Baby's First Test is the nation's newborn screening education center for families and providers. This site provides information and resources about screening at the local, state, and national levels and serves as the Clearinghouse for newborn screening information.
    • 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.
    • National Newborn Screening and Global Resource Center (NNSGRC) provides information and resources in the area of newborn screening and genetics to benefit health professionals, the public health community, consumers and government officials.

      Treatment

      Treatment includes:[2][6][4]

      • 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 hypoglycemiahyperammonemia, 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.[4]

      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.[2]

      Management Guidelines

      • Orphanet Emergency Guidelines is an article which is expert-authored and peer-reviewed that is intended to guide health care professionals in emergency situations involving this condition.

        Organizations

        Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

        Organizations Supporting this Disease

          Organizations Providing General Support

            Learn more

            These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

            Where to Start

            • Genetics Home Reference (GHR) contains information on Carnitine-acylcarnitine translocase deficiency. This website is maintained by the National Library of Medicine.
            • The Screening, Technology And Research in Genetics (STAR-G) Project has a fact sheet on this condition, which was written specifically for families that have received a diagnosis as a result of newborn screening. This fact sheet provides general information about the condition and answers questions that are of particular concern to parents.

              In-Depth Information

              • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
              • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
              • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
              • PubMed is a searchable database of medical literature and lists journal articles that discuss Carnitine-acylcarnitine translocase deficiency. Click on the link to view a sample search on this topic.

                References

                1. Carnitine-acylcarnitine translocase deficiency. Genetics Home Reference. November, 2015; https://ghr.nlm.nih.gov/condition=carnitineacylcarnitinetranslocasedeficiency.
                2. Carnitine-acylcarnitine translocase deficiency. Screening, Technology and Research in Genetics. 2016; https://www.newbornscreening.info/Parents/fattyaciddisorders/CAT.html.
                3. Vitoria I, Martín-Hernández E, Peña-Quintana L, et al. Carnitine-Acylcarnitine Translocase Deficiency: Experience with Four Cases in Spain and Review of the Literature. JIMD Reports. 2015; 20:11-20. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375124/.
                4. Carnitine-acylcarnitine translocase deficiency. Orphanet. 2014; https://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=3343.
                5. SLC25A20 gene. Genetics Home Reference. 2017; https://ghr.nlm.nih.gov/gene/SLC25A20.
                6. Copeland S, Tuerck J, Paradise L. Carnitine-Acylcarnitine Translocase Deficiency. Oregon Department of Human Services Newborn Screening. https://www.oregon.gov/DHS/ph/nbs/docs/carnitinetranslocase.pdf. Accessed 4/4/2008.

                Rare Oncology News