Skip Navigation
Genetics Home Reference: your guide to understanding genetic conditions
http://ghr.nlm.nih.gov/     A service of the U.S. National Library of Medicine®

Carnitine-acylcarnitine translocase deficiency

(often shortened to CACT deficiency)
Reviewed November 2010

What is CACT deficiency?

Carnitine-acylcarnitine translocase (CACT) deficiency is a condition that prevents the body from using certain fats for energy, particularly during periods without food (fasting). Signs and symptoms of this disorder usually begin soon after birth and may include breathing problems, seizures, and an irregular heartbeat (arrhythmia). Affected individuals typically 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 CACT deficiency also usually have excess ammonia in the blood (hyperammonemia), an enlarged liver (hepatomegaly), and a weakened heart muscle (cardiomyopathy).

Many infants with CACT deficiency do not survive the newborn period. Some affected individuals have a less severe form of the condition and do not develop signs and symptoms until early childhood. These individuals are at risk for liver failure, nervous system damage, coma, and sudden death.

How common is CACT deficiency?

CACT deficiency is very rare; at least 30 cases have been reported. 

What genes are related to CACT deficiency?

Mutations in the SLC25A20 gene cause CACT deficiency. This gene provides instructions for making a protein called carnitine-acylcarnitine translocase (CACT). This protein 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, which are the energy-producing centers in cells. A group of fats called long-chain fatty acids must be attached to a substance known as carnitine to enter mitochondria. Once these fatty acids are joined with carnitine, the CACT protein transports them into mitochondria. Fatty acids are a major source of energy for the heart and muscles. During periods of fasting, fatty acids are also an important energy source for the liver and other tissues.

Although mutations in the SLC25A20 gene change the structure of the CACT protein in different ways, they all lead to a shortage (deficiency) of the transporter. Without enough functional CACT protein, long-chain fatty acids cannot be transported into mitochondria. As a result, these fatty acids are not converted to energy. Reduced energy production can lead to some of the features of CACT deficiency, such as hypoketotic hypoglycemia. Fatty acids and long-chain acylcarnitines (fatty acids still attached to carnitine) may also build up in cells and damage the liver, heart, and muscles. This abnormal buildup causes the other signs and symptoms of the disorder.

Related Gene(s)

Changes in this gene are associated with carnitine-acylcarnitine translocase deficiency.

  • SLC25A20

How do people inherit CACT deficiency?

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.

Where can I find information about diagnosis or management of CACT deficiency?

These resources address the diagnosis or management of CACT deficiency and may include treatment providers.

  • Baby's First Test (http://www.babysfirsttest.org/newborn-screening/conditions/carnitine-acylcarnitine-translocase-deficiency)
  • FOD Family Support Group: Diagnostic Approach to Disorders of Fat Oxidation - Information for Clinicians (http://www.fodsupport.org/clinicians.htm)
  • Genetic Testing Registry: Carnitine acylcarnitine translocase deficiency (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0342791)

You might also find information on the diagnosis or management of CACT deficiency in Educational resources (http://www.ghr.nlm.nih.gov/condition/carnitine-acylcarnitine-translocase-deficiency/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/carnitine-acylcarnitine-translocase-deficiency/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about CACT deficiency?

You may find the following resources about CACT deficiency helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for CACT deficiency?

  • carnitine-acylcarnitine carrier deficiency
  • carnitine acylcarnitine translocase deficiency

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about CACT deficiency?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding CACT deficiency?

acids ; ammonia ; arrhythmia ; autosomal ; autosomal recessive ; breakdown ; cardiomyopathy ; carnitine ; carrier ; cell ; coma ; deficiency ; fasting ; fatty acids ; gene ; hyperammonemia ; hypoglycemia ; inherited ; liver failure ; mitochondria ; nervous system ; oxidation ; protein ; recessive

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Costa C, Costa JM, Slama A, Boutron A, Vequaud C, Legrand A, Brivet M. Mutational spectrum and DNA-based prenatal diagnosis in carnitine-acylcarnitine translocase deficiency. Mol Genet Metab. 2003 Jan;78(1):68-73. (http://www.ncbi.nlm.nih.gov/pubmed/12559850?dopt=Abstract)
  • Geven WB, Niezen-Koning KE, Timmer A, van Loon AJ, Wanders RJ, van Spronsen FJ. Pre-eclampsia in a woman whose child suffered from lethal carnitine-acylcarnitine translocase deficiency. BJOG. 2007 Aug;114(8):1028-30. Epub 2007 Jun 18. (http://www.ncbi.nlm.nih.gov/pubmed/17578469?dopt=Abstract)
  • Iacobazzi V, Invernizzi F, Baratta S, Pons R, Chung W, Garavaglia B, Dionisi-Vici C, Ribes A, Parini R, Huertas MD, Roldan S, Lauria G, Palmieri F, Taroni F. Molecular and functional analysis of SLC25A20 mutations causing carnitine-acylcarnitine translocase deficiency. Hum Mutat. 2004 Oct;24(4):312-20. (http://www.ncbi.nlm.nih.gov/pubmed/15365988?dopt=Abstract)
  • Korman SH, Pitt JJ, Boneh A, Dweikat I, Zater M, Meiner V, Gutman A, Brivet M. A novel SLC25A20 splicing mutation in patients of different ethnic origin with neonatally lethal carnitine-acylcarnitine translocase (CACT) deficiency. Mol Genet Metab. 2006 Dec;89(4):332-8. Epub 2006 Aug 17. (http://www.ncbi.nlm.nih.gov/pubmed/16919490?dopt=Abstract)
  • Longo N, Amat di San Filippo C, Pasquali M. Disorders of carnitine transport and the carnitine cycle. Am J Med Genet C Semin Med Genet. 2006 May 15;142C(2):77-85. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16602102?dopt=Abstract)
  • Lopriore E, Gemke RJ, Verhoeven NM, Jakobs C, Wanders RJ, Roeleveld-Versteeg AB, Poll-The BT. Carnitine-acylcarnitine translocase deficiency: phenotype, residual enzyme activity and outcome. Eur J Pediatr. 2001 Feb;160(2):101-4. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11271379?dopt=Abstract)
  • Rubio-Gozalbo ME, Bakker JA, Waterham HR, Wanders RJ. Carnitine-acylcarnitine translocase deficiency, clinical, biochemical and genetic aspects. Mol Aspects Med. 2004 Oct-Dec;25(5-6):521-32. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15363639?dopt=Abstract)
  • Rubio-Gozalbo ME, Vos P, Forget PP, Van Der Meer SB, Wanders RJ, Waterham HR, Bakker JA. Carnitine-acylcarnitine translocase deficiency: case report and review of the literature. Acta Paediatr. 2003 Apr;92(4):501-4. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12801121?dopt=Abstract)
  • Wilcken B. Fatty acid oxidation disorders: outcome and long-term prognosis. J Inherit Metab Dis. 2010 Oct;33(5):501-6. doi: 10.1007/s10545-009-9001-1. Epub 2010 Jan 5. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20049534?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: November 2010
Published: September 1, 2014