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Genetics Home Reference: your guide to understanding genetic conditions
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Primary carnitine deficiency

Reviewed September 2014

What is primary carnitine deficiency?

Primary carnitine deficiency is a condition that prevents the body from using certain fats for 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.

Signs and symptoms of primary carnitine deficiency typically appear during infancy or early childhood and can include severe brain dysfunction (encephalopathy), a weakened and enlarged heart (cardiomyopathy), confusion, vomiting, muscle weakness, and low blood sugar (hypoglycemia). The severity of this condition varies among affected individuals. Some people with primary carnitine deficiency are asymptomatic, which means they do not have any signs or symptoms of the condition. All individuals with this disorder are at risk for heart failure, liver problems, coma, and sudden death.

Problems related to primary carnitine deficiency can be triggered by periods of fasting or by illnesses such as viral infections. This disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.

How common is primary carnitine deficiency?

The incidence of primary carnitine deficiency in the general population is approximately 1 in 100,000 newborns. In Japan, this disorder affects 1 in every 40,000 newborns.

What genes are related to primary carnitine deficiency?

Mutations in the SLC22A5 gene cause primary carnitine deficiency. This gene provides instructions for making a protein called OCTN2 that transports carnitine into cells. Cells need carnitine to bring certain types of fats (fatty acids) into mitochondria, which are the energy-producing centers within cells. 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.

Mutations in the SLC22A5 gene result in an absent or dysfunctional OCTN2 protein. As a result, there is a shortage (deficiency) of carnitine within cells. Without carnitine, fatty acids cannot enter mitochondria and be used to make energy. Reduced energy production can lead to some of the features of primary carnitine deficiency, such as muscle weakness and hypoglycemia. Fatty acids 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 primary carnitine deficiency.

  • SLC22A5

How do people inherit primary carnitine deficiency?

Primary carnitine deficiency is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive disorder are carriers, which means they each carry one copy of the mutated gene. Carriers of SLC22A5 gene mutations may have some signs and symptoms related to the condition.

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

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

  • Baby's First Test (http://www.babysfirsttest.org/newborn-screening/conditions/carnitine-uptake-defect)
  • Gene Review: Systemic Primary Carnitine Deficiency (http://www.ncbi.nlm.nih.gov/books/NBK84551)
  • Genetic Testing Registry: Renal carnitine transport defect (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0342788)
  • The Linus Pauling Institute: L-Carnitine (http://lpi.oregonstate.edu/infocenter/othernuts/carnitine/)

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

You may find the following resources about primary carnitine 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 primary carnitine deficiency?

  • carnitine transporter deficiency
  • carnitine uptake defect
  • carnitine uptake deficiency
  • CUD
  • renal carnitine transport defect
  • systemic carnitine 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 primary carnitine deficiency?

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

What glossary definitions help with understanding primary carnitine deficiency?

acids ; asymptomatic ; autosomal ; autosomal recessive ; cardiomyopathy ; carnitine ; cell ; coma ; deficiency ; encephalopathy ; fasting ; fatty acids ; gene ; heart failure ; hypoglycemia ; incidence ; inherited ; mitochondria ; newborn screening ; oxidation ; population ; protein ; recessive ; renal ; screening ; syndrome

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

References

  • Amat di San Filippo C, Pasquali M, Longo N. Pharmacological rescue of carnitine transport in primary carnitine deficiency. Hum Mutat. 2006 Jun;27(6):513-23. (http://www.ncbi.nlm.nih.gov/pubmed/16652335?dopt=Abstract)
  • El-Hattab AW, Li FY, Shen J, Powell BR, Bawle EV, Adams DJ, Wahl E, Kobori JA, Graham B, Scaglia F, Wong LJ. Maternal systemic primary carnitine deficiency uncovered by newborn screening: clinical, biochemical, and molecular aspects. Genet Med. 2010 Jan;12(1):19-24. doi: 10.1097/GIM.0b013e3181c5e6f7. (http://www.ncbi.nlm.nih.gov/pubmed/20027113?dopt=Abstract)
  • Lahjouji K, Mitchell GA, Qureshi IA. Carnitine transport by organic cation transporters and systemic carnitine deficiency. Mol Genet Metab. 2001 Aug;73(4):287-97. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11509010?dopt=Abstract)
  • Lamhonwah AM, Olpin SE, Pollitt RJ, Vianey-Saban C, Divry P, Guffon N, Besley GT, Onizuka R, De Meirleir LJ, Cvitanovic-Sojat L, Baric I, Dionisi-Vici C, Fumic K, Maradin M, Tein I. Novel OCTN2 mutations: no genotype-phenotype correlations: early carnitine therapy prevents cardiomyopathy. Am J Med Genet. 2002 Aug 15;111(3):271-84. (http://www.ncbi.nlm.nih.gov/pubmed/12210323?dopt=Abstract)
  • Li FY, El-Hattab AW, Bawle EV, Boles RG, Schmitt ES, Scaglia F, Wong LJ. Molecular spectrum of SLC22A5 (OCTN2) gene mutations detected in 143 subjects evaluated for systemic carnitine deficiency. Hum Mutat. 2010 Aug;31(8):E1632-51. doi: 10.1002/humu.21311. (http://www.ncbi.nlm.nih.gov/pubmed/20574985?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)
  • Magoulas PL, El-Hattab AW. Systemic primary carnitine deficiency: an overview of clinical manifestations, diagnosis, and management. Orphanet J Rare Dis. 2012 Sep 18;7:68. doi: 10.1186/1750-1172-7-68. Review. (http://www.ncbi.nlm.nih.gov/pubmed/22989098?dopt=Abstract)
  • Schimmenti LA, Crombez EA, Schwahn BC, Heese BA, Wood TC, Schroer RJ, Bentler K, Cederbaum S, Sarafoglou K, McCann M, Rinaldo P, Matern D, di San Filippo CA, Pasquali M, Berry SA, Longo N. Expanded newborn screening identifies maternal primary carnitine deficiency. Mol Genet Metab. 2007 Apr;90(4):441-5. Epub 2006 Nov 28. (http://www.ncbi.nlm.nih.gov/pubmed/17126586?dopt=Abstract)
  • Shibbani K, Fahed AC, Al-Shaar L, Arabi M, Nemer G, Bitar F, Majdalani M. Primary carnitine deficiency: novel mutations and insights into the cardiac phenotype. Clin Genet. 2014 Feb;85(2):127-37. doi: 10.1111/cge.12112. Epub 2013 Mar 12. (http://www.ncbi.nlm.nih.gov/pubmed/23379544?dopt=Abstract)
  • Stanley CA. Carnitine deficiency disorders in children. Ann N Y Acad Sci. 2004 Nov;1033:42-51. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15591002?dopt=Abstract)
  • Tein I. Carnitine transport: pathophysiology and metabolism of known molecular defects. J Inherit Metab Dis. 2003;26(2-3):147-69. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12889657?dopt=Abstract)
  • Wang Y, Korman SH, Ye J, Gargus JJ, Gutman A, Taroni F, Garavaglia B, Longo N. Phenotype and genotype variation in primary carnitine deficiency. Genet Med. 2001 Nov-Dec;3(6):387-92. (http://www.ncbi.nlm.nih.gov/pubmed/11715001?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: September 2014
Published: September 29, 2014