Primary carnitine deficiency

Title

Other Names:

Systemic primary carnitine deficiency; Carnitine uptake defect; Carnitine deficiency, systemic, due to defect in renal reabsorption of carnitine; Systemic primary carnitine deficiency; Carnitine uptake defect; Carnitine deficiency, systemic, due to defect in renal reabsorption of carnitine; Carnitine plasma-membrane transporter deficiency; Carnitine transporter deficiency; Carnitine uptake deficiency See More

Categories:

Congenital and Genetic Diseases; Heart Diseases; Metabolic disorders; Congenital and Genetic Diseases; Heart Diseases; Metabolic disorders; Nervous System Diseases; Newborn Screening See More

Summary Summary

Primary carnitine deficiency is a genetic condition that prevents the body from using certain fats for energy, particularly during periods without food (fasting). The nature and severity of signs and symptoms may vary, but they most often appear during infancy or early childhood and can include severe brain dysfunction (encephalopathy), cardiomyopathy, confusion, vomiting, muscle weakness, and hypoglycemia.^[1] Some individuals may only have fatigability in adulthood, or no symptoms at all. This condition is caused by mutations in the SLC22A5 gene and is inherited in an autosomal recessive manner. Treatment and prevention of symptoms typically includes oral L-carnitine supplementation.^[2]

Last updated: 7/9/2012

Symptoms Symptoms

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.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Acute encephalopathy		0006846
Bilateral tonic-clonic seizure with focal onset		0007334
Clumsiness		0002312
Confusion	Disorientation Easily confused Mental disorientation [ more ]	0001289
Elevated hepatic transaminase	High liver enzymes	0002910
Hepatomegaly	Enlarged liver	0002240
Neck muscle weakness	Floppy neck	0000467
Vomiting	Throwing up	0002013
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance		0000007
Cardiomegaly	Enlarged heart Increased heart size [ more ]	0001640
Coma		0001259
Congestive heart failure	Cardiac failure Cardiac failures Heart failure [ more ]	0001635
Decreased carnitine level in liver		0045061
Decreased plasma carnitine		0003234
Encephalopathy		0001298
Endocardial fibroelastosis		0001706
Excessive daytime somnolence	Excessive daytime sleepiness More than typical sleepiness during day [ more ]	0001262
Failure to thrive	Faltering weight Weight faltering [ more ]	0001508
Generalized hypotonia	Decreased muscle tone Low muscle tone [ more ]	0001290
Hepatic steatosis	Fatty infiltration of liver Fatty liver [ more ]	0001397
Hyperammonemia	High blood ammonia levels	0001987
Hypertrophic cardiomyopathy	Enlarged and thickened heart muscle	0001639
Hypoglycemia	Low blood sugar	0001943
Impaired gluconeogenesis		0005959
Lethargy		0001254
Muscular hypotonia	Low or weak muscle tone	0001252
Myopathy	Muscle tissue disease	0003198
Recurrent hypoglycemia	Recurrent low blood sugar levels	0001988
Reduced muscle carnitine level		0030362

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 9/1/2020

Do you have updated information on this disease? We want to hear from you.

Cause Cause

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. This deficiency, as well as potential build-up of fatty acids within the cells, causes the signs and symptoms of the condition.^[1]

Last updated: 7/9/2012

Inheritance Inheritance

Primary carnitine deficiency is inherited in an autosomal recessive manner.^[1] Individuals have two copies of each gene, one of which is inherited from each parent. For an individual to have an autosomal recessive condition, he/she must have a mutation in both copies of the disease-causing gene. The parents of an affected individual, who each likely have one mutated copy, are referred to as carriers. Carriers typically do not have any signs or symptoms of the condition. When two carriers for an autosomal recessive condition have children together, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be a carrier like each of the parents, and a 25% risk to not have the condition and not be a carrier.

Last updated: 7/9/2012

Diagnosis Diagnosis

Primary carnitine deficiency can have a wide range of presentations and the age at diagnosis varies. Affected individuals may be diagnosed due to metabolic decompensation in infancy (between ages 3 months to 2 years); cardiomyopathy in childhood (between 2 and 4 years of age on average); or fatigability in adulthood. Some affected individuals lack symptoms entirely.^[3]

Although the condition is typically associated with the infantile presentation in about half of affected individuals and the childhood myopathic presentation in the other half, affected adults with mild or no symptoms have been reported. Several women have been diagnosed after newborn screening identified low carnitine levels in their infants. About half of those women complained of fatigability, whereas the other half were asymptomatic. In some cases, affected women can have decreased stamina or worsening of cardiac arrhythmia during pregnancy, suggesting that the condition may manifest or exacerbate during pregnancy.^[3]

Last updated: 7/11/2012

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.
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.

Treatment Treatment

Most individuals with primary carnitine deficiency are followed by a metabolic doctor as well as a dietician familiar with this condition. Certain treatments may be advised for some children but not others. Treatment is often needed throughout life. The main treatment for this condition is lifelong use of L-carnitine, which is a natural substance that helps body cells make energy. It also helps the body get rid of harmful wastes. L-carnitine can reverse the heart problems and muscle weakness caused by this condition.^[4]

In addition to L-carnitine, infants and young children with primary carnitine 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. But some babies need to eat even more frequently than this. Many teens and adults with this condition can go without food for up to 12 hours without problems. Some children and teens benefit from a low-fat, high carbohydrate diet. Any diet changes should be made under the guidance of a metabolic specialist and/or dietician familiar with this condition. Ask your doctor whether your child needs to have any changes in his or her diet. Other treatments usually need to be continued throughout life.^[4]

Infants and children with this condition need to eat extra starchy food and drink more fluids during any illness, even if they may not feel hungry, because they could have a metabolic crisis. Children who are sick often do not want to eat. If they won’t or can’t eat, they may need to be treated in the hospital to prevent serious health problems.^[4]

Last updated: 10/17/2011

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.

FDA-Approved Treatments

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

Levocarnitine (Brand name: Carnitor®) - Manufactured by Sigma-Tau Pharmaceuticals, Inc.
FDA-approved indication: Treatment of primary and secondary carnitine deficiency.
National Library of Medicine Drug Information Portal
Medline Plus Health Information

Prognosis Prognosis

Infantile metabolic and childhood myopathic presentations of the condition can be fatal if untreated.^[2] However, long-term prognosis is excellent with oral carnitine supplementation. If the disorder goes unrecognized, death can occur due to cardiac failure, arrhythmias or sudden death. Hypoglycemia or sudden deaths from arrhythmias (even without cardiomyopathy) have been reported in affected individuals who stop their carnitine supplementation against medical advice.^[5]

Individuals who have questions about their specific prognosis should speak with their health care provider.

Last updated: 7/11/2012

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.
You can submit a question to Ask the Mito Doc, a service of the United Mitochondrial Diseases Foundation. Information contained in Ask the Mito Doc^SM is for informational and educational purposes only.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include other fat oxidation defects such as medium chain acyl-CoA dehydrogenase deficiency and very long chain acyl-CoA dehydrogenase deficiency. Visit the Orphanet disease page for more information.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are related to Primary carnitine deficiency. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.
The U.S. National Institutes of Health, through the National Library of Medicine, developed ClinicalTrials.gov to provide patients, family members, and members of the public with current information on clinical research studies. There is a study titled Pediatric Patients With Metabolic or Other Genetic Disorders which may be of interest to you.

Organizations 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

FOD (Fatty Oxidation Disorder) Family Support Group
P.O. Box 54
Okemos, MI 48805-0054
Telephone: +1-517-381-1940 [8am - 8pm EST every day]
Fax: +1-866-290-5206
E-mail: deb@fodsupport.org
Website: https://fodsupport.org/
Metabolic Support UK
5 Hilliards Court
Sandpiper Way
Chester Business Park
Chester, CH4 9QP United Kingdom
Toll-free: 0800 652 3181
Telephone: 0845 241 2173
E-mail: https://www.metabolicsupportuk.org/contact-us
Website: https://www.metabolicsupportuk.org
United Mitochondrial Disease Foundation
8085 Saltsburg Road, Suite 201
Pittsburgh, PA 15239
Toll-free: 1-888-317-8633
Telephone: +1-412-793-8077
Fax: +1-412-793-6477
E-mail: info@umdf.org
Website: https://www.umdf.org

Do you know of an organization? We want to hear from you.

Learn More 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 Primary carnitine deficiency. This website is maintained by the National Library of Medicine.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
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

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
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 Primary carnitine deficiency. Click on the link to view a sample search on this topic.

News & Events News & Events

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Other Conferences

The International Network for Fatty Acid Oxidation Research and Management (INFORM) was formed in order to promote research and discussion into the cause, diagnosis, and management of fatty acid oxidation disorders (FAODs). They offer several learning opportunities throughout the year for patients, families, and researchers. INFORM's Annual Meeting will be held on August 30th and 31st, 2020 in Freiberg, Germany preceding the Society for the Study of Inborn Errors of Metabolism (SSIEM). The Network also continues to provide a collaborative framework for ongoing communication and research regarding FAODs.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

Have a question? Contact a GARD Information Specialist.

References References

Primary carnitine deficiency. Genetics Home Reference. September 2014; http://www.ghr.nlm.nih.gov/condition/primary-carnitine-deficiency.
Ayman W El-Hattab. Systemic Primary Carnitine Deficiency. GeneReviews. November 3, 2016; http://www.ncbi.nlm.nih.gov/books/NBK84551/.
Systemic Primary Carnitine Deficiency. GeneReviews. March 15, 2012; http://www.ncbi.nlm.nih.gov/books/NBK84551/.
Carnitine transporter deficiency. Screening, Technology, and Research in Genetics (STAR-G). 2/20/2016; http://www.newbornscreening.info/Parents/fattyaciddisorders/Carnitine.html.
Fernando Scaglia. Carnitine Deficiency. Medscape Reference. April 13, 2010; http://emedicine.medscape.com/article/942233-overview.