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

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Acute encephalopathy	Very frequent (present in 80%-99% of cases)
Clumsiness	Very frequent (present in 80%-99% of cases)
Confusion	Very frequent (present in 80%-99% of cases)
Elevated hepatic transaminases	Very frequent (present in 80%-99% of cases)
Generalized tonic-clonic seizures with focal onset	Very frequent (present in 80%-99% of cases)
Hepatomegaly	Very frequent (present in 80%-99% of cases)
Neck muscle weakness	Very frequent (present in 80%-99% of cases)
Vomiting	Very frequent (present in 80%-99% of cases)
Autosomal recessive inheritance	-
Cardiomegaly	-
Coma	-
Congestive heart failure	-
Decreased carnitine level in liver	-
Decreased plasma carnitine	-
Encephalopathy	-
Endocardial fibroelastosis	-
Excessive daytime somnolence	-
Failure to thrive	-
Hepatic steatosis	-
Hyperammonemia	-
Hypertrophic cardiomyopathy	-
Impaired gluconeogenesis	-
Lethargy	-
Muscular hypotonia	-
Myopathy	-
Recurrent hypoglycemia	-
Reduced muscle carnitine level	-

Last updated: 9/1/2017

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

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare 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.
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.^[3]

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.^[3]

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.^[3]

Last updated: 10/17/2011

Management Guidelines

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.
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.^[4]

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

Last updated: 7/11/2012

Do you have updated information on this condition? Let us know.

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

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. To find this trial, click on the link above.
ClinicalTrials.gov lists trials that are studying or have studied 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.

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

Children Living with Inherited Metabolic Diseases (CLIMB)
Climb Building
176 Nantwich Road
Crewe CW2 6BG
United Kingdom
Toll-free: 0800 652 3181
Telephone: 0845 241 2173
E-mail: contact@climb.org.uk
Website: http://www.climb.org.uk
FOD (Fatty Oxidation Disorder) Family Support Group
P.O. Box 54
Okemos, MI 48805-0054
Telephone: 517-381-1940
Fax: 866-290-5206
E-mail: deb@fodsupport.org
Website: http://www.fodsupport.org
United Mitochondrial Disease Foundation
8085 Saltsburg Road, Suite 201
Pittsburgh, PA 15239
Toll-free: 888-317-8633
Telephone: 412-793-8077
Fax: 412-793-6477
E-mail: info@umdf.org
Website: http://www.umdf.org

Do you know of an organization? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Healthcare Resources

You can submit a question to Ask the Mito Doc^SM , a service of the United Mitochondrial Diseases Foundation. Information contained in Ask the Mito Doc^SM is for informational and educational purposes only.

Genetics 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 GeneTests, 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.

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

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

News

Don’t Miss the NCATS Toolkit for Patient-Focused Therapy Development Event
August 31, 2017
Funding Opportunities Now Available for the Undiagnosed Diseases Network (UDN) Phase II
August 30, 2017
IRDiRC Goals 2017-2027: New Rare Disease Research Goals for the Next Decade
August 10, 2017

Other Conferences

The International Network for Fatty Acid Oxidation Research and Management (INFORM) has been formed in order to promote research and discussion into the cause, diagnosis, and management of inborn errors of fatty acid oxidation. INFORM will sponsor an inaugural symposium to be held on September 6, 2014 in Innsbruck, Austria following SSIEM, with annual meetings thereafter. The Network will provide a collaborative framework for ongoing communication and research between the members.

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. Submit a new question

What is this? Why do I have it? I just had a baby and found out I had it. My sister also just had a baby and has it too. Will we be okay? See answer

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/.
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.