Rare Medical News

Disease Profile

Primary carnitine 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.

Unknown

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

Other names (AKA)

Systemic primary carnitine deficiency; Carnitine uptake defect; Carnitine deficiency, systemic, due to defect in renal reabsorption of carnitine;

Categories

Congenital and Genetic Diseases; Heart Diseases; Metabolic disorders;

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]

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.

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

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]

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]

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

    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]

    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.

      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 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.

              References

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

              Rare Medical News