Carnitine Uptake Defect

Other Names

Carnitine transporter deficiency


Primary carnitine deficiency

Systemic carnitine deficiency (SCD)

Diagnosis Coding

E71.41, Primary carnitine deficiency

Disorder Category

A fatty acid oxidation disorder



Decreased C0 (free carnitine)

Tested By

Tandem mass spectrometry (MS/MS); sensitivity=100% (80% with the first screen only; specificity=99.97% [Schulze: 2003]


Carnitine uptake defect (CUD) results in urinary carnitine wasting, leading to severe systemic and intracellular carnitine deficiency. The latter results in an intramitochondrial defect in the beta-oxidation of fatty acids that impairs energy production and causes accumulation of free fatty acids. The increased reliance on fat metabolism for energy production during prolonged fasting and/or periods of increased energy demands (fever, stress, lack of sleep) may cause metabolic crises in patients with carnitine deficiency. CUD is caused by having 2 compromising SLC22A5 gene mutations inherited from carrier parents. This gene encodes the protein organic cation transporter 2 (OCTN2), which is responsible for transporting carnitine into cells.


Approximately 1 in 20,000-70,000 in the US with about 1% of the normal US population being heterozygous (carriers) for this condition [Magoulas: 2012] [Amat: 2008]


Autosomal recessive

Prenatal Testing

DNA testing possible by amniocentesis or chorionic villus sampling (CVS) if both disease-causing mutations of an affected family member have been previously identified.

Other Testing

Most cases will be identified soon after birth by Newborn Screening programs. Genetic testing is possible for at-risk family members if both disease-causing mutations of an affected family member have been previously identified.

Clinical Characteristics

With treatment prior to metabolic crises, outcomes are typically excellent with no clinically significant symptoms or medical concerns. Additionally, later treatment may reverse pre-existing cardiomyopathy and muscle weakness, but not developmental delay. Treatment consists of life-long high-dose oral L-carnitine supplementation, which has relatively few side-effects. [Schimmenti: 2007]

Without treatment, symptoms may vary widely in regard to age of onset, organ involvement, and severity of symptoms depending on the subtype. This would include the metabolic type presenting with metabolic crises and liver disease, myopathic form presenting with cardiomyopathy and skeletal muscle disease, late-onset adulthood type presenting with generalized fatigability, and some who may remain asymptomatic well into adulthood. Patients are at risk of sudden death from arrhythmia at any age.

Initial signs and symptoms may include:
  • Poor appetite
  • Vomiting
  • Irritability
  • Lethargy
  • Hypoketotic hypoglycemia
  • Sudden death
  • Lab findings:
    • Anemia
    • Metabolic acidosis
    • Hypoglycemia
Subsequent findings include:
  • Muscle weakness
  • Cardiomyopathy
  • Cardiac arrhythmia
  • Hepatomegaly
  • Seizures
  • Brain injury from hypoglycemia

Follow-up Testing after Positive Screen

Total and free carnitine analysis in plasma and sometimes urine. Plasma carnitines may be measured in the mothers of newborns who screen positive to determine if the screen was a false positive due to severe maternal carnitine deficiency (which may be the result of the mother having CUD or a maternal diet insufficient in natural carnitine).

Primary Care Management

Upon Notification of the + Screen

If the Diagnosis is Confirmed

  • Educate the family regarding signs, symptoms, and the need for urgent care when the infant becomes ill (see Carnitine Uptake Deficiency - Information for Parents (STAR-G)).
  • A special diet is not required, but general avoidance of fasting is recommended.
  • Oral L-carnitine supplements should be continued for life.
  • For those identified after irreversible consequences, assist in management, particularly with developmental and educational interventions.

Specialty Care Collaboration

Initial consultation and ongoing collaboration with a Metabolic Geneticist. A dietician may work with the family to devise an optimal approach to dietary management. Genetic counseling for the family. See Pediatric Genetics (see MT providers [7]).


Information & Support

For Professionals

Carnitine Uptake Deficiency - Information for Professionals (STAR-G)
Structured list of information about the condition and links to more information; Screening, Technology, and Research in Genetics.

Primary Carnitine Deficiency (GARD)
Articles, research, case studies, and genetics links; Genetic and Rare Diseases Information Center.

Carnitine Uptake Deficiency (OMIM)
Information about clinical features, diagnosis, management, and molecular and population genetics; Online Mendelian Inheritance in Man, authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine

For Parents and Patients

Carnitine Uptake Deficiency - Information for Parents (STAR-G)
A fact sheet, written by a genetic counselor and reviewed by metabolic and genetic specialists, for families who have received an initial diagnosis of this newborn disorder; Screening, Technology and Research in Genetics.

Carnitine Uptake Deficiency (MedlinePlus)
Information for families that includes description, frequency, causes, inheritance, other names, and additional resources; from the National Library of Medicine.

Fatty Oxidation Disorders (FOD) Family Support Group
Information for families about fatty acid oxidation disorders, support groups, coping, finances, and links to other sites.


ACT Sheet for Carnitine Uptake Defect (ACMG) (PDF Document 344 KB)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive; American College of Medical Genetics.

Confirmatory Algorithms for Carnitine Uptake Defect (ACMG) (PDF Document)
An algorithm of the basic steps involved in determining the final diagnosis of an infant with a positive newborn screen; American College of Medical Genetics.

Services for Patients & Families in Montana (MT)

Genetics clinic services throughout the US can be found through the Genetics Clinic Services Search Engine (ACMG)

For services not listed above, browse our Services categories or search our database.

* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.

Authors & Reviewers

Initial publication: March 2007; last update/revision: March 2021
Current Authors and Reviewers:
Author: Brian J. Shayota, MD, MPH
Authoring history
2012: revision: Kimberly Hart, MS, LCGCR
2011: first version: Nicola Longo, MD, Ph.D.A
AAuthor; CAContributing Author; SASenior Author; RReviewer

Page Bibliography

Amat di San Filippo C, Taylor MR, Mestroni L, Botto LD, Longo N.
Cardiomyopathy and carnitine deficiency.
Mol Genet Metab.. 2008;94(2):162-166.
Carnitine is essential for the transfer of long-chain fatty acids across the mitochondrial membrane for subsequent beta-oxidation. Study results indicate heterozygosity for primary carnitine deficiency is not more frequent in patients with unselected types of cardiomyopathy and is unlikely to be an important cause of cardiomyopathy in humans.

Magoulas PL, El-Hattab AW, Roy A, Bali DS, Finegold MJ, Craigen WJ.
Diffuse reticuloendothelial system involvement in type IV glycogen storage disease with a novel GBE1 mutation: a case report and review.
Hum Pathol. 2012. PubMed 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;90(4):441-5. PubMed abstract
Primary carnitine deficiency impairs fatty acid oxidation and can result in hypoglycemia, hepatic encephalopathy, cardiomyopathy and sudden death. Given the lifetime risk of morbidity or sudden death, identification of adult patients with primary carnitine deficiency is an added benefit of expanded newborn screening programs.

Schulze A, Lindner M, Kohlmuller D, Olgemoller K, Mayatepek E, Hoffmann GF.
Expanded newborn screening for inborn errors of metabolism by electrospray ionization-tandem mass spectrometry: results, outcome, and implications.
Pediatrics. 2003;111(6 Pt 1):1399-406. PubMed abstract