Carnitine Uptake Defect

Other Names

CUD

Carnitine uptake deficiency

Carnitine transporter deficiency

Systemic carnitine deficiency (SCD)

Primary carnitine deficiency

Diagnosis Coding

E71.41, primary carnitine deficiency

Disorder Category

A fatty acid oxidation disorder

Screening

Finding

Decreased C0 and other acylcarnitines (C3, C16, C18)

Tested By

Tandem mass spectrometry (MS/MS); sensitivity=100% (80% with the first screen only [Nicola Longo, personal communication 2006]); specificity=99.97% [Schulze: 2003]

Overview

Carnitine uptake deficieny (CUD) results in urinary carnitine wasting and 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. Mutations in the SLC22A5 gene cause CUD. This gene is responsible for making a protein called OCTN2 that transports carnitine into cells.

Prevalence

Approximately 1 in 40,000 [Koizumi: 1999], with about 1% of the normal US population being heterozygous (carriers) for this condition [Amat: 2008]

Inheritance

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 identified. Gunctional assay (carnitine transport) possible by amniocentesis or CVS.

Other Testing

Genetic testing is possible for at-risk family members if both disease causing mutations of an affected family member have been identified.

Clinical Characteristics

With treatment prior to metabolic crises, outcomes should be normal. Treatment may reverse pre-existing cardiomyopathy and muscle weakness, but not developmental delay. Without treatment, symptoms may begin between birth and three years of age or, in the myopathic form, symptoms usually begin before seven years and may not include metabolic crisis episodes or hypoglycemia. Some children remain asymptomatic for life. Patients are at risk of sudden death from arrhythmia at any age.

Inital signs and symptoms may include:
  • poor appetite
  • vomiting
  • irritability
  • lethargy
  • hypoketotic hypoglycemia
  • sudden death
  • lab findings:
    • anemia
    • metabolic acidosis
    • hypoglycemia

Subsequent finding include:
  • muscle weakness
  • cardiomyopathy
  • cardiac arrhythmia
  • hepatomegaly
  • seizures and
  • brain injury from hypoglycemia

Treatment consists of carnitine supplementation. Mothers with primary carnitine deficiency can be identified by newborn screening of their unaffected infant.[Schimmenti: 2007]

Follow-up Testing after Positive Screen

Plasma and urine carnitine analysis (the latter to measure urinary carnitine reabsorption), carnitine transporter functional analysis in fibroblasts and/or SLC22A5 gene sequencing.

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)).
  • Special diet is not required but frequent feedings and avoidance of fasting is important.
  • 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 if the child is affected. A dietician may work with the family to devise an optimal approach to dietary management. Genetic counseling for the family.

Resources

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.

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.

Newborn Screening ACT Sheets & Confirmatory Algorithms (ACMG)
ACTion (ACT) Sheets and algorithms for responding to positive newborn screening test results, membership required; American College of Medical Genetics.

Resources for Carnitine Uptake Deficiency (Disease InfoSearch)
Compilation of information, articles, research, case studies, and genetics links; from Genetic Alliance.

Carnitine Uptake Deficiency (OMIM)
Extensive review of literature that provides technical information on genetic disorders; Online Mendelian Inheritance in Man site, hosted by Johns Hopkins University.

Genetics in Primary Care Institute (AAP)
The goal of this site is to increase collaboration in the care of children with known or suspected genetic disorders. Includes health supervision guidelines and other useful resources; a collaboration among the Health Resources & Services Administration, the Maternal and Child Health Bureau, and the American Academy of Pediatrics.

Utah Newborn Screening Program (UDOH)
Provides information about the program, related legislation, training for practices, and newborn conditions; Utah Department of Health.

Genetics in Primary Care Institute (AAP)
The goal of this site is to increase collaboration in the care of children with known or suspected genetic disorders. Includes health supervision guidelines and other useful resources; a collaboration among the Health Resources & Services Administration, the Maternal and Child Health Bureau, and the American Academy of Pediatrics.

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 (Genetics Home Reference)
Excellent, detailed review of condition for patients and families; U.S. 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.

Newborn Screening Information for Clinicians (NNSGRC)
Fact sheets, data reports, publications ,and information for clinicians about genetic screening that includes links to state genetic contacts; National Newborn Screening & Global Resource Center.

Services

Genetics-related clinical services throughout the world can be found through Genetics Clinic Directory (GeneTests).

Newborn Screening Programs

See all Newborn Screening Programs services providers (3) in our database.

Pediatric Genetics

See all Pediatric Genetics services providers (5) in our database.

For other services related to this condition, browse our Services categories or search our database.

Authors

Reviewing Authors: Kimberly Hart, MS, LCGC - 6/2012
Nicola Longo, MD, PhD - 3/2011
Content Last Updated: 6/2012

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.

Koizumi A, Nozaki J, Ohura T, Kayo T, Wada Y, Nezu J, Ohashi R, Tamai I, Shoji Y, Takada G, Kibira S, Matsuishi T, Tsuji A.
Genetic epidemiology of the carnitine transporter OCTN2 gene in a Japanese population and phenotypic characterization in Japanese pedigrees with primary systemic carnitine deficiency.
Hum Mol Genet. 1999;8(12):2247-54. 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