Cited by 140Metabolism and Genetic DisordersDrug Transport and Resistance MechanismsMitochondrial Function and Pathology

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Carnitine transport: Pathophysiology and metabolism of known molecular defects

Tein, I.·2003·Journal of Inherited Metabolic Disease

DOI 10.1023/a:1024481016187

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Abstract

Summary: Early‐onset dilatative and/or hypertrophic cardiomyopathy with episodic hypoglycaemic coma and very low serum and tissue concentrations of carnitine should alert the clinician to the probability of the plasmalemmal high‐affinity carnitine transporter defect. The diagnosis can be established by demonstration of impaired carnitine uptake in cultured skin fibroblasts or lymphoblasts and confirmed by mutation analysis of the human OCTN2 gene in the affected child and obligate heterozygote parents. The institution of high‐dose oral carnitine supplementation reverses the pathology in this otherwise lethal autosomal recessive disease of childhood, and carnitine therapy from birth in prospectively screened siblings may altogether prevent the development of the clinical phenotype. Heterozygotes may be at risk for cardiomyopathy in later adult life, particularly in the presence of additional risk factors such as hypertension and competitive pharmacological agents. OCTN2 belongs to a family of organic cation/carnitine transporters that function primarily in the elimination of cationic drugs and other xenobiotics in kidney, intestine, liver and placenta. The high‐ and low‐affinity human carnitine transporters, OCTN2 and OCTN1, are multifunctional polyspecific organic cation transporters; therefore, defects in these transporters may have widespread implications for the absorption and/or elimination of a number of key pharmacological agents such as cephalosporins, verapamil, quinidine and valproic acid. A third organic/cation carnitine transporter with high specificity for carnitine, Octn3, has been clonedin mice. The juvenile visceral steatosis (jvs) mouse serves as an excellent clinical, biochemical and molecular model for the high‐affinity carnitine transporter OCTN2 defect and is due to a spontaneous point mutation in the murine Octn2 gene on mouse chromosome 11, which is syntenic to the human locus at 5q31 that harbours the human OCTN2 gene.

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Authors: Tein, I.
Affiliations: University of Toronto (CA)
Corresponding author: Tein, I.
ORCID: Tein, I.
Venue: Journal of Inherited Metabolic Disease
Publisher: Wiley
Published: 2003-03
Volume: 26
Issue: 2-3
Pages: 147-169
ISSN: 0141-8955 (ISSN-L)
1573-2665
DOI: 10.1023/a:1024481016187
OpenAlex: W1569055531
Cited by: 140
References: 124
Citations by year: 2026: 3 · 2025: 1 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 4 · 2020: 3 · 2019: 1 · 2018: 1 · 2017: 3 · 2016: 4 · 2015: 4 · 2014: 6 · 2013: 6 · 2012: 11
FWCI: 1.04
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Journal of Inherited Metabolic Disease (publishedVersion)
PubMed (publishedVersion)
Funders: Heart and Stroke Foundation of Canada
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords: carnitine transport, OCTN2, OCTN1, carnitine deficiency, cardiomyopathy, hypoglycemic coma, organic cation transporters, carnitine supplementation, autosomal recessive inheritance, drug transport, cephalosporins, verapamil, quinidine, valproic acid, genotype-phenotype correlation
MeSH terms: Solute Carrier Family 22 Member 5, Animals, Biological Transport, Carnitine, Carrier Proteins, Disease Models, Animal, Humans, Membrane Proteins, Mutation, Valproic Acid, Membrane Transport Proteins, Organic Cation Transport Proteins, Symporters, Mice, Chemical and Drug Induced Liver Injury

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Carnitine transport: Pathophysiology and metabolism of known molecular defects

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