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Carnitine transport: pathophysiology and metabolism of known molecular defects.
J Inherit Metab Dis. 2003; 26(2-3):147-69.JI

Abstract

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 cloned in 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.

Authors+Show Affiliations

Division of Neurology, Department of Pediatrics, The Hospital for Sick Children, Toronto, Canada. ingrid.tein@sickkids.ca

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

12889657

Citation

Tein, I. "Carnitine Transport: Pathophysiology and Metabolism of Known Molecular Defects." Journal of Inherited Metabolic Disease, vol. 26, no. 2-3, 2003, pp. 147-69.
Tein I. Carnitine transport: pathophysiology and metabolism of known molecular defects. J Inherit Metab Dis. 2003;26(2-3):147-69.
Tein, I. (2003). Carnitine transport: pathophysiology and metabolism of known molecular defects. Journal of Inherited Metabolic Disease, 26(2-3), 147-69.
Tein I. Carnitine Transport: Pathophysiology and Metabolism of Known Molecular Defects. J Inherit Metab Dis. 2003;26(2-3):147-69. PubMed PMID: 12889657.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Carnitine transport: pathophysiology and metabolism of known molecular defects. A1 - Tein,I, PY - 2003/8/2/pubmed PY - 2004/3/6/medline PY - 2003/8/2/entrez SP - 147 EP - 69 JF - Journal of inherited metabolic disease JO - J Inherit Metab Dis VL - 26 IS - 2-3 N2 - 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 cloned in 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. SN - 0141-8955 UR - https://www.unboundmedicine.com/medline/citation/12889657/Carnitine_transport:_pathophysiology_and_metabolism_of_known_molecular_defects_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0141-8955&date=2003&volume=26&issue=2-3&spage=147 DB - PRIME DP - Unbound Medicine ER -