title: Carnitine transport and fatty acid oxidation.
abstract: Carnitine is essential for the transfer of long-chain fatty acids across the inner mitochondrial membrane for subsequent β-oxidation. It can be synthesized by the body or assumed with the diet from meat and dairy products. Defects in carnitine biosynthesis do not routinely result in low plasma carnitine levels. Carnitine is accumulated by the cells and retained by kidneys using OCTN2, a high affinity organic cation transporter specific for carnitine. Defects in the OCTN2 carnitine transporter results in autosomal recessive primary carnitine deficiency characterized by decreased intracellular carnitine accumulation, increased losses of carnitine in the urine, and low serum carnitine levels. Patients can present early in life with hypoketotic hypoglycemia and hepatic encephalopathy, or later in life with skeletal and cardiac myopathy or sudden death from cardiac arrhythmia, usually triggered by fasting or catabolic state. This disease responds to oral carnitine that, in pharmacological doses, enters cells using the amino acid transporter B(0,+). Primary carnitine deficiency can be suspected from the clinical presentation or identified by low levels of free carnitine (C0) in the newborn screening. Some adult patients have been diagnosed following the birth of an unaffected child with very low carnitine levels in the newborn screening. The diagnosis is confirmed by measuring low carnitine uptake in the patients' fibroblasts or by DNA sequencing of the SLC22A5 gene encoding the OCTN2 carnitine transporter. Some mutations are specific for certain ethnic backgrounds, but the majority are private and identified only in individual families. Although the genotype usually does not correlate with metabolic or cardiac involvement in primary carnitine deficiency, patients presenting as adults tend to have at least one missense mutation retaining residual activity. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou.
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, University of Utah, Salt Lake City, UT, USA; Department of Pathology, University of Utah, and ARUP Laboratories, 500 Chipeta Way, Salt Lake City, UT, USA. Electronic address: Nicola.Longo@hsc.utah.edu.
authors.forename: Nicola
authors.initials: N
authors.lastname: Longo
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, University of Utah, Salt Lake City, UT, USA.
authors.forename: Marta
authors.initials: M
authors.lastname: Frigeni
authors.affiliation: Department of Pathology, University of Utah, and ARUP Laboratories, 500 Chipeta Way, Salt Lake City, UT, USA.
authors.forename: Marzia
authors.initials: M
authors.lastname: Pasquali
mesh_terms: D000328:Adult; D017668:Age of Onset; D001692:Biological Transport; D002331:Carnitine / Q000172:deficiency / Q000378:metabolism* / Q000627:therapeutic use; D022461:Caveolins / Q000378:metabolism; D004734:Energy Metabolism; D005215:Fasting / Q000502:physiology; D050612:Fatty Acid Transport Proteins / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D007668:Kidney / Q000378:metabolism; D009154:Mutation; D015997:Neonatal Screening; D009928:Organ Specificity; D027701:Organic Cation Transport Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D000074058:Solute Carrier Family 22 Member 5
chemical_list: D022461:Caveolins; D050612:Fatty Acid Transport Proteins; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D027701:Organic Cation Transport Proteins; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; D002331:Carnitine
keywords: Arrhythmia; Autism; Carnitine; Newborn screening; OCTN2; SLC22A5
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