title: Primary Carnitine Deficiency and Newborn Screening for Disorders of the Carnitine Cycle.
abstract: Carnitine is needed for transfer of long-chain fatty acids across the inner mitochondrial membrane for subsequent β-oxidation. Carnitine can be synthesized by the body and is also obtained in the diet through consumption of meat and dairy products. Defects in carnitine transport such as those caused by defective activity of the OCTN2 transporter encoded by the SLC22A5 gene result in primary carnitine deficiency, and newborn screening programmes can identify patients at risk for this condition before irreversible damage. Initial biochemical diagnosis can be confirmed through molecular testing, although direct study of carnitine transport in fibroblasts is very useful to confirm or exclude primary carnitine deficiency in individuals with genetic variations of unknown clinical significance or who continue to have low levels of carnitine despite negative molecular analyses. Genetic defects in carnitine biosynthesis do not generally result in low plasma levels of carnitine. However, deletion of the trimethyllysine hydroxylase gene, a key gene in carnitine biosynthesis, has been associated with non-dysmorphic autism. Thus, new roles for carnitine are emerging that are unrelated to classic inborn errors of metabolism.
authors.affiliation: Department of Pediatrics and Pathology, ARUP Laboratories, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Nicola
authors.initials: N
authors.lastname: Longo
mesh_terms: D009202:Cardiomyopathies / Q000175:diagnosis* / Q000178:diet therapy / Q000453:epidemiology / Q000378:metabolism; D002331:Carnitine / Q000172:deficiency* / Q000378:metabolism / Q000627:therapeutic use; D003677:Deficiency Diseases / Q000175:diagnosis* / Q000178:diet therapy / Q000378:metabolism; D003718:Denmark / Q000453:epidemiology; D019587:Dietary Supplements; D005820:Genetic Testing; D006801:Humans; D022124:Hyperammonemia / Q000175:diagnosis* / Q000178:diet therapy / Q000453:epidemiology / Q000378:metabolism; D015994:Incidence; D007231:Infant, Newborn; D008661:Metabolism, Inborn Errors / Q000175:diagnosis* / Q000178:diet therapy / Q000235:genetics / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D009135:Muscular Diseases / Q000175:diagnosis* / Q000178:diet therapy / Q000453:epidemiology / Q000378:metabolism; D009154:Mutation; D015997:Neonatal Screening; D011379:Prognosis; D000074058:Solute Carrier Family 22 Member 5 / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism
chemical_list: C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; D006899:Mixed Function Oxygenases; C025931:trimethyl-lysine hydroxylase; D002331:Carnitine