{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T13:13:46Z","timestamp":1791983626769,"version":"4.4.0"},"reference-count":10,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,1,12]],"date-time":"2006-01-12T00:00:00Z","timestamp":1137024000000},"content-version":"vor","delay-in-days":437,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2004,11]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      A\n                      <jats:sc>bstract<\/jats:sc>\n                      :\n                    <\/jats:bold>\n                    Mitochondrial oxidation of long\u2010chain fatty acids provides an important source of energy for the heart as well as for skeletal muscle during prolonged aerobic work and for hepatic ketogenesis during long\u2010term fasting. The carnitine shuttle is responsible for transferring long\u2010chain fatty acids across the barrier of the inner mitochondrial membrane to gain access to the enzymes of \u03b2\u2010oxidation. The shuttle consists of three enzymes (carnitine palmitoyltransferase 1, carnitine acylcarnitine translocase, carnitine palmitoyl\u2010transferase 2) and a small, soluble molecule, carnitine, to transport fatty acids as their long\u2010chain fatty acylcarnitine esters. Carnitine is provided in the diet (animal protein) and also synthesized at low rates from trimethyl\u2010lysine residues generated during protein catabolism. Carnitine turnover rates (300\u2010500 \u03bcmol\/day) are &lt;1% of body stores; 98% of carnitine stores are intracellular (total carnitine levels are 40\u201050 \u03bcM in plasma vs. 2\u20103 mM in tissue). Carnitine is removed by urinary excretion after reabsorption of 98% of the filtered load; the renal carnitine threshold determines plasma concentrations and total body carnitine stores. Because of its key role in fatty acid oxidation, there has long been interest in the possibility that carnitine might be of benefit in genetic or acquired disorders of energy production to improve fatty acid oxidation, to remove accumulated toxic fatty acyl\u2010CoA metabolites, or to restore the balance between free and acyl\u2010CoA. Two disorders have been described in children where the supply of carnitine becomes limiting for fatty acid oxidation: (1) A recessive defect of the muscle\/kidney sodium\u2010dependent, plasma membrane carnitine symporter, which presents in infancy with cardiomyopathy or hypoketotic hypoglycemia; treatment with oral carnitine is required for survival. (2) Chronic administration of pivalate\u2010conjugated antibiotics in which excretion of pivaloyl\u2010carnitine can lead to carnitine depletion; tissue levels may become low enough to limit fatty acid oxidation, although no cases of illness due to carnitine deficiency have been described. There is speculation that carnitine supplements might be beneficial in other settings (such as genetic acyl\u2010CoA oxidation defects\u2014\u201csecondary carnitine deficiency\u201d, chronic ischemia, hyperalimentation, nutritional carnitine deficiency), but efficacy has not been documented. The formation of abnormal acylcarnitines has been helpful in expanded newborn screening programs using tandem mass\u2010spectrometry of blood spot acylcarnitine profiles to detect genetic fatty acid oxidation defects in neonates. Carnitine\u2010deficient diets (vegetarian) do not have much effect on carnitine pools in adults. A modest 50% reduction in carnitine levels is associated with hyperalimentation in newborn infants, but is of doubtful significance. The above considerations indicate that carnitine does not become rate\u2010limiting unless extremely low; testing the benefits of nutritional supplements may require invasive endurance studies of fasting ketogenesis or muscle and cardiovascular work.\n                  <\/jats:p>","DOI":"10.1196\/annals.1320.004","type":"journal-article","created":{"date-parts":[[2004,12,8]],"date-time":"2004-12-08T18:33:28Z","timestamp":1102530808000},"page":"42-51","source":"Crossref","is-referenced-by-count":195,"title":["Carnitine Deficiency Disorders in Children"],"prefix":"10.1111","volume":"1033","author":[{"given":"CHARLES A.","family":"STANLEY","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,7,8]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0065-3101(24)00116-6","article-title":"Carnitine disorders","volume":"42","author":"Stanley C.A.","year":"1995","journal-title":"Adv. Pediatr"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/1098-1004(200011)16:5<401::AID-HUMU4>3.0.CO;2-J"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.5.2356"},{"key":"e_1_2_7_5_2","doi-asserted-by":"crossref","unstructured":"Treem W.R. C.A. Stanley D.N. Finegoldet al.1988. Primary carnitine deficiency due to a failure of carnitine transport in kidney muscle and fibroblasts. N. Engl. J. Med.319:1331\u20131336.","DOI":"10.1056\/NEJM198811173192006"},{"key":"e_1_2_7_6_2","doi-asserted-by":"crossref","unstructured":"Stanley C.A. S. DeLeeuw P.M. Coateset al.1991. Chronic cardiomyopathy and weakness or acute coma in children with a defect in carnitine uptake. Ann. Neurol.30:709\u2013716.","DOI":"10.1002\/ana.410300512"},{"key":"e_1_2_7_7_2","doi-asserted-by":"crossref","unstructured":"Cederbaum S.D. S. Koo\u2010McCoy I. Teinet al.2002. Carnitine membrane transporter deficiency: a long\u2010term follow up and OCTN2 mutation in the first documented case of primary carnitine deficiency. Mol. Genet. Metab.77:195\u2013201.","DOI":"10.1016\/S1096-7192(02)00169-5"},{"key":"e_1_2_7_8_2","doi-asserted-by":"crossref","unstructured":"Holme E. C.E. Jacobson I. Nordinet al.1989. Carnitine deficiency induced by pivampicillin and pivmecillinam therapy. Lancet2:469\u2013472.","DOI":"10.1016\/S0140-6736(89)92086-2"},{"key":"e_1_2_7_9_2","doi-asserted-by":"crossref","unstructured":"Roe C.R. D.S. Millington D.A. Maltbyet al.1984. l\u2010Carnitine enhances excretion of propionyl coenzyme A as propionylcarnitine in propionic acidemia. J. Clin. Invest.73:1785\u20131788.","DOI":"10.1172\/JCI111387"},{"key":"e_1_2_7_10_2","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1542\/peds.93.6.891","article-title":"The role of carnitine supplementation in valproic acid therapy","volume":"93","author":"Kelley R.I.","year":"1994","journal-title":"Pediatrics"},{"key":"e_1_2_7_11_2","doi-asserted-by":"crossref","unstructured":"Stanley C.A. G.T. Berry M.J. Bennettet al.1993. Renal handling of carnitine in secondary carnitine deficiency disorders. Pediatr. Res.34:89\u201397.","DOI":"10.1203\/00006450-199307000-00021"}],"container-title":["Annals of the New York Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1196%2Fannals.1320.004","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/nyaspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1196\/annals.1320.004","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T07:44:35Z","timestamp":1705391075000},"score":1,"resource":{"primary":{"URL":"https:\/\/nyaspubs.onlinelibrary.wiley.com\/doi\/10.1196\/annals.1320.004"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,11]]},"references-count":10,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2004,11]]}},"alternative-id":["10.1196\/annals.1320.004"],"URL":"https:\/\/doi.org\/10.1196\/annals.1320.004","archive":["Portico"],"relation":{},"ISSN":["0077-8923","1749-6632"],"issn-type":[{"value":"0077-8923","type":"print"},{"value":"1749-6632","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,11]]}}}