{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T12:13:50Z","timestamp":1789906430636,"version":"4.0.1"},"reference-count":115,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2019,9,6]],"date-time":"2019-09-06T00:00:00Z","timestamp":1567728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Carnitine plays essential roles in intermediary metabolism. In non-vegetarians, most of carnitine sources (~75%) are obtained from diet whereas endogenous synthesis accounts for around 25%. Renal carnitine reabsorption along with dietary intake and endogenous production maintain carnitine homeostasis. The precursors for carnitine biosynthesis are lysine and methionine. The biosynthetic pathway involves four enzymes: 6-N-trimethyllysine dioxygenase (TMLD), 3-hydroxy-6-N-trimethyllysine aldolase (HTMLA), 4-N-trimethylaminobutyraldehyde dehydrogenase (TMABADH), and \u03b3-butyrobetaine dioxygenase (BBD). OCTN2 (organic cation\/carnitine transporter novel type 2) transports carnitine into the cells. One of the major functions of carnitine is shuttling long-chain fatty acids across the mitochondrial membrane from the cytosol into the mitochondrial matrix for \u03b2-oxidation. This transport is achieved by mitochondrial carnitine\u2013acylcarnitine cycle, which consists of three enzymes: carnitine palmitoyltransferase I (CPT I), carnitine-acylcarnitine translocase (CACT), and carnitine palmitoyltransferase II (CPT II). Carnitine inborn errors of metabolism could result from defects in carnitine biosynthesis, carnitine transport, or mitochondrial carnitine\u2013acylcarnitine cycle. The presentation of these disorders is variable but common findings include hypoketotic hypoglycemia, cardio(myopathy), and liver disease. In this review, the metabolism and homeostasis of carnitine are discussed. Then we present details of different inborn errors of carnitine metabolism, including clinical presentation, diagnosis, and treatment options. At the end, we discuss some of the causes of secondary carnitine deficiency.<\/jats:p>","DOI":"10.3390\/molecules24183251","type":"journal-article","created":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T03:14:41Z","timestamp":1567998881000},"page":"3251","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":114,"title":["Carnitine Inborn Errors of Metabolism"],"prefix":"10.3390","volume":"24","author":[{"given":"Mohammed","family":"Almannai","sequence":"first","affiliation":[{"name":"Section of Medical Genetics, Children\u2019s Hospital, King Fahad Medical City, Riyadh 11525, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Majid","family":"Alfadhel","sequence":"additional","affiliation":[{"name":"Division of Genetics, Department of Pediatrics, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs (MNGHA), Riyadh 11426, Saudi Arabia"},{"name":"King Abdullah International Medical Research Center (KAIMRC), Riyadh 11426, Saudi Arabia"},{"name":"College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11426, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayman W.","family":"El-Hattab","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.cmet.2015.05.014","article-title":"Acetyl Coenzyme A: A Central Metabolite and Second Messenger","volume":"21","author":"Pietrocola","year":"2015","journal-title":"Cell Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/s41387-018-0017-1","article-title":"Role of carnitine and its derivatives in the development and management of type 2 diabetes","volume":"8","author":"Bene","year":"2018","journal-title":"Nutr. Diabetes"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1042\/bj3610417","article-title":"Carnitine biosynthesis in mammals","volume":"361","author":"Vaz","year":"2002","journal-title":"Biochem. J."},{"key":"ref_4","first-page":"S3","article-title":"Biosynthesis and metabolism of carnitine","volume":"10","author":"Carter","year":"1995","journal-title":"J. Child Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.gene.2013.10.017","article-title":"L-carnitine supplementation as a potential antioxidant therapy for inherited neurometabolic disorders","volume":"533","author":"Ribas","year":"2014","journal-title":"Gene"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/1475-2891-13-79","article-title":"Effects of L-carnitine supplementation on oxidative stress and antioxidant enzymes activities in patients with coronary artery disease: A randomized, placebo-controlled trial","volume":"13","author":"Lee","year":"2014","journal-title":"Nutr. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.jpeds.2006.09.042","article-title":"Histopathologic abnormalities of the lymphoreticular tissues in organic cation transporter 2 deficiency: Evidence for impaired B cell maturation","volume":"150","author":"Havasi","year":"2007","journal-title":"J. Pediatr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"333","DOI":"10.17219\/acem\/61609","article-title":"L-carnitine treatment of insulin resistance: A systematic review and meta-analysis","volume":"26","author":"Xu","year":"2017","journal-title":"Adv. Clin. Exp. Med. Off. Organ Wroclaw Med. Univ."},{"key":"ref_9","first-page":"3379","article-title":"Carnitine function and requirements during the life cycle","volume":"6","author":"Rebouche","year":"1992","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1196\/annals.1320.004","article-title":"Carnitine deficiency disorders in children","volume":"1033","author":"Stanley","year":"2004","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1006\/abbi.1996.0203","article-title":"Characterization of the human plasmalemmal carnitine transporter in cultured skin fibroblasts","volume":"329","author":"Tein","year":"1996","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2422","DOI":"10.1016\/j.bbamcr.2016.01.023","article-title":"Carnitine transport and fatty acid oxidation","volume":"1863","author":"Longo","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2150","DOI":"10.1093\/clinchem\/47.12.2150","article-title":"Age and sex dependency of carnitine concentration in human serum and skeletal muscle","volume":"47","author":"Opalka","year":"2001","journal-title":"Clin. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1196\/annals.1320.003","article-title":"Kinetics, pharmacokinetics, and regulation of L-carnitine and acetyl-L-carnitine metabolism","volume":"1033","author":"Rebouche","year":"2004","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1002\/iub.323","article-title":"Enzymology of the carnitine biosynthesis pathway","volume":"62","author":"Strijbis","year":"2010","journal-title":"IUBMB Life"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.ymgme.2015.09.004","article-title":"Disorders of carnitine biosynthesis and transport","volume":"116","author":"Scaglia","year":"2015","journal-title":"Mol. Genet. Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4360","DOI":"10.1093\/hmg\/ddr363","article-title":"Use of array CGH to detect exonic copy number variants throughout the genome in autism families detects a novel deletion in TMLHE","volume":"20","author":"Shaw","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7974","DOI":"10.1073\/pnas.1120210109","article-title":"A common X-linked inborn error of carnitine biosynthesis may be a risk factor for nondysmorphic autism","volume":"109","author":"Violante","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e179","DOI":"10.1038\/tp.2012.102","article-title":"Analysis of the chromosome X exome in patients with autism spectrum disorders identified novel candidate genes, including TMLHE","volume":"2","author":"Nava","year":"2012","journal-title":"Transl. Psychiatry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2162","DOI":"10.1002\/ajmg.a.37144","article-title":"Improvement of regressive autism symptoms in a child with TMLHE deficiency following carnitine supplementation","volume":"167A","author":"Ziats","year":"2015","journal-title":"Am. J. Med. Genet. A."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Beaudet, A.L. (2017). Brain carnitine deficiency causes nonsyndromic autism with an extreme male bias: A hypothesis. BioEssays News Rev. Mol. Cell. Dev. Biol., 39.","DOI":"10.1002\/bies.201700012"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7","DOI":"10.4331\/wjbc.v10.i1.7","article-title":"Autism and carnitine: A possible link","volume":"10","author":"Demarquoy","year":"2019","journal-title":"World J. Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Rashidi-Nezhad, A., Talebi, S., Saebnouri, H., Akrami, S.M., and Reymond, A. (2014). The effect of homozygous deletion of the BBOX1 and Fibin genes on carnitine level and acyl carnitine profile. BMC Med. Genet., 15.","DOI":"10.1186\/1471-2350-15-75"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.psychres.2017.10.018","article-title":"BBOX1 is down-regulated in maternal immune-activated mice and implicated in genetic susceptibility to human schizophrenia","volume":"259","author":"Lee","year":"2018","journal-title":"Psychiatry Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/5030","article-title":"Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter","volume":"21","author":"Nezu","year":"1999","journal-title":"Nat. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.ymgme.2014.07.009","article-title":"Inborn errors of metabolism identified via newborn screening: Ten-year incidence data and costs of nutritional interventions for research agenda planning","volume":"113","author":"Therrell","year":"2014","journal-title":"Mol. Genet. Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1093\/hmg\/8.12.2247","article-title":"Genetic epidemiology of the carnitine transporter OCTN2 gene in a Japanese population and phenotypic characterization in Japanese pedigrees with primary systemic carnitine deficiency","volume":"8","author":"Koizumi","year":"1999","journal-title":"Hum. Mol. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1124\/mol.59.2.358","article-title":"Molecular and physiological evidence for multifunctionality of carnitine\/organic cation transporter OCTN2","volume":"59","author":"Ohashi","year":"2001","journal-title":"Mol. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1023\/A:1025968502527","article-title":"Silent and symptomatic primary carnitine deficiency within the same family due to identical mutations in the organic cation\/carnitine transporter OCTN2","volume":"26","author":"Spiekerkoetter","year":"2003","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_30","unstructured":"Adam, M.P., Ardinger, H.H., Pagon, R.A., Wallace, S.E., Bean, L.J., Stephens, K., and Amemiya, A. (1993). Systemic Primary Carnitine Deficiency. GeneReviews\u00ae, University of Washington, Seattle."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/1750-1172-7-68","article-title":"Systemic primary carnitine deficiency: An overview of clinical manifestations, diagnosis, and management","volume":"7","author":"Magoulas","year":"2012","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1007\/s10545-006-0376-y","article-title":"Carnitine transporter defect: Diagnosis in asymptomatic adult women following analysis of acylcarnitines in their newborn infants","volume":"29","author":"Vijay","year":"2006","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.ymgme.2006.10.003","article-title":"Expanded newborn screening identifies maternal primary carnitine deficiency","volume":"90","author":"Schimmenti","year":"2007","journal-title":"Mol. Genet. Metab."},{"key":"ref_34","first-page":"19","article-title":"Maternal systemic primary carnitine deficiency uncovered by newborn screening: Clinical, biochemical, and molecular aspects","volume":"12","author":"Li","year":"2010","journal-title":"Genet. Med. Off. J. Am. Coll. Med. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1002\/humu.21607","article-title":"Genotype-phenotype correlation in primary carnitine deficiency","volume":"33","author":"Rose","year":"2012","journal-title":"Hum. Mutat."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s10545-012-9488-8","article-title":"Primary carnitine deficiency and pivalic acid exposure causing encephalopathy and fatal cardiac events","volume":"36","author":"Rasmussen","year":"2013","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_37","first-page":"34","article-title":"Defective urinary carnitine transport in heterozygotes for primary carnitine deficiency","volume":"1","author":"Scaglia","year":"1998","journal-title":"Genet. Med. Off. J. Am. Coll. Med. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"B270","DOI":"10.1093\/gerona\/57.7.B270","article-title":"Age-associated cardiomyopathy in heterozygous carrier mice of a pathological mutation of carnitine transporter gene, OCTN2","volume":"57","author":"Xiaofei","year":"2002","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_39","first-page":"497","article-title":"Pressure overload-induced cardiomyopathy in heterozygous carrier mice of carnitine transporter gene mutation","volume":"50","author":"Takahashi","year":"2007","journal-title":"Hypertens. Dallas Tex. 1979"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s10557-016-6647-4","article-title":"A Moderate Carnitine Deficiency Exacerbates Isoproterenol-Induced Myocardial Injury in Rats","volume":"30","author":"Giudice","year":"2016","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.hrthm.2015.07.027","article-title":"Carnitine deficiency induces a short QT syndrome","volume":"13","author":"Roussel","year":"2016","journal-title":"Heart Rhythm"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1007\/s12630-016-0797-5","article-title":"L-carnitine reduces susceptibility to bupivacaine-induced cardiotoxicity: An experimental study in rats","volume":"64","author":"Wong","year":"2017","journal-title":"Can. J. Anaesth. J. Can. Anesth."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.ymgme.2008.02.002","article-title":"Cardiomyopathy and carnitine deficiency","volume":"94","author":"Taylor","year":"2008","journal-title":"Mol. Genet. Metab."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1067\/mpd.2001.111813","article-title":"Carnitine transporter defect diagnosed by newborn screening with electrospray tandem mass spectrometry","volume":"138","author":"Wilcken","year":"2001","journal-title":"J. Pediatr."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/0009-8981(95)06148-7","article-title":"Plasma carnitine concentrations in pregnancy, cord blood, and neonates and children","volume":"243","author":"Winter","year":"1995","journal-title":"Clin. Chim. Acta Int. J. Clin. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.ymgme.2017.06.015","article-title":"Biochemical characteristics of newborns with carnitine transporter defect identified by newborn screening in California","volume":"122","author":"Gallant","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3492","DOI":"10.3748\/wjg.v21.i12.3492","article-title":"Long-chain acyl-CoA synthetase in fatty acid metabolism involved in liver and other diseases: An update","volume":"21","author":"Yan","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2736","DOI":"10.1194\/jlr.M700378-JLR200","article-title":"Evidence for 26 distinct acyl-coenzyme A synthetase genes in the human genome","volume":"48","author":"Watkins","year":"2007","journal-title":"J. Lipid Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1432-1033.1997.00001.x","article-title":"The mitochondrial carnitine palmitoyltransferase system. From concept to molecular analysis","volume":"244","author":"McGarry","year":"1997","journal-title":"Eur. J. Biochem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1007\/s10545-010-9061-2","article-title":"A general introduction to the biochemistry of mitochondrial fatty acid \u03b2-oxidation","volume":"33","author":"Houten","year":"2010","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1002\/acn3.717","article-title":"A novel CPT1C variant causes pure hereditary spastic paraplegia with benign clinical course","volume":"6","author":"Hong","year":"2019","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1001\/jamaneurol.2014.4769","article-title":"Mutation in CPT1C Associated with Pure Autosomal Dominant Spastic Paraplegia","volume":"72","author":"Rinaldi","year":"2015","journal-title":"JAMA Neurol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1007\/s10545-010-9076-8","article-title":"Newborn screening for disorders of fatty-acid oxidation: Experience and recommendations from an expert meeting","volume":"33","author":"Lindner","year":"2010","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.ymgme.2010.07.013","article-title":"Carnitine palmitoyltransferase 1A (CPT1A) P479L prevalence in live newborns in Yukon, Northwest Territories, and Nunavut","volume":"101","author":"Collins","year":"2010","journal-title":"Mol. Genet. Metab."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1006\/mgme.2001.3149","article-title":"Hepatic carnitine palmitoyl transferase 1 (CPT1 A) deficiency in North American Hutterites (Canadian and American): Evidence for a founder effect and results of a pilot study on a DNA-based newborn screening program","volume":"73","author":"Prasad","year":"2001","journal-title":"Mol. Genet. Metab."},{"key":"ref_56","unstructured":"Adam, M.P., Ardinger, H.H., Pagon, R.A., Wallace, S.E., Bean, L.J., Stephens, K., and Amemiya, A. (1993). Carnitine Palmitoyltransferase 1A Deficiency. GeneReviews\u00ae, University of Washington, Seattle."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/ajmg.c.30087","article-title":"Disorders of carnitine transport and the carnitine cycle","volume":"142C","author":"Longo","year":"2006","journal-title":"Am. J. Med. Genet. C Semin. Med. Genet."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1023\/A:1005694320063","article-title":"Features of carnitine palmitoyltransferase type I deficiency","volume":"24","author":"Olpin","year":"2001","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.mam.2004.06.004","article-title":"Carnitine palmitoyltransferases 1 and 2: Biochemical, molecular and medical aspects","volume":"25","author":"Bonnefont","year":"2004","journal-title":"Mol. Aspects Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1203\/00006450-200001000-00010","article-title":"Hepatic carnitine palmitoyltransferase I deficiency presenting as maternal illness in pregnancy","volume":"47","author":"Innes","year":"2000","journal-title":"Pediatr. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.ymgme.2013.04.008","article-title":"Differences between acylcarnitine profiles in plasma and bloodspots","volume":"110","author":"Diekman","year":"2013","journal-title":"Mol. Genet. Metab."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.ymgme.2010.06.012","article-title":"ESI-MS\/MS measurement of free carnitine and its precursor \u03b3-butyrobetaine in plasma and dried blood spots from patients with organic acidurias and fatty acid oxidation disorders","volume":"101","author":"Primassin","year":"2010","journal-title":"Mol. Genet. Metab."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.ymgme.2005.07.022","article-title":"Novel metabolic and molecular findings in hepatic carnitine palmitoyltransferase I deficiency","volume":"86","author":"Korman","year":"2005","journal-title":"Mol. Genet. Metab."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.mam.2011.10.008","article-title":"The mitochondrial carnitine\/acylcarnitine carrier: Function, structure and physiopathology","volume":"32","author":"Indiveri","year":"2011","journal-title":"Mol. Aspects Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.mam.2004.06.007","article-title":"Carnitine-acylcarnitine translocase deficiency, clinical, biochemical and genetic aspects","volume":"25","author":"Bakker","year":"2004","journal-title":"Mol. Aspects Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s004310000644","article-title":"Carnitine-acylcarnitine translocase deficiency: Phenotype, residual enzyme activity and outcome","volume":"160","author":"Lopriore","year":"2001","journal-title":"Eur. J. Pediatr."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/S0022-3476(98)70030-7","article-title":"A patient with carnitine-acylcarnitine translocase deficiency with a mild phenotype","volume":"132","author":"Morris","year":"1998","journal-title":"J. Pediatr."},{"key":"ref_68","unstructured":"Adam, M.P., Ardinger, H.H., Pagon, R.A., Wallace, S.E., Bean, L.J., Stephens, K., and Amemiya, A. (1993). Carnitine Palmitoyltransferase II Deficiency. GeneReviews\u00ae, University of Washington, Seattle."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1002\/mus.24606","article-title":"Diagnostic evaluation of rhabdomyolysis","volume":"51","author":"Nance","year":"2015","journal-title":"Muscle Nerve"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1212\/01.WNL.0000055901.58642.48","article-title":"Carnitine palmitoyltransferase II deficiency: Molecular and biochemical analysis of 32 patients","volume":"60","author":"Wieser","year":"2003","journal-title":"Neurology"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1001\/archneur.62.1.37","article-title":"Muscle carnitine palmitoyltransferase II deficiency: Clinical and molecular genetic features and diagnostic aspects","volume":"62","author":"Deschauer","year":"2005","journal-title":"Arch. Neurol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1179\/016164110X12767786356390","article-title":"Genotype-phenotype correlations in a large series of patients with muscle type CPT II deficiency","volume":"33","author":"Anichini","year":"2011","journal-title":"Neurol. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1002\/mus.10217","article-title":"Phenotypic variability among first-degree relatives with carnitine palmitoyltransferase II deficiency","volume":"26","author":"Vladutiu","year":"2002","journal-title":"Muscle Nerve"},{"key":"ref_74","first-page":"SD01","article-title":"Neonatal Carnitine Palmitoyltransferase II Deficiency: A Lethal Entity","volume":"9","author":"Malik","year":"2015","journal-title":"J. Clin. Diagn. Res. JCDR"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1067\/mpd.2002.128545","article-title":"Lethal neonatal and severe late infantile forms of carnitine palmitoyltransferase II deficiency associated with compound heterozygosity for different protein truncation mutations","volume":"141","author":"Vladutiu","year":"2002","journal-title":"J. Pediatr."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1111\/cge.12593","article-title":"Diagnostic pitfall in antenatal manifestations of CPT II deficiency","volume":"89","author":"Boemer","year":"2016","journal-title":"Clin. Genet."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.ymgme.2008.05.002","article-title":"CPT2 gene mutations resulting in lethal neonatal or severe infantile carnitine palmitoyltransferase II deficiency","volume":"94","author":"Isackson","year":"2008","journal-title":"Mol. Genet. Metab."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.ymgme.2017.07.011","article-title":"Newborn screening for carnitine palmitoyltransferase II deficiency using (C16+C18:1)\/C2: Evaluation of additional indices for adequate sensitivity and lower false-positivity","volume":"122","author":"Tajima","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3109","DOI":"10.1021\/jm100809g","article-title":"Carnitine palmitoyltransferase (CPT) modulators: A medicinal chemistry perspective on 35 years of research","volume":"54","author":"Ceccarelli","year":"2011","journal-title":"J. Med. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"773","DOI":"10.2337\/diacare.15.6.773","article-title":"Rationale and application of fatty acid oxidation inhibitors in treatment of diabetes mellitus","volume":"15","author":"Foley","year":"1992","journal-title":"Diabetes Care"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"644","DOI":"10.2337\/db10-0346","article-title":"Selective reversible inhibition of liver carnitine palmitoyl-transferase 1 by teglicar reduces gluconeogenesis and improves glucose homeostasis","volume":"60","author":"Conti","year":"2011","journal-title":"Diabetes"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1586\/14779072.5.6.1123","article-title":"Metabolic therapy for the treatment of ischemic heart disease: Reality and expectations","volume":"5","author":"Wang","year":"2007","journal-title":"Expert Rev. Cardiovasc. Ther."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.cardiores.2005.02.004","article-title":"Carnitine palmitoyl transferase-I inhibition prevents ventricular remodeling and delays decompensation in pacing-induced heart failure","volume":"66","author":"Lionetti","year":"2005","journal-title":"Cardiovasc. Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1007\/s00059-002-2428-x","article-title":"The use of partial fatty acid oxidation inhibitors for metabolic therapy of angina pectoris and heart failure","volume":"27","author":"Rupp","year":"2002","journal-title":"Herz"},{"key":"ref_85","first-page":"205","article-title":"A double-blind randomized multicentre clinical trial to evaluate the efficacy and safety of two doses of etomoxir in comparison with placebo in patients with moderate congestive heart failure: The ERGO (etomoxir for the recovery of glucose oxidation) study","volume":"113","author":"Holubarsch","year":"2007","journal-title":"Clin. Sci. Lond. Engl. 1979"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e2226","DOI":"10.1038\/cddis.2016.132","article-title":"Fatty acid oxidation and carnitine palmitoyltransferase I: Emerging therapeutic targets in cancer","volume":"7","author":"Qu","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/S0146-0005(99)80047-0","article-title":"Primary and secondary alterations of neonatal carnitine metabolism","volume":"23","author":"Scaglia","year":"1999","journal-title":"Semin. Perinatol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1743-7075-7-30","article-title":"Role of carnitine in disease","volume":"7","author":"Flanagan","year":"2010","journal-title":"Nutr. Metab."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1093\/ajcn\/50.2.301","article-title":"Carnitine status of lactoovovegetarians and strict vegetarian adults and children","volume":"50","author":"Lombard","year":"1989","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1007\/s11606-007-0473-0","article-title":"Hyperammonemic Encephalopathy Caused by Carnitine Deficiency","volume":"23","author":"Limketkai","year":"2008","journal-title":"J. Gen. Intern. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"381","DOI":"10.3233\/NPM-16146","article-title":"Carnitine deficiency in preterm infants: A national survey of knowledge and practices","volume":"10","author":"Clark","year":"2017","journal-title":"J. Neonatal-Perinat. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1159\/000243302","article-title":"Carnitine and total parenteral nutrition of the neonate","volume":"58","author":"Penn","year":"1990","journal-title":"Biol. Neonate"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1093\/pch\/9.8.573","article-title":"In preterm infants, does the supplementation of carnitine to parenteral nutrition improve the following clinical outcomes: Growth, lipid metabolism and apneic spells?","volume":"9","year":"2004","journal-title":"Paediatr. Child Health"},{"key":"ref_94","first-page":"168","article-title":"A systematic review about prophylactic L-carnitine administration in parenteral nutrition of extremely preterm infants","volume":"42","year":"2018","journal-title":"Farm. Hosp. Organo Expresion Cient. Soc. Espanola Farm. Hosp."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1080\/15563650902752376","article-title":"Carnitine in the treatment of valproic acid-induced toxicity","volume":"47","author":"Lheureux","year":"2009","journal-title":"Clin. Toxicol. Phila. Pa"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.jpeds.2016.02.080","article-title":"Clinical Features of Carnitine Deficiency Secondary to Pivalate-Conjugated Antibiotic Therapy","volume":"173","author":"Kobayashi","year":"2016","journal-title":"J. Pediatr."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.cbi.2008.10.052","article-title":"Inactivation by omeprazole of the carnitine transporter (OCTN2) reconstituted in liposomes","volume":"179","author":"Pochini","year":"2009","journal-title":"Chem. Biol. Interact."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1016\/j.bbamem.2006.07.002","article-title":"Mechanism of the inhibitory effect of zwitterionic drugs (levofloxacin and grepafloxacin) on carnitine transporter (OCTN2) in Caco-2 cells","volume":"1758","author":"Hirano","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1158\/1535-7163.MCT-11-0980","article-title":"Inhibition of OCTN2-mediated transport of carnitine by etoposide","volume":"11","author":"Hu","year":"2012","journal-title":"Mol. Cancer Ther."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"S13","DOI":"10.1016\/S0272-6386(03)00113-6","article-title":"Dialysis-related carnitine disorder and levocarnitine pharmacology","volume":"41","author":"Evans","year":"2003","journal-title":"Am. J. Kidney Dis. Off. J. Natl. Kidney Found."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1111\/j.1523-1755.2004.00916.x","article-title":"Impact of hemodialysis on endogenous plasma and muscle carnitine levels in patients with end-stage renal disease","volume":"66","author":"Evans","year":"2004","journal-title":"Kidney Int."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1111\/j.1525-139X.2006.00180.x","article-title":"Dialysis-related carnitine disorder","volume":"19","author":"Hedayati","year":"2006","journal-title":"Semin. Dial."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/sdi.12041","article-title":"L-carnitine supplementation in dialysis: Treatment in quest of disease","volume":"26","author":"Wasserstein","year":"2013","journal-title":"Semin. Dial."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.pharmthera.2008.08.008","article-title":"Carnitine in metabolic disease: Potential for pharmacological intervention","volume":"120","author":"Arduini","year":"2008","journal-title":"Pharmacol. Ther."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Merritt, J.L., Norris, M., and Kanungo, S. (2018). Fatty acid oxidation disorders. Ann. Transl. Med., 6.","DOI":"10.21037\/atm.2018.10.57"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1186\/s13023-014-0130-8","article-title":"Proposed guidelines for the diagnosis and management of methylmalonic and propionic acidemia","volume":"9","author":"Baumgartner","year":"2014","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Nasser, M., Javaheri, H., Fedorowicz, Z., and Noorani, Z. (2012). Carnitine supplementation for inborn errors of metabolism. Cochrane Database Syst. Rev., CD006659.","DOI":"10.1002\/14651858.CD006659.pub3"},{"key":"ref_108","first-page":"121","article-title":"Two siblings with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency suffered from rhabdomyolysis after l-carnitine supplementation","volume":"15","author":"Watanabe","year":"2018","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1042\/BCJ20160164","article-title":"Long-chain acylcarnitines determine ischaemia\/reperfusion-induced damage in heart mitochondria","volume":"473","author":"Liepinsh","year":"2016","journal-title":"Biochem. J."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Ferro, F., Ouill\u00e9, A., Tran, T.-A., Fontanaud, P., Bois, P., Babuty, D., Labarthe, F., and Le Guennec, J.-Y. (2012). Long-Chain Acylcarnitines Regulate the hERG Channel. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0041686"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1007\/s10545-009-1126-8","article-title":"Treatment recommendations in long-chain fatty acid oxidation defects: Consensus from a workshop","volume":"32","author":"Spiekerkoetter","year":"2009","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1007\/s11940-009-0046-0","article-title":"A Modern Approach to the Treatment of Mitochondrial Disease","volume":"11","author":"Parikh","year":"2009","journal-title":"Curr. Treat. Options Neurol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1002\/mus.20598","article-title":"Approaches to the treatment of mitochondrial diseases","volume":"34","author":"DiMauro","year":"2006","journal-title":"Muscle Nerve"},{"key":"ref_114","first-page":"130","article-title":"Marked elevation in plasma trimethylamine-N-oxide (TMAO) in patients with mitochondrial disorders treated with oral l-carnitine","volume":"15","author":"Vallance","year":"2018","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Janeiro, M.H., Ram\u00edrez, M.J., Milagro, F.I., Mart\u00ednez, J.A., and Solas, M. (2018). Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target. Nutrients, 10.","DOI":"10.3390\/nu10101398"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/18\/3251\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:17:33Z","timestamp":1760188653000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/18\/3251"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,6]]},"references-count":115,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2019,9]]}},"alternative-id":["molecules24183251"],"URL":"https:\/\/doi.org\/10.3390\/molecules24183251","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,6]]}}}