Summary: Carnitine deficiency is a secondary complication of many inborn errors of metabolism. Pharmacological treatment with carnitine not only corrects the deficiency, it facilitates removal of accumulating toxic acyl intermediates and the generation of mitochondrial free coenzyme A (CoA). The United States Food and Drug Administration (US FDA) approved the use of carnitine for the treatment of inborn errors of metabolism in 1992. This approval was based on retrospective chart analysis of 90 patients, with 18 in the untreated cohort and 72 in the treated cohort. Efficacy was evaluated on the basis of clinical and biochemical findings. Compelling data included increased excretion of disease-specific acylcarnitine derivatives in a dose–response relationship, decreased levels of metabolites in the blood, and improved clinical status with decreased hospitalization frequency, improved growth and significantly lower mortality rates as compared to historical controls. Complications of carnitine treatment were few, with gastrointestinal disturbances and odour being the most frequent. No laboratory or clinical safety issues were identified. Intravenous carnitine preparations were also approved for treatment of secondary carnitine deficiency. Since only 25% of enteral carnitine is absorbed and gastrointestinal tolerance of high doses is poor, parenteral carnitine treatment is an appealing alternative therapeutic approach. In 7 patients treated long term with high-dose weekly to daily venous boluses of parenteral carnitine through a subcutaneous venous port, benefits included decreased frequency of decompensations, improved growth, improved muscle strength and decreased reliance on medical foods with liberalization of protein intake. Port infections were the most troubling complication. Theoretical concerns continue to be voiced that carnitine might result in fatal arrhythmias in patients with long-chain fat metabolism defects. No published clinical studies substantiate these concerns. Carnitine treatment of inborn errors of metabolism is a safe and integral part of the treatment regime for these disorders.
Carnitine Free Carnitine Glutaric Aciduria Type Carnitine Supplementation Propionic Acidaemia
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.
Bohan TP, Helton E, McDonald I, et al (2001) Effect of L-carnitine treatment for valproate-induced hepatotoxicity. Neurology 56(10): 1405-1409.PubMedGoogle Scholar
Bonner CM, DeBrie KL, Hug G, et al (1995) Effects of parenteral L-carnitine supplementation on fat metabolism and nutrition in premature neonates. J Pediatr 126(2): 287-292.PubMedCrossRefGoogle Scholar
Bonnet D, Martin D, De Lonlay P, et al (1999) Arrhythmias and conduction defects as pre-senting symptoms of fatty acid oxidation disorders in children. Circulation 100(22): 2248-2253.PubMedGoogle Scholar
Colonna P, Illiceto S (2000) Myocardial infarction and left ventricular remodeling: results of the CEDIM trial. Carnitine Ecocardiografia Digitalizzata Infarto Miocardico. Am Heart J 139(2 Pt 3): S124-130.PubMedCrossRefGoogle Scholar
Corr PB, Yamada KA (1995) Selected metabolic alterations in the ischemic heart and their contributions to arrhythmogenesis. Herz20:156-168.PubMedGoogle Scholar
den Boer ME, Wanders RJ, Morris AA, et al (2002) Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: clinical presentation and follow-up of 50 patients. Pediatrics 109(1): 99-104.PubMedCrossRefGoogle Scholar
Helton E, Darragh R, Francis, P, et al (2000) Metabolic aspects of myocardial disease and a role for L-carnitine in the treatment of childhood cardiomyopathy. Pediatrics 105(6): 1260-1270.PubMedGoogle Scholar
Jackson S, Bartlett K, Land J, et al (1991) Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. Pediatr Res29: 406-441.PubMedGoogle Scholar
Lango R, Smolenski RT, Narkiewicz M, et al (2001) Influence of L-carnitine and its derivatives on myocardial metabolism and function in ischemic heart disease and during cardiopulmonary bypass. Cardiovasc Res 51(1): 21-29.PubMedCrossRefGoogle Scholar
Pons R, De Vivo DC (1995) Primary and secondary carnitine deficiency syndromes. J Child Neurol 10 (Supplement 2): S8-S24.PubMedGoogle Scholar
Rinaldo P, Yoon HR, Yu C, et al (1999) Sudden and unexpected neonatal death: a protocol for the postmortem diagnosis of fatty acid oxidation disorders. Semin Perinatol23: 204-210.PubMedCrossRefGoogle Scholar
Rocchiccioli F, Wanders RJA, Aubourg P, et al (1990) Deficiency of long-chain 3-hydroxyacyl-CoA dehydrogenase: a cause of lethal myopathy and cardiomyopathy in early childhood. Pediatr Res28: 657-662.PubMedGoogle Scholar
Shapira Y, Gutman A (1991) Muscle carnitine deficiency in patients using valproic acid. J Pediatr 118(4 Pt 1): 646-649.PubMedCrossRefGoogle Scholar
Siliprandi N (1986) Transport and function of carnitine: relevance to carnitine-deficient dis-eases. Ann NY Acad Sci 488: 118-126.PubMedGoogle Scholar
Tyni T, Palotie A, Viinikka L, et al (1997) Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency with the G1528C mutation: clinical presentation of 13 patients. J Pediatr130: 67-76.PubMedCrossRefGoogle Scholar
Winter SC, Szabo-Aczel S, Curry CJ, et al (1987) Plasma carnitine deficiency: clinical obser-vations in 51 pediatric patients. Am J Dis Child 141(6): 660-665.PubMedGoogle Scholar