Carnitine supplementation for inborn errors of metabolism

Abstract

There are no published or ongoing randomised controlled clinical trials relevant to this review question. Therefore, in the absence of any high level evidence, clinicians should base their decisions on clinical experience and in conjunction with preferences of the individual where appropriate. This does not mean that carnitine is ineffective or should not be used in any inborn error of metabolism. However, given the lack of evidence both on the effectiveness and safety of carnitine and on the necessary dose and frequency to be prescribed, the current prescribing practice should continue to be observed and monitored with care until further evidence is available. Methodologically sound trials, reported according to the Consolidated Standards of Reporting Trials (CONSORT) statement, are required. It should be considered whether placebo-controlled trials in potentially lethal diseases, e.g. carnitine transporter disorder or glutaric aciduria type I, are ethical.

Three novel variants identified in genes causing Isobutyryl-CoA dehydrogenase deficiency in seven unrelated Chinese families

“…Management of affected individuals must be highly individualized. For all confirmed cases, particularly those who are currently asymptomatic, avoiding catabolic stress (prolonged fasting, strenuous exercise, or excessive fatigue) is essential to prevent metabolic decompensation [19][20]. Patients with evidence of significant free carnitine deficiency should receive prompt L-carnitine supplementation to restore normal carnitine homeostasis.…”

Three novel variants identified in genes causing Isobutyryl-CoA dehydrogenase deficiency in seven unrelated Chinese families

“…Management of affected individuals must be highly individualized. For all confirmed cases, particularly those who are currently asymptomatic, avoiding catabolic stress (prolonged fasting, strenuous exercise, or excessive fatigue) is essential to prevent metabolic decompensation [19][20]. Patients with evidence of significant free carnitine deficiency should receive prompt L-carnitine supplementation to restore normal carnitine homeostasis.…”

Novel ACAD8 variants identified in Isobutyryl-CoA dehydrogenase deficiency: challenges in phenotypic variability and management

“…L-carnitine supplementation is integral to IBDD management, facilitating the excretion of toxic isobutyryl-CoA intermediates and preventing secondary carnitine depletion ( Nasser et al, 2012 ). In this study, six of seven patients received oral L-carnitine (50 mg/kg/day), with no reported adverse effects.…”

Do renal and cardiac malformations in the fetus signal carnitine palmitoyltransferase II deficiency? A rare lethal fatty acid oxidation defect

“…Carnitine supplementation remains the mainstay in primary carnitine deficiency. Cochrane review concluded that there is a lack of evidence-based data on the efficacy and safety of carnitine supplements in IEM 27. In mouse models, there was inhibition of oxidative phosphorylation in the mitochondria of the ischaemic myocardium due to LCAC accumulation 28.…”

Three novel variants identified in genes causing Isobutyryl-CoA dehydrogenase deficiency in seven unrelated Chinese families

“…Management of affected individuals must be highly individualized. For all confirmed cases, particularly those who are currently asymptomatic, avoiding catabolic stress (prolonged fasting, strenuous exercise, or excessive fatigue) is essential to prevent metabolic decompensation [19][20]. Patients with evidence of significant free carnitine deficiency should receive prompt L-carnitine supplementation to restore normal carnitine homeostasis.…”

Novel ACAD8 variants identified in Isobutyryl-CoA dehydrogenase deficiency: challenges in phenotypic variability and management

“…L-carnitine supplementation is integral to IBDD management, facilitating the excretion of toxic isobutyryl-CoA intermediates and preventing secondary carnitine depletion ( Nasser et al, 2012 ). In this study, six of seven patients received oral L-carnitine (50 mg/kg/day), with no reported adverse effects.…”

Do renal and cardiac malformations in the fetus signal carnitine palmitoyltransferase II deficiency? A rare lethal fatty acid oxidation defect

“…Carnitine supplementation remains the mainstay in primary carnitine deficiency. Cochrane review concluded that there is a lack of evidence-based data on the efficacy and safety of carnitine supplements in IEM 27. In mouse models, there was inhibition of oxidative phosphorylation in the mitochondria of the ischaemic myocardium due to LCAC accumulation 28.…”

Three novel variants identified in genes causing Isobutyryl-CoA dehydrogenase deficiency in seven unrelated Chinese families

“…Management of affected individuals must be highly individualized. For all confirmed cases, particularly those who are currently asymptomatic, avoiding catabolic stress (prolonged fasting, strenuous exercise, or excessive fatigue) is essential to prevent metabolic decompensation [19][20]. Patients with evidence of significant free carnitine deficiency should receive prompt L-carnitine supplementation to restore normal carnitine homeostasis.…”

Novel ACAD8 variants identified in Isobutyryl-CoA dehydrogenase deficiency: challenges in phenotypic variability and management

“…L-carnitine supplementation is integral to IBDD management, facilitating the excretion of toxic isobutyryl-CoA intermediates and preventing secondary carnitine depletion ( Nasser et al, 2012 ). In this study, six of seven patients received oral L-carnitine (50 mg/kg/day), with no reported adverse effects.…”

Do renal and cardiac malformations in the fetus signal carnitine palmitoyltransferase II deficiency? A rare lethal fatty acid oxidation defect

“…Carnitine supplementation remains the mainstay in primary carnitine deficiency. Cochrane review concluded that there is a lack of evidence-based data on the efficacy and safety of carnitine supplements in IEM 27. In mouse models, there was inhibition of oxidative phosphorylation in the mitochondria of the ischaemic myocardium due to LCAC accumulation 28.…”