eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Metabolic Diseases
Carnitine Deficiency: Treatment & Medication
Updated: Jul 22, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
In infants with carnitine deficiency ascertained via newborn screen program, oral carnitine supplementation is followed by a slow increase of plasma carnitine levels. If the infants’ levels reflect maternal primary carnitine deficiency, the rise in plasma levels is fast and this should prompt the work-up towards the diagnosis of maternal primary carnitine deficiency. Guidelines for the management of carnitine deficiency and other fatty acid mitochondrial disorders have been established.7
- Evaluation for carnitine deficiency may be performed on an outpatient basis. In cases of acute decompensation, inpatient studies may be necessary in the acute phase and following stabilization of the patient.
- In acute situations, if the patient presents with hypoketotic hypoglycemic encephalopathy, insure stabilization with 10% dextrose in water at rates of 10 mg/kg/min intravenous (IV) initially; adjust infusion rate according to blood glucose concentrations.
- IV carnitine restores tissue carnitine concentrations for the transport of fatty acids in the mitochondria. This treatment removes toxic metabolites in the form of carnitine esters that are readily excreted in the urine. The use of IV carnitine should be considered only when the diagnosis of primary carnitine deficiency is entertained or confirmed. The use of IV carnitine in disorders of fatty acid oxidation in which long-chain acylcarnitines accumulate and have the potential of being arrhythmogenic is controversial. IV carnitine may be considered in cases of organic acidemias (eg, isovaleric acidemia, propionic acidemia, methylmalonic acidemia) when oral intake is not feasible.
- Consider pharmacological support for cardiomyopathy.
- Medical therapy with oral carnitine in primary carnitine deficiency improves fasting ketogenesis, cardiac function, growth, and cognitive performance.
- Direct the therapy in secondary carnitine deficiency to replenish carnitine and treat the primary metabolic defect with specific diet and other supplements, such as riboflavin, glycine, or biotin.
Consultations
- Genetic metabolic services
- Nutritionist
Diet
- Patients with primary carnitine deficiency requires no special diet as long as they are taking carnitine supplementation and are not faced with situations of stress and starvation.
- Patients with fatty acid oxidation disorders require a high-carbohydrate fat-restricted diet (30% calories from fat) and must eat frequently.
- Prescribe medium-chain triglyceride supplementation in patients with long-chain fatty acid disorders.
- Advise use of uncooked cornstarch at bedtime to prevent early morning hypoglycemia after the overnight fast.
- Supplementation of essential fatty acids (ie, linoleic acids, linolenic acids) prevents the growth restriction and dermatitis that are associated with fatty acid deficiency.
- Consider specific protein-restricted diets in patients with aminoacidopathies and organic acidemias associated with secondary carnitine deficiency.
Activity
- Once carnitine supplementation has been instituted for primary carnitine deficiency, cardiac function, strength, and growth improve significantly. No specific recommendations to limit physical activity are indicated if the cardiomyopathy has reverted.
- Secondary carnitine deficiency caused by fatty acid oxidation disorders may require tempered or restricted activity in certain cases, including the following:
- Conditions associated with increased risk for rhabdomyolysis and myoglobinuria (eg, carnitine palmitoyltransferase II [CPT-II] deficiency, very long-chain acyl-CoA dehydrogenase [VLCAD] deficiency)
- Conditions in which a cardiomyopathy is present (eg, long-chain 3-hydroxyacyl-CoA dehydrogenase [LCHAD] deficiency, VLCAD deficiency)
- Strenuous exercise or activity should be avoided, and frequent snacks and good hydration should be procured with physical activity.
Medication
Use of L-carnitine in primary carnitine deficiency restores plasma carnitine levels to nearly normal, but muscle carnitine levels rise slightly. Muscle function can be normalized in patients with carnitine deficiency when muscle carnitine levels remain less than 10% of controls. Cardiomyopathy often responds well to carnitine supplementation. Carnitine supplementation in fatty acid oxidation disorders and other organic acidurias is to correct carnitine deficiency and to allow removal of toxic intermediates. The other goal of therapy is to restore CoA levels. Carnitine therapy for long-chain fatty acid oxidation defects has become questionable because it promotes formation of long-chain acylcarnitines that may cause arrhythmogenesis and membrane dysfunction. Carnitine supplementation in total parenteral nutrition (TPN) prevents secondary carnitine deficiency in preterm newborns.
Dietary supplements
At high doses, L-carnitine corrects severe carnitine depletion and associated metabolic abnormalities observed in primary carnitine deficiency and enables the production of ketone bodies during fasting. In secondary carnitine deficiency, carnitine enhances excretion of toxic metabolites and generation of free CoA.
Levocarnitine (Carnitor, L-Carnitine)
An amino acid derivative synthesized from methionine and lysine, required in energy metabolism. Can promote excretion of excess fatty acids in patients with defects in fatty acid metabolism or specific organic acidopathies, which bioaccumulate acyl CoA esters. Normal levels occur in liver, and mild level increases occur in skeletal muscle. May cause reversal of skeletal and heart muscle abnormalities.
Adult
1 g PO/IV tid; not to exceed 3 g/d
Pediatric
50 mg/kg/d PO initially; may gradually increase to 100-400 mg/kg/d PO divided bid/tid; not to exceed 3 g/d
None reported
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Monitor blood chemistries, vital signs, plasma carnitine concentrations and overall clinical condition; in secondary carnitine deficiency, a number of metabolic disorders must be correctly diagnosed before initiation of carnitine supplementation; use in long-chain fatty acid oxidation defects (eg, LCHAD deficiency, trifunctional protein deficiency, VLCAD deficiency) may enhance formation of long-chain acylcarnitines which may cause ventricular arrhythmogenesis; adverse effects with toxic doses are nausea, vomiting, diarrhea, and a fish odor derived from a metabolite of carnitine (trimethylamine)
Dextrose 10% (D10W, D-glucose)
Monosaccharide absorbed from intestines and distributed, stored, and used by tissues.
Parenterally injected dextrose is used in patients unable to sustain adequate PO intake. Direct PO absorption results in a rapid increase in blood glucose concentrations. Dextrose is effective in small doses. Concentrated dextrose infusions provide higher amounts of glucose and increased caloric intake in a small volume of fluid.
Adult
10 mg/kg/min IV initially; adjust infusion rate according to blood glucose concentrations
Pediatric
Administer as in adults
Caution when administering parenteral fluids to patients receiving corticosteroids or corticotropin, especially if the solution contains sodium ions
Avoid in diabetic coma if blood sugar levels are extremely high and in severely dehydrated patients; avoid administration in intraspinal or intracranial hemorrhage; avoid in dehydrated patients with delirium tremens, hepatic coma, or glucose-galactose malabsorption syndrome
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May cause nausea, which also may occur with hypoglycemia; IV dextrose solutions may result in dilution of serum electrolyte concentrations or overhydration if fluid overload is present
Caution in congestion or pulmonary edema; hypertonic dextrose given peripherally may cause thrombosis (administer through central venous catheter); caution in subclinical diabetes mellitus or carbohydrate intolerance; risk of inducing significant hyperglycemia or hyperosmolar syndrome is increased if solution is administered rapidly, especially in patients with chronic uremia or carbohydrate intolerance
Do not administer concentrated solutions SC/IM; rates of dextrose infusion >0.5 g/kg/h may produce glycosuria; monitor fluid balance, electrolyte concentrations, and acid-base balance closely; dextrose administration may produce vitamin B-complex deficiency
Riboflavin (Vitamin B-2)
Essential in activation of pyridoxine and conversion of tryptophan to niacin; component of flavoprotein enzymes, which are necessary for tissue respiration. Riboflavin functions as a cofactor for electron transport in complex I, complex II, and in the electron transfer of flavoprotein. It has proven useful for the treatment of some patients with SCAD deficiency, riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency, and milder forms of glutaric aciduria type II.
Adult
400 mg/d PO
Pediatric
100 mg/d PO
Probenecid decreases absorption
None reported
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Pregnancy category C if dose exceeds RDA; riboflavin deficiency often occurs in the presence of other B vitamin deficiencies; large dose may turn urine bright yellow
Betaine (Cystadane)
Methyl group donor used in the treatment of homocystinuria. Decreases elevated homocysteine blood levels. Used for conditions that can cause hyperhomocysteinemia and secondary carnitine deficiency (ie, cobalamin C deficiency).
Adult
3 g PO bid; not to exceed 20 g/d
Pediatric
<3 years: 100 mg/kg/d PO initially; increase weekly by 100 mg/kg
>3 years: Administer as in adults
None reported
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May cause GI distress (eg, nausea, diarrhea)
Hydroxocobalamin (Vitamin B-12, Hydro cobex)
Deoxyadenosylcobalamin and hydroxocobalamin are active forms of vitamin B-12 in humans. Vitamin B-12 synthesized by microbes but not humans or plants. Vitamin B-12 deficiency may result from intrinsic factor deficiency (pernicious anemia), partial or total gastrectomy, or diseases of the distal ileum. Used to treat conditions caused by altered cobalamin metabolism that may cause secondary carnitine deficiency (ie, cobalamin C deficiency).
Adult
Maintenance: 1 mg IM qd initially; may adjust dose and administration frequency as symptoms allow
Pediatric
Administer as in adults
Aminosalicylic acid may decrease biologic and therapeutic action; chloramphenicol may decrease hematologic effects; excessive alcohol and colchicine may cause malabsorption
Documented hypersensitivity; hypersensitivity to cobalt; hereditary optic nerve atrophy
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Administer IM only; anaphylactic shock and death have occurred after parenteral vitamin B-12 administration; give intradermal test dose in patients sensitive to cobalamins; antibody formation may occur to the hydroxocobalamin-transcobalamin complex; may rapidly (ie, within 48 h) cause severe hypokalemia
Ubidecarenone (CoQ-10, Coenzyme Q, Ubiquinone)
Coenzyme involved in mitochondrial energy production. Controls flow of oxygen within individual cells. Has essential antioxidant and membrane-stabilizing properties.
Adult
100 mg PO qd
Pediatric
4.3 mg/kg/d PO divided bid/tid
Decreases effectiveness of warfarin
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Because of complexities related to absorption, levels can be helpful in optimizing the dose; this hydrophobic compound can be dissolved in vegetable oil to make a liquid for those unable to swallow
Glycine (Aminoacetic acid)
The simplest amino acid that helps improve glycogen storage is used in the synthesis of hemoglobin, collagen, and glutathione, and it facilitates the amelioration of high blood fat and uric acid levels. Glycine is primarily used for the treatment of isovaleric acidemia, which is an organic acidemia that causes secondary carnitine depletion.
Adult
250 mg/kg/d PO divided tid
Pediatric
Administer as in adults
None reported
Documented hypersensitivity; anuria
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May cause hemolytic anemia, thrombocytopenia, hypotension, bradycardia, ECG changes, electrolyte and CNS (including visual) changes alterations
Biotin
Water-soluble vitamin, generally classified as a B-complex vitamin. An essential coenzyme in fat metabolism and in other carboxylation reactions. Used for the treatment of biotin responsive propionic acidemia, which can lead to secondary carnitine deficiency.
Adult
10 mg PO qd
Pediatric
Administer as in adults
Primidone and carbamazepine inhibit absorption in small intestine; phenobarbital, phenytoin, and carbamazepine increase urinary excretion; long-term treatment with sulfa drugs or other antibiotics may decrease bacterial synthesis, potentially increasing the requirement for dietary biotin.
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
None reported
More on Carnitine Deficiency |
| Overview: Carnitine Deficiency |
| Differential Diagnoses & Workup: Carnitine Deficiency |
 Treatment & Medication: Carnitine Deficiency |
| Follow-up: Carnitine Deficiency |
| References |
| « Previous Page | Next Page » |
References
Koizumi A, Nozaki J, Ohura T, et al. Genetic epidemiology of the carnitine transporter OCTN2 gene in a Japanese population and phenotypic characterization in Japanese pedigrees with primary systemic carnitine deficiency. Hum Mol Genet. Nov 1999;8(12):2247-54. [Medline].
Schimmenti LA, Crombez EA, Schwahn BC, Heese BA, Wood TC, Schroer RJ. Expanded newborn screening identifies maternal primary carnitine deficiency. Mol Genet Metab. Apr 2007;90(4):441-5. [Medline].
Wilcken B, Wiley V, Sim KG, Carpenter K. Carnitine transporter defect diagnosed by newborn screening with electrospray tandem mass spectrometry. J Pediatr. Apr 2001;138(4):581-4. [Medline].
Vijay S, Patterson A, Olpin S, Henderson MJ, Clark S, Day C. Carnitine transporter defect: diagnosis in asymptomatic adult women following analysis of acylcarnitines in their newborn infants. J Inherit Metab Dis. Oct 2006;29(5):627-30. [Medline].
Wattanasirichaigoon D, Khowsathit P, Visudtibhan A, Suthutvoravut U, Charoenpipop D, Kim SZ. Pericardial effusion in primary systemic carnitine deficiency. J Inherit Metab Dis. Aug 2006;29(4):589. [Medline].
Amat di San Filippo C, Taylor MR, Mestroni L, Botto LD, Longo N. Cardiomyopathy and carnitine deficiency. Mol Genet Metab. Jun 2008;94(2):162-6. [Medline].
Angelini C, Federico A, Reichmann H, Lombes A, Chinnery P, Turnbull D. Task force guidelines handbook: EFNS guidelines on diagnosis and management of fatty acid mitochondrial disorders. Eur J Neurol. Sep 2006;13(9):923-9. [Medline].
Angelini C, Vergani L, Martinuzzi A. Clinical and biochemical aspects of carnitine deficiency and insufficiency: transport defects and inborn errors of beta-oxidation. Crit Rev Clin Lab Sci. 1992;29(3-4):217-42. [Medline].
Bok LA, Vreken P, Wijburg FA, et al. Short-chain Acyl-CoA dehydrogenase deficiency: studies in a large family adding to the complexity of the disorder. Pediatrics. Nov 2003;112(5):1152-5. [Medline].
Bonner CM, DeBrie KL, Hug G, Landrigan E, Taylor BJ. Effects of parenteral L-carnitine supplementation on fat metabolism and nutrition in premature neonates. J Pediatr. Feb 1995;126(2):287-92. [Medline].
Borum PR. Carnitine in neonatal nutrition. J Child Neurol. Nov 1995;10 Suppl 2:S25-31. [Medline].
De Vivo D, Tein I. Primary and secondary disorders of carnitine metabolism. International Pediatrics. 1990;5:134-41.
Lamhonwah AM, Olpin SE, Pollitt RJ, et al. Novel OCTN2 mutations: no genotype-phenotype correlations: early carnitine therapy prevents cardiomyopathy. Am J Med Genet. Aug 15 2002;111(3):271-84. [Medline].
Longo N, Amat di San Filippo C, Pasquali M. Disorders of carnitine transport and the carnitine cycle. Am J Med Genet C Semin Med Genet. May 15 2006;142C(2):77-85. [Medline].
Pons R, De Vivo DC. Primary and secondary carnitine deficiency syndromes. J Child Neurol. Nov 1995;10 Suppl 2:S8-24. [Medline].
Rinaldo P, Raymond K, al-Odaib A, Bennett MJ. Clinical and biochemical features of fatty acid oxidation disorders. Curr Opin Pediatr. Dec 1998;10(6):615-21. [Medline].
Rinaldo P, Stanley CA, Hsu BY, Sanchez LA, Stern HJ. Sudden neonatal death in carnitine transporter deficiency. J Pediatr. Aug 1997;131(2):304-5. [Medline].
Roe C, Coates P. Mitochondrial fatty acid oxidation disorders. In: Scriver CR, et al, eds. The Metabolic and Molecular Basic of Inherited Disease. 7th ed. New York, NY: McGraw-Hill, Health Professions Division;.; 1995:1501-1533.
Saudubray JM, Martin D, de Lonlay P, et al. Recognition and management of fatty acid oxidation defects: a series of 107 patients. J Inherit Metab Dis. Jun 1999;22(4):488-502. [Medline].
Scaglia F, Longo N. Primary and secondary alterations of neonatal carnitine metabolism. Semin Perinatol. Apr 1999;23(2):152-61. [Medline].
Scaglia F, Wang Y, Longo N. Functional characterization of the carnitine transporter defective in primary carnitine deficiency. Arch Biochem Biophys. Apr 1 1999;364(1):99-106. [Medline].
Stanley CA. Carnitine deficiency disorders in children. Ann NY Acad Sci. 2004;1003:42-51.
Further Reading
Keywords
carnitine deficiency, CD, primary carnitine deficiency, maternal carnitine deficiency, expanded newborn screening, myopathic carnitine deficiency, secondary carnitine deficiency, carnitine deficiency limited to the muscle, primary systemic carnitine deficiency, lipid-storage disease
lipid metabolism disorder, L-carnitine, hydrophilic amino acid derivative, progressive cardiomyopathy, hypoglycemia hypoketotic encephalopathy, fatty acid oxidation disorders, organic acidemias, ventricular fibrillation, ventricular tachycardia, heart failure, dilated cardiomyopathy, medium-chain acyl-CoA dehydrogenase deficiency, MCAD deficiency, heart myopathy, skeletal myopathy, hepatomegaly, hyperammonemia, gastrointestinal dysmotility, lipid storage myopathy, renal Fanconi tubulopathy
valproic acid, fulminant liver failure, Reye syndrome, pigmentary retinopathy, peripheral neuropathy, cardiac arrhythmias, myoglobinuria, glutaric aciduria type II deficiency, carnitine palmitoyltransferase II deficiency, CPT-II deficiency, mid-facial hypoplasia, frontal bossing, Zellwegerlike phenotype, congenital abnormalities of the abdominal wall, Fanconi syndrome, Lowe syndrome, cystinosis, lysinuric protein intolerance, propionic acidemia
methylmalonic acidemia, aminoacidopathies, isovaleric acidemia, propionic acidemia, methylmalonic acidemia, glutaric acidemia type I, 3-hydroxymethylglutaryl-CoA lyase deficiency, urea cycle defects, ornithine transcarbamylase deficiency, carbamoyl phosphate synthetase deficiency, X-linked oculocerebrorenal syndrome, chronic renal failure, cirrhosis, lacto-ovo–vegetarian diet, malabsorption syndromes, valproate, pivampicillin, emetine, zidovudine
