eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Metabolic Diseases

Long-Chain Acyl CoA Dehydrogenase Deficiency: Treatment & Medication

Author: Fernando Scaglia, MD, FACMG, Associate Professor of Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine and Texas Children's Hospital
Contributor Information and Disclosures

Updated: Jul 22, 2009

Treatment

Medical Care

  • Evaluation for long-chain 3-hydroxy acyl-coenzyme A dehydrogenase (LCHAD) deficiency may be performed on an outpatient basis with acylcarnitine profile, serum free fatty acids, and urine organic acids; however, patients who are asymptomatic at the time of evaluation may not show abnormalities. If high index of suspicion exists on the basis of the history, a skin biopsy could be performed for fatty acid oxidation studies in fibroblasts. However, the availability of DNA studies (eg, sequencing and oligonucleotide-based array comparative genomic hybridization [CGH]) may supersede the need to start with fatty acid oxidation studies in cultured fibroblasts.
  • In cases of acute decompensation with unconfirmed diagnosis, collect samples during the acute episode while the hypoglycemia is corrected.
  • If the patient presents with acute hypoketotic hypoglycemic encephalopathy, the main goal is to secure sufficient energy intake by infusions of intravenous glucose.
  • The management of affected patients is directed at the avoidance of fasting. Most patients also are provided with uncooked cornstarch and medium-chain triglyceride (MCT) oil supplementation to further decrease exposure to fasting. Oral supplementation with docosahexanoic acid ethyl ester (DHA) may be considered to improve visual function. Consider carnitine supplementation if hypocarnitinemia is present; however, carnitine should not be used during acute decompensation.

Consultations

  • Genetic metabolic services
  • Nutritionist
  • Cardiologist
  • Ophthalmologist
  • Neurologist

Diet

  • A low-fat, high-carbohydrate diet with limited long-chain fatty acid intake (10% of total energy) is beneficial.
  • Addition of MCT-oil treatment (providing 10-20% of energy requirements) is reported to be beneficial with improvement in dicarboxylic aciduria and a normalization of the plasma level of long-chain acylcarnitines.
  • Coordinating MCT supplementation (0.5 g per kg of lean body mass) with periods of increased activity may improve the metabolic control of children with long-chain 3-hydroxy acyl-coenzyme A dehydrogenase and trifunctional protein deficiency following exercise.   
  • The use of uncooked cornstarch (2 g/kg/dose) at bedtime prevents early morning hypoglycemia after the overnight fast.
  • Supplementation with vegetable oils, as part of the 10% total long-chain fatty acid intake, provides essential fatty acids (ie, linoleic acid, linolenic acid) and prevents retinal disease, peripheral neuropathy, growth restriction, and dermatitis. Use of flax/walnut oils (containing the least amount of nonessential fatty acids) when compared to canola oil may reduce the accumulation of disease specific acyl-CoA intermediates, preventing peripheral neuropathy.
  • Prevention of fasting with frequent feeds is crucial.
  • DHA supplementation (100 mg/d) as some reports have demonstrated improvements of visual function with supplementation.
  • A daily multivitamin and mineral supplement that includes all fat-soluble vitamins is required.
  • Supplementation with heptanoate (C7) triglyceride has been evaluated for other long-chain fatty acid oxidation defects and has been suggested to be potentially useful for long-chain 3-hydroxy acyl-coenzyme A dehydrogenase deficiency; however, this advantage has not been clearly documented.
  • Because the incidence of obesity and overweight is increasing among children with long-chain 3-hydroxy acyl-coenzyme A dehydrogenase or trifunctional protein deficiency, a diet higher in protein and lower in carbohydrates may help to lower total energy intake and maintaining good metabolic control. However, long-term studies are needed in order to determine whether higher protein diets reduce risks of overweight and obesity.

Activity

  • Advise tempered activity when increased risk for rhabdomyolysis and myoglobinuria exists.
  • Advise avoidance of strenuous exercise activity and maintenance of adequate fluid intake to prevent dehydration with physical activity.
  • Advise restriction of activity when cardiomyopathy is present.

Medication

Try carnitine supplementation in patients with evident hypocarnitinemia and continue if symptoms improve; however, start carnitine supplementation with caution during acute fulminant symptoms because of the potential risk of cardiac arrhythmias.

Dietary supplements

L-carnitine at high doses corrects the metabolic abnormalities and hypocarnitinemia present in cases of long-chain 3-hydroxy acyl-coenzyme A dehydrogenase (LCHAD) deficiency. It may be important for the conjugation and excretion of fatty acids, for the enhancement of the excretion of toxic metabolites, and to generate free CoA; however, use with extreme caution during acute metabolic crises.


Levocarnitine (Carnitor)

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.
High doses are able to restore the level of free carnitine in plasma to normal, and many patients improve with this therapy; however, the concentration of long-chain acyl-carnitines increases, which can be detrimental and cause serious cardiac arrhythmias in fulminant crises.
Use in long-chain fatty acid oxidation disorders (eg, LCHAD deficiency, MTP deficiency) is a matter of continued debate, mainly during acute fulminant crises when it enhances the formation of long-chain acylcarnitines, which may cause ventricular arrhythmogenesis.

Adult

1 g/dose PO/IV tid; not to exceed 3 g/d

Pediatric

100-200 mg/kg/d PO divided bid/tid; not to exceed 3 g/d

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Do not use in acute metabolic crises; monitor blood chemistries, vital signs, plasma carnitine concentrations and overall clinical condition; in secondary carnitine deficiency, numerous metabolic disorders must be diagnosed correctly 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)

More on Long-Chain Acyl CoA Dehydrogenase Deficiency

Overview: Long-Chain Acyl CoA Dehydrogenase Deficiency
Differential Diagnoses & Workup: Long-Chain Acyl CoA Dehydrogenase Deficiency
Treatment & Medication: Long-Chain Acyl CoA Dehydrogenase Deficiency
Follow-up: Long-Chain Acyl CoA Dehydrogenase Deficiency
Multimedia: Long-Chain Acyl CoA Dehydrogenase Deficiency
References
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References

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Further Reading

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Keywords

long-chain acyl CoA dehydrogenase deficiency, LCHAD deficiency, trifunctional protein deficiency, hypoketotic hypoglycemia, vomiting, hypotonia, cardiomyopathy, sudden infant death, hepatic necrosis, cholestatic jaundice, hepatomegaly, cardiomegaly, cataracts, treatment, diagnosis

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Contributor Information and Disclosures

Author

Fernando Scaglia, MD, FACMG, Associate Professor of Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine and Texas Children's Hospital
Fernando Scaglia, MD, FACMG is a member of the following medical societies: American College of Medical Genetics, American Society of Human Genetics, Society for Inherited Metabolic Disorders, and Society for the Study of Inborn Errors of Metabolism
Disclosure: Nothing to disclose.

Medical Editor

Karl S Roth, MD, Professor and Chair, Department of Pediatrics, Creighton University School of Medicine
Karl S Roth, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American College of Nutrition, American Pediatric Society, American Society for Clinical Nutrition, American Society of Nephrology, Association of American Medical Colleges, Medical Society of Virginia, New York Academy of Sciences, Sigma Xi, Society for Pediatric Research, and Southern Society for Pediatric Research
Disclosure: MDS Pharma Salary Employment

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Margaret M McGovern, MD, PhD, Professor and Chair of Pediatrics, Stony Brook University, New York
Margaret M McGovern, MD, PhD is a member of the following medical societies: American Academy of Pediatrics and American Society of Human Genetics
Disclosure: Genzyme Grant/research funds PI

CME Editor

Paul D Petry, DO, FACOP, FAAP, Consulting Staff, Freeman Pediatric Care, Freeman Health System
Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association
Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD, Professor, Department of Pediatrics, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics, University of Nebraska Medical Center
Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association
Disclosure: Nothing to disclose.

 
 
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