eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Metabolic Diseases
Long-Chain Acyl CoA Dehydrogenase Deficiency: Treatment & Medication
Updated: Jul 22, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
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
None known
Documented hypersensitivity
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
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
Treatment & Medication: Long-Chain Acyl CoA Dehydrogenase Deficiency