Medical Care
Patients with LCHAD deficiency may have normal growth and development with early appropriate treatment. [35]
Evaluation for 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
See the list below:
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Genetic metabolic services
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Nutritionist
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Cardiologist
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Ophthalmologist
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Neurologist
Diet
A low-fat, high-carbohydrate diet with limited long-chain fatty acid intake (10% of total energy) is usually recommended. However, short-term higher-protein diets were shown to be safe and well-tolerated by overweight and obese children with LCAD deficiency. These patients benefited from the lowered energy intake and increased energy expenditure compared to a standard high-carbohydrate diet. [36]
Addition of medium-chain triglycerides (MCT) 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 LCHAD 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. [37] 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. [38]
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 LCHAD deficiency; however, this advantage has not been clearly documented.
Because the incidence of obesity and overweight is increasing among children with LCHAD 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 in patients at an increased risk for rhabdomyolysis and myoglobinuria.
Advise that coordinating MCT supplementation with periods of increased activity may improve metabolic control following exercise. [39]
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.
Prevention
Prevent fasting with frequent feeds and use of uncooked cornstarch to avoid episodes of hypoglycemia.
Aggressively treat infections and fever to prevent a catabolic state.
Advise a fat-restricted diet with high-carbohydrate content. Triacylglycerols should provide less than 10-15% of the patient's total energy supply. Supplementation of dietary fat with medium-chain fatty acids is necessary.
Use docosahexanoic acid to prevent retinal degeneration.
Ensure carnitine supplementation in patients with documented secondary carnitine deficiency, especially if it contributes to alleviation of symptoms.
Advise avoidance of exercise and dehydration with hot temperatures because rhabdomyolysis and myoglobinuria may occur with LCHAD deficiency.
Screening for LCHAD deficiency should be performed in newborns from mothers with hepatic complications during pregnancy such as acute fatty liver of pregnancy or severe hemolytic anemia, elevated liver enzymes, low platelet count (HELLP) syndrome.
Further Outpatient Care
Aggressively treat infections and fever to prevent a catabolic state.
Carefully review diet compliance regarding avoidance of fasting, compliance with fat-restricted diet, supplementation of uncooked cornstarch, and intake of medium-chain triglyceride (MCT) oil.
Monitor carnitine levels and determine if carnitine supplementation is required.
Refer patient for ophthalmological evaluation for possible pigmentary retinopathy. All of these subjects should have a baseline ophthalmological evaluation within the first month of diagnosis and annual follow-ups. Fundus photography and repeated electroretinography examinations should be performed.
Conduct a neurological evaluation with nerve conduction studies to assess for possible peripheral neuropathy.
Further Inpatient Care
Admit patients with LCHAD deficiency for medical management of acute hypoketotic hypoglycemic encephalopathy. Dextrose (10%) at rates of 10 mg/kg/min or greater may be required to achieve normoglycemia. Do not estimate rate of intravenous (IV) glucose infusion on blood glucose levels alone. In principle, use IV carnitine only in cases of documented severe secondary carnitine deficiency. Carnitine therapy in long-chain fatty acid oxidation disorders is in question because it promotes long-chain acylcarnitine formation, and these acylcarnitines may cause ventricular arrhythmogenesis. Carefully monitor liver transaminases because acute hepatic dysfunction may accompany the metabolic crises.
Admit patient for management of rapidly evolving cardiomyopathy that may or may not be associated with the hypoglycemic crises.
Admit patient for management of severe rhabdomyolysis and myoglobinuria to prevent renal failure.
Inpatient & Outpatient Medications
Medications include L-carnitine, which should be tried in patients with evident hypocarnitinemia and should be continued if it ameliorates the symptoms. Use with caution during acute episodes because L-carnitine could potentially trigger cardiac arrhythmias.
Transfer
If diagnosis of LCHAD deficiency is suspected but workup facilities are inadequate and no metabolic specialists are available, transfer of patient to a tertiary care hospital for further workup and management may be necessary.
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Schematic demonstrating mitochondrial fatty acid beta-oxidation and effects of long-chain acyl CoA dehydrogenase deficiency (LCHAD) deficiency.
