Context: Long Chain 3-hydroxyacyl-CoA Dehydrogenase Deficiency (LCHADD) is a rare autosomal recessive defect of mitochondrial fatty acid oxidation. An estimated 40 - 50 people are alive in the United States with LCHADDI. Current standard medical nutrition therapy consists of dietary therapy with a high carbohydrate, low long-chain fatty acid diet, in addition to medium chain triglyceride supplementation, avoidance of fasting and physical activity. Current treatment has reduced the acute symptoms of LCHADD, including fasting induced hypoketotic hypoglycemia, lactic acidosis, hypertrophic cardiomyopathy, liver dysfunction and coma. However, current dietary therapy has not reduced the long term consequences which include pigmentary retinopathy, peripheral neuropathy and recurrent rabdomyolysis. Additionally, 40% of LCHADD patients followed at OHSU are obese or overweight. While this disorder was first described in 1990, no systematic research has been conducted on the optimal dietary treatment of LCHADD. It is proposed that the combination of avoidance of fasting, physical activity and consumption of a high carbohydrate diet promotes a state of chronic anabolism in these children,· leading to excessive lipid synthesis and storage, an increased risk of obesity and diminished metabolic control of LCHAD deficiency.
Objective: To determine if a high protein, reduced carbohydrate diet will decrease whole body anabolism and improve metabolic control compared to the standard LCHADD diet.
Design: The metabolic response of a high protein, reduced carbohydrate diet compared,ta: the standard LCHADD diet was assessed in a random crossover design.
Setting: Five children with LCHADD were recruited from a cohort of 13 children with LCHADD participating in an ongoing trial examining retinal degeneration. Subjects traveled to OHSU and were admitted to the inpatient General Clinical Research Center (GCRC) unit for the protocol.
Procedure: In a randomized design, patients were fed a standard LCHADD diet for 7 days and a high protein, reduced carbohydrate diet for 7 days.
Outcome Measures: Body composition at admission, daily dietary intake, indirect calorimetry (showing resting energy expenditure (REE), and substrate utilization), and Blood levels of plasma acylcarnitines obtained twice and compared between diet periods were measured.
Data Analysis: Results of each 7 day diet period were compared using a paired T -test with a P value.:5 0.05 considered statistically significant.
Results: 20% of the subject population was obese. Patients self-selected 7% fewer calories during the high protein phase. Nutrient composition the research diets consumed was very close to study design. There was increased frequency and magnitude of resting lipogenesis during the high carbohydrate phase. There was no significant lipid oxidation during the high protein phase. Fasting acy1carnitine levels showed a trend towards higher levels during the high protein phase. Acylcarnitine levels during the meal tolerance testing showed no significant variation in AUC.
Conclusion: Increased dietary protein in children with LCHAD deficiency led to a reduction of self selected calories consumed without significant increase in lipid oxidation. However, there was a trend toward increased fasting hydroxyacy1carnitines with increased dietary protein.
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