• The primary outcome of this study is the difference in percent body fat (%BF) between subjects with a long-chain fatty acid oxidation disorder and normal controls. [ Time Frame: December 2009 ] [ Designated as safety issue: No ]
  

• The secondary outcome of this study is the difference in weight gain between subjects with TFP and VLCAD deficiency consuming a high protein compared to a high carbohydrate diet for four months. [ Time Frame: December 2009 ] [ Designated as safety issue: No ]
  

Other: Dietary intervention
Subjects with trifunctional protein (TFP) or very long-chain acyl-CoA dehyrogenase (VLCAD) deficiency will be assigned to 4-months of increased protein, reduced carbohydrate diet or 4-months of current treatment with a high carbohydrate diet. The effect of MCT supplementation immediately prior to exercise will also be assessed in a randomized design.

A role for mitochondrial fatty acid oxidation in the peripheral signaling cascade of leptin, adiponectin and insulin has recently been proposed from animal studies but has not been investigated in humans. Children with trifunctional protein (TFP, including deficiency of long-chain hydroxyacyl-CoA dehydrogenase) and very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency, inherited disorders of long-chain fatty acid ß-oxidation, lack an ability to oxidize fatty acids for energy. They have increased levels of body fat and circulating leptin and a high incidence of obesity. Current therapy for children with these disorders is based on frequent meals and consuming a low fat, very high carbohydrate diet. Despite treatment, exercise induced rhabdomyolysis is a common complication of TFP and VLCAD deficiency that frequently leads to exercise avoidance. The effects of these genetic defects on body composition and weight regulation have not been investigated. The contribution of fatty-acid oxidation during moderate intensity exercise in children has also not been reported.

We propose to study peripheral signals of body weight regulation, body composition, and exercise metabolism in children with TFP and VLCAD deficiency compared to normal controls. We also propose to determine the effects of a long-term increased protein, low fat diet on body composition, and weight regulation in children with long-chain fatty acid oxidation disorders.