232. Short_Term, In Vivo Correction of VLCAD Deficiency in Mice: Steps toward a Gene Therapy for Cardiomyopathy

Cardiomyopathy is an important cause of morbidity and mortality in children. Deficiency of very-long-chain acyl-CoA dehydrogenase (VLCAD), one of several nuclear encoded mitochondrial enzymes that catalyze the initial step in the beta-oxidation of straight chain fatty acids, often presents with cardiomyopathy and/or sudden death. How VLCAD deficiency causes cardiomyopathy is unclear, but appears to be related to the accumulation of toxic long-chain acyl-carnitine species rather than a block in energy metabolism. A recent report of a 5-year-old with VLCAD deficiency note resolution of her hypertrophic cardiomyopathy while on a strict low fat diet supplemented with medium chain triglycerides and carnitine. While dietary therapy for VLCAD deficiency has been beneficial to some, many people to not respond. Intercurrent illness with diminished oral intake, exercise, or fasting all increase demand for fatty acid metabolism and can potentially trigger catastrophic events even while on dietary therapy.