Characterization of Biochemical Abnormalities Underlying Mitochondrial Dysfunction and Cardiomyopathy in Barth Syndrome and Adenine Nucleotide Translocase 1 (ANT-1) Deficiency

Principal Investigator: Yana Sandlers

The treatment of many inborn errors of metabolism is centered on recognizing and correcting, or compensating for metabolic aberrations. The limited understanding of the complexity of the biochemical aberrations in many of these disorders has hindered the ability of clinicians to compensate for the metabolic consequences. As a result, for many affected children the clinical course consists of a steady downward course starting in infancy and culminating in significant morbidity and or death. This proposal describes a plan to characterize the link between mitochondrial dysfunction and cardiomyopathy in Barth Syndrome and Adenine Nucleotide Translocase (ANT-1) deficiency. Since successful treatment in many inborn errors of metabolism centers around correcting biochemical deficiencies through substrate modification, an understanding of the complete biochemistry of these disorders is essential. We have recently had success in using small-scale studies to defining some of the mitochondrial biochemistry of Barth Syndrome and ANT-1 deficiency in identifying and describing abnormalities in the plasma amino acids and citric acid cycle intermediates. The goal of this work is to ultimately identify novel targets for treatment in the biochemically "untreatable" mitochondrial disorders Barth Syndrome and ANT-1 deficiency in order to improve clinical outcome and quality of life in affected individuals.