Barth Syndrome: Connecting Cardiolipin to Cardiomyopathy

摘要: The Barth syndrome (BTHS) is caused by an inborn error of metabolism that manifests characteristic phenotypic features including altered mitochondrial membrane phospholipids, lactic acidosis, organic acid-uria, skeletal muscle weakness and cardiomyopathy. underlying cause BTHS has been definitively traced to mutations in the tafazzin (TAZ) gene locus on chromosome X. TAZ encodes a phospholipid transacylase promotes cardiolipin acyl chain remodeling. Absence activity results molecular species heterogeneity, increased levels monolysocardiolipin lower abundance. In cardiac tissue mitochondria these alterations perturb inner membrane, compromising electron transport function aerobic respiration. Decreased flow from fuel via NADH ubiquinone oxidoreductase leads buildup matrix space product inhibition key TCA cycle enzymes. As slows pyruvate generated glycolysis diverted acid. turn, Cori increases supply with glucose for continued ATP production. Acetyl CoA unable enter acid waste products are excreted urine. Overall, reduced production efficiency exacerbated under conditions energy demand. Prolonged deficiency capacity underlies cell pathology ultimately manifest as dilated