The cardiomyopathy of Friedreich's ataxia
Heart disease (“cardiomyopathy”) is very common in patients with Friedreich’s ataxia (FRDA) and is often the cause of death. The “ejection fraction” of the left heart chamber (ventricle) declines as the disease progresses and ultimately does not meet the demands of organs such as kidney and brain. Heart disease in FRDA advances independently of the nervous system disorder (ataxia). This research focuses on the role of iron in FRDA in the main “working” heart muscle and the cardiac conduction system. This system consists of specialized muscle fibers that deliver excitatory impulses to all chambers of the heart. Normally, right and left ventricular walls and interventricular septum contract in synchrony to generate a powerful heart beat. The triggering impulses travel in two steps from the sinoatrial node in the right antechamber (atrium) to the atrioventricular node at the junction of atria and ventricles. From the atrioventricular node, additional unique fibers constituting the “bundle of His” conduct impulses in a rhythmic fashion to the main heart muscles. Friedreich’s ataxia is due to an inherited loss of a small protein, “frataxin” (named after Friedreich’s ataxia). The hypothesis is that frataxin deficiency causes diffuse or localized iron excess in the heart; and that the metal is toxic to the main "working" heart muscle fibers and the cardiac conduction system. The investigation will use heart tissues of deceased patients with FRDA whose families have donated organs for FRDA research. The two main methods are (1) X-ray fluorescence of heart tissue to detect and measure iron in the main muscles and the fibers of the conduction system; and (2) advanced slide techniques to visualize iron, the iron-responsive proteins ferritin and mitochondrial ferritin, and proteins of the conduction system. The clinical relevance is insight into iron in FRDA cardiomyopathy to improve decision-making about the potential benefit of chelation therapy.