This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Barth Syndrome is an X-linked disorder characterized by dilated cardiomyopathy, cyclic neutropenia, skeletal myopathy, and growth deficiency. Clinical disease expression is variable, even within families. Mutations in the TAZ gene at Xq28 are responsible, leading to cardiolipin deficiency and mitochondrial dysfunction. To date there has been no systematic evaluation of the cardiac phenotype. Recent unpublished reports suggest an increased incidence of arrhythmia, especially among adolescents and young adults. This proposal is an observational study of a cohort of patients with Barth syndrome designed to evaluate the age-related risk of arrhythmia in addition to investigating the relationships of cardiac performance, skeletal myopathy, and biochemical correlates of disease severity. The hypothesis is that an age-related risk of cardiac rhythm disturbance is present and independent of the severity of cardiomyopathy. Secondarily, the degree of cardiac dysfunction may be related to other variables including neutropenia, carnitine profile, and degree of skeletal myopathy. This proposal seeks to confirm the hypothesis through two specific aims.
The first aim will address analysis of cardiac rhythm abnormalities and the second aim will investigate the cardiomyopathy using detailed echocardiographic analysis and compare cardiac performance to skeletal myopathy and biochemical and hematological variables including white blood cell count, carnitine level, and cholesterol. We anticipate that the results of this study will be valuable in guiding the medical care of patients with Barth Syndrome, including screening for arrhythmias and the potential need for medical or device therapy for cardiac rhythm disturbance.
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