CARDIAC AND SKELETAL MUSCLE IN BARTH SYNDROME

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 Barth综合征是一种X连锁疾病，以扩张型心肌病、周期性中性粒细胞减少、骨骼肌病和生长缺陷为特征。临床疾病的表现是多种多样的，即使在家庭内部也是如此。Xq28的TAZ基因突变是导致心磷脂缺乏和线粒体功能障碍的原因。到目前为止，还没有对心脏表型的系统评估。最近未发表的报告表明，心律失常的发生率增加，特别是在青少年和年轻人中。这项建议是一项对Barth综合征患者队列的观察性研究，旨在评估与年龄相关的心律失常风险，并调查心功能、骨骼肌病和生化与疾病严重程度的关系。该假说是存在与年龄相关的心律紊乱风险，且与心肌病的严重程度无关。其次，心功能不全的程度可能与其他变量有关，包括中性粒细胞减少、肉碱分布和骨骼肌病的程度。这一提议试图通过两个具体目标来证实这一假设。第一个目标将解决心律异常的分析，第二个目标将使用详细的超声心动图分析来研究心肌病，并将心脏表现与骨骼肌病以及包括白细胞计数、肉碱水平和胆固醇在内的生化和血液学变量进行比较。我们预计，这项研究的结果将对指导Barth综合征患者的医疗护理有价值，包括筛查心律失常，以及可能需要对心律失常进行药物或设备治疗。

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 Recent unpublished reports suggest an increased incidence of arrhythmia, especially among adolescents and young adults.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.