CARDIAC AND SKELETAL MUSCLE IN BARTH SYNDROME

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 Barth综合征是一种X连锁疾病，其特征为扩张型心肌病、周期性中性粒细胞减少症、骨骼肌病和生长缺陷。临床疾病表现是可变的，即使在家庭内。TAZ基因Xq 28处的突变是导致心磷脂缺乏和线粒体功能障碍的原因。迄今为止，尚未对心脏表型进行系统评价。最近未发表的报告表明心律失常的发病率增加，特别是在青少年和年轻人中。本提案是一项针对Barth综合征患者队列的观察性研究，旨在评价心律失常的年龄相关风险，以及研究心脏功能、骨骼肌病变和疾病严重程度的生化相关性之间的关系。该假设是，存在与年龄相关的心律失常风险，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，肉毒碱谱，骨骼肌病变的程度。 这一建议试图通过两个具体目标来证实这一假设。第一个目的是分析心律异常，第二个目的是使用详细的超声心动图分析研究心肌病，并将心脏性能与骨骼肌病以及生化和血液学变量（包括白色血细胞计数、肉毒碱水平和胆固醇）进行比较。 我们预计，本研究的结果将在指导Barth综合征患者的医疗护理方面具有价值，包括心律失常筛查和心律失常药物或器械治疗的潜在需求。

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 Recent unpublished reports suggest an increased incidence of arrhythmia, especially among adolescents and young adults.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