2016 Scientific and Medical Conference about Barth Syndrome

2016年巴斯综合症科学与医学会议

• 批准号: 9191404
• 负责人: Matthew J Toth
• 金额: $ 2.5万
• 依托单位: BARTH SYNDROME FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9191404
• 关键词: 3-Methylglutaconic aciduria type 2; Address; Adoption; Affect; Ally; Awareness; Bacterial Infections; Bezafibrate; Biochemical Genetics; Biochemistry; Blood; Cardiolipins; Cardiomyopathies; Caring; Cessation of life; Characteristics; Childhood; Chronic; Clinic; Clinical; Clinical Research; Clinical Treatment; Clinical Trials; Collaborations; Communication; Communities; Data; Development; Diabetes Mellitus; Diarrhea; Dilated Cardiomyopathy; Disease; Early Diagnosis; Event; Exercise; Family; Fatigue; Fibroblasts; Fostering; Foundations; Genes; Goals; Growth; Health Personnel; Healthcare; Hearing; Heart; Heart failure; Hereditary Disease; Hypertrophic Cardiomyopathy; Individual; Industry; Inner mitochondrial membrane; Insurance Coverage; International; Intervention; Knowledge; Lead; Leukocytes; Life; Link; Lipids; Medical; Medicine; Messenger RNA; Metabolic; Mission; Mitochondria; Mitochondrial Diseases; Modality; Molecular; Morbidity - disease rate; Muscle; Mutation; Myopathy; National Heart, Lung, and Blood Institute; Neutropenia; Nutraceutical; Nutritional; Online Mendelian Inheritance In Man; Oral; Palliative Care; Patients; Phospholipids; Physicians; Physiological; Play; Population; Positioning Attribute; Productivity; Publications; Published Comment; Publishing; Rare Diseases; Recruitment Activity; Reporting; Request for Applications; Research; Research Personnel; Research Project Grants; Risk; Role; Science; Scientific Advances and Accomplishments; Scientist; Series; Shapes; Side; Son; Staging; Structure; Students; Symptoms; Syndrome; System; Therapeutic; Time; Translating; Ulcer; United Kingdom; United States; Update; Ventricular Arrhythmia; Vision; Work; abstracting; base; bench to bedside; boys; enzyme replacement therapy; feeding; improved; insight; interest; male; meetings; men; mortality; mouse model; novel therapeutics; patient advocacy group; patient oriented; pre-clinical; programs; repository; skeletal; symposium; therapy development; tool; web site

SUMMARY/ABSTRACT OF THE CONFERENCE Barth syndrome (BTHS; OMIM #302060) is a rare, life-threatening, X-linked, multi-system genetic disorder affecting primarily males [1-5]. It is a unique mitochondrial disease. The cardinal characteristics of the syndrome are dilated cardiomyopathy (sometimes hypertrophic cardiomyopathy), muscle hypoplasia, extreme fatigue/weakness, neutropenia, growth delay, and a reduction of tetralinoleoyl cardiolipin (a major phospholipid of the mitochondrial inner membrane). Serious complications often include cyclical oral ulceration, chronic diarrhea, and feeding problems with attendant nutritional concerns. Although survival for BTHS individuals has improved with wider recognition and earlier diagnosis, affected boys and men remain at risk for potentially lethal complications, including heart failure, ventricular arrhythmias, and overwhelming bacterial infections. Unfortunately, there are periodic reports of deaths of individuals sometimes with “mild” or apparently less- disabling manifestations of BTHS. These tragic events emphasize the need for a better understanding of this disease and for linking this knowledge towards better clinical treatments. Even with increased BTHS awareness and improved pediatric care, there are still many stories of BTHS individuals not receiving informed medical care or proper insurance coverage. In publishing the first description of Barth syndrome in 1983 [1], Dr. Peter Barth delineated all of the principal clinical findings, established the X-linked mode of inheritance, and described the abnormalities of mitochondrial structure and function in muscle and leukocytes. Progress in understanding BTHS thereafter was slow until 1996 when causative mutations were found in the gene subsequently designated tafazzin or TAZ, which is located in the gene-rich Xq28 chromosomal region [6]. Another leap in understanding BTHS came in 2000 with the discovery by Dr. Peter Vreken and colleagues that fibroblast cultures from patients have essentially absent levels of mitochondrial tetralinoleoyl cardiolipin [7]. Fortunately, this discovery also coincided with the incorporation of the Barth Syndrome Foundation (BSF) as a non-profit, patient-advocacy group. Since its inception BSF has sponsored biennial International Scientific, Medical and Family Conferences (hereafter referred to as Conferences) to highlight scientific and clinical advances, to educate patients and their families, to help deal with patient concerns, to promote the advancement of BTHS research and researchers, and to establish a vibrant patient-centered community. These unique Conferences have evolved from simple gatherings of a few families who have sons suffering from this rare disease along with their treating physicians, to International Conferences where important scientific and clinical advancements are presented and new investigators to the field are recruited, encouraged, and supported. With most of the principal international students of BTHS and BTHS-related biochemistry in attendance, these Conferences foster high-level, stimulating, and productive discussions that shape the direction of BTHS research and clinical progress. Furthermore, the format of the Conferences to combine the scientific with the medical presentations also contributes to its productivity. Indeed, most of the basic scientists who attended previous Conferences commented on how they gained new insights on a molecular and cellular level by discussing their work not only with other scientists and informed clinicians, but also with BTHS individuals and their families. Similarly, physicians attending these Conferences acquire a better understanding of the physiological consequences of tafazzin deficiency, which informed the care of their BTHS patients long after the sessions ended. Importantly, BSF also initiated an annual research grant program (now in its 13th year) which succeeded in attracting many of the world’s leading cardiolipin researchers, cardiomyopathy experts, and metabolic scientists to focus on BTHS. Subsequently, the number of scientific/medical publications about BTHS or the tafazzin gene increases yearly; over 117 articles now acknowledge the support of BSF, its affiliates, its bio- repository, or the BSF community. It is not unreasonable to conclude that BSF has helped to promote these publication and research advances through its biennial Conferences, its Research Grant Program, and by providing research tools such as the mouse model of BTHS and a bio-repository. The search for therapeutic treatments or compounds is always a main focus of these Conferences, though it is only recently that clinical therapies have been able to be discussed in any detail. At the 2014 Conference several therapeutic ideas were proposed and were eventually supported through the BSF Research Grant Program. For 2016 we expect to hear about the progress of these therapeutic ideas as well as several more ideas that have developed since the last Conference. At the 2016 Conference we expect to discuss and evaluate over eight therapeutic ideas, side-by-side, which is extraordinary when one recalls that only palliative care was available when BSF first started. These BSF-sponsored biennial Conferences are one of the few forums where “bench to bedside” possibilities can be effectively presented, discussed, critically evaluated, and acted upon. These Conferences add real value to science and medicine, and provide real hope to BTHS individuals.

会议的摘要/摘要 Barth综合征（BTHS; OMIM＃302060）是一种罕见的，威胁生命的，X连锁的多系统遗传疾病 影响原发性男性[1-5]。这是一种独特的线粒体疾病。的基本特征 综合征是扩张的心肌病（有时是肥厚的心肌病），肌肉发育不全，极端 疲劳/弱点，中额，生长延迟和次拉氨基烯酰苯胺脂蛋白的降低（主要磷脂 线粒体内膜）。严重的并发症通常包括周期性的口腔溃疡，慢性 腹泻，以及随之而来的营养问题喂养问题。虽然BTHS个人的生存 通过更广泛的识别和更早的诊断，受影响的男孩和男性仍处于潜在的风险中 致命并发症，包括心力衰竭，心室心律不齐和压倒性细菌感染。 不幸的是，有定期报道有时会有“轻度”或显然较少的人死亡 禁用BTH的表现。这些悲惨的事件强调需要更好地理解这一点 疾病并将这些知识与更好的临床治疗联系起来。即使增加了BTH 意识和改善的儿科护理，仍然有很多关于BTH的人未收到知情的故事 医疗或适当的保险范围。 彼得·巴特（Peter Barth）博士在出版1983年巴特综合症的第一个描述时，介绍了所有校长 临床发现，建立了X连锁的遗传模式，并描述了线粒体的异常 肌肉和白细胞的结构和功能。此后理解BTH的进展很慢，直到 1996年，在基因中发现了真实的突变，随后指定为tafazzin或taz， 位于富基因的XQ28染色体区域中[6]。理解BTH的另一个飞跃是在2000年 随着彼得·弗雷肯（Peter Vreken）和同事的发现，患者的成纤维细胞培养本质上是 缺乏线粒体四烯烯烃心氨基脂蛋白的水平[7]。幸运的是，这一发现也与 将Barth综合征基金会（BSF）纳入非营利性，患者顾问组。 自成立以来，BSF赞助了双年展的国际科学，医学和家庭会议 （以下称为会议）强调科学和临床进步，以教育患者及其 家庭，帮助应对患者的关注，以促进BTHS研究和研究人员的进步， 并建立一个充满活力的以患者为中心的社区。这些独特的会议是从简单的 少数有儿子患有这种罕见疾病的家庭的聚会以及他们的治疗医生， 举办重要的科学和临床进步并新的国际会议 招募，鼓励和支持该领域的调查人员。与大多数主要国际 BTH和与BTH相关的生物化学的学生出席了会议，培养了高级的会议， 刺激塑造BTHS研究和临床进步方向的产品讨论。 此外，还将科学与医学介绍相结合的会议格式 有助于其生产力。确实，参加以前会议的大多数基本科学家 评论了他们如何通过讨论他们的工作而获得分子和细胞水平上的新见解 仅与其他科学家和知情的临床医生一起，还与BTHS个人及其家人一起。相似地， 参加这些会议的医生可以更好地了解 Tafazzin缺乏症，后者在课程结束后很长一段时间为其BTHS患者的护理提供了信息。 重要的是，BSF还启动了一项年度研究赠款计划（现已进入第13年），该计划成功 吸引许多世界领先的心磷脂研究人员，心肌病专家和代谢 科学家专注于BTH。随后，有关BTH或的科学/医学出版物的数量 Tafazzin基因每年增加；现在，有117篇文章承认BSF的支持，其分支机构，其生物 - 存储库或BSF社区。包括BSF帮助推广这些并不是没有道理的 出版和研究通过其每两年一次的会议，研究赠款计划以及通过 提供研究工具，例如BTH的鼠标模型和生物依赖性。寻找治疗 治疗或化合物始终是这些会议的主要重点，尽管直到最近才临床 疗法已经可以详细讨论。在2014年会议上几个治疗想法 被提出，有时通过BSF研究赠款计划得到支持。 2016年我们 期望听到这些治疗想法的进步以及更多的想法 自上次会议以来开发。在2016年会议上，我们希望讨论和评估八个 治疗想法，并排，当人们回想起只有姑息治疗时，这是非凡的 当BSF刚开始时。这些BSF赞助的双年展会议是少数几个论坛之一。 可以有效地提出，讨论，进行批判性评估和采取行动。 会议为科学和医学增添了真正的价值，并为BTHS个人提供了真正的希望。