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.

会议概要/摘要 巴特综合征（BTHS；OMIM #302060）是一种罕见、危及生命的 X 连锁多系统遗传性疾病 主要影响男性[1-5]。 综合征包括扩张型心肌病（有时为肥厚型心肌病）、肌肉发育不全、极度 疲劳/虚弱、中性粒细胞减少、生长延迟和四亚油酰心磷脂（一种主要磷脂）减少 严重的并发症通常包括周期性口腔溃疡、慢性口腔溃疡。 尽管 BTHS 个体的生存率有所下降，但腹泻、喂养问题以及随之而来的营养问题仍然存在。 随着更广泛的认识和早期诊断的改善，受影响的男孩和男子仍然面临潜在的风险 致命的并发症，包括心力衰竭、室性心律失常和压倒性的细菌感染。 不幸的是，定期有报告称，有时患有“轻度”或明显较轻的疾病的人死亡。 这些悲惨事件强调了更好地理解这一点的必要性。 并将这些知识与更好的临床治疗联系起来，即使 BTHS 有所增加。 意识和改进的儿科护理，仍然有许多 BTHS 个人没有获得知情的故事 医疗护理或适当的保险范围。 1983 年，Peter Barth 博士首次发表了对 Barth 综合征的描述 [1]，描述了所有主要症状 临床发现，建立了 X 连锁遗传模式，并描述了线粒体的异常 此后，对肌肉和白细胞的结构和功能的理解进展缓慢，直到 1996 年，在随后被命名为 tafazzin 或 TAZ 的基因中发现了致病突变，该基因是 位于基因丰富的 Xq28 染色体区域 [6]，理解 BTHS 的另一个飞跃出现在 2000 年。 Peter Vreken 博士及其同事发现，来自患者的成纤维细胞培养物基本上具有 线粒体四亚油酰心磷脂水平缺失 [7] 幸运的是，这一发现也与 巴斯综合症基金会 (BSF) 成立为非营利性患者权益团体。 自成立以来，BSF 赞助了两年一度的国际科学、医学和家庭会议 （以下简称会议）旨在突出科学和临床进展，教育患者及其患者 家庭，帮助处理患者的担忧，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会议演变而来的。 几个儿子患有这种罕见疾病的家庭和他们的治疗医生聚集在一起， 参加国际会议，展示重要的科学和临床进展以及新的进展 大多数主要国际组织都招募、鼓励和支持该领域的研究人员。 BTHS 和 BTHS 相关生物化学的学生出席，这些会议培养了高水平、 刺激且富有成效的讨论塑造了 BTHS 研究和临床进展的方向。 此外，将科学与医学演讲相结合的会议形式也 事实上，参加过往届会议的大多数基础科学家都对其生产力做出了贡献。 评论了他们如何通过讨论他们的工作而不是在分子和细胞水平上获得新的见解 不仅与其他科学家和知情的赞助人，而且还与 BTHS 个人及其家人。 参加这些会议的医生可以更好地了解 tafazzin 缺乏症，在治疗结束后很长一段时间才通知 BTHS 患者的护理。 重要的是，BSF 还启动了年度研究资助计划（现已进入第 13 个年头），该计划成功地 吸引了众多世界领先的心磷脂研究人员、心肌病专家和代谢专家 随后，有关 BTHS 或 BTHS 的科学/医学出版物的数量。 tafazzin 基因逐年增加；现在有超过 117 篇文章承认 BSF、其附属机构、其生物技术的支持 存储库或 BSF 社区 可以得出 BSF 帮助促进这些的结论并非没有道理。 通过其两年一次的会议、研究资助计划以及 提供研究工具，例如 BTHS 小鼠模型和生物库 寻找治疗方法。 治疗或化合物始终是这些会议的主要焦点，尽管直到最近才出现临床 在 2014 年的会议上，我们对一些治疗想法进行了详细讨论。 被提议并最终通过 2016 年 BSF 研究资助计划得到支持。 期待听到这些治疗理念的进展以及其他一些已经被证实的想法 自上次会议以来我们预计将讨论和评估超过八项。 并排的治疗理念，当人们回想起当时只有姑息治疗时，这是非同寻常的 这些由 BSF 主办的两年一度的会议是为数不多的“长凳”论坛之一。 可以有效地呈现、讨论、批判性评估并采取行动。 会议为科学和医学增添了真正的价值，并为 BTHS 个人带来了真正的希望。