2016 Scientific and Medical Conference about Barth Syndrome

会议摘要/摘要 巴特综合征(BTHS；OMIM#302060)是一种罕见的、威胁生命的、X连锁的多系统遗传病 主要影响男性[1-5]。它是一种独特的线粒体疾病。的基本特征。 证候有扩张型心肌病(有时为肥厚型心肌病)，肌肉发育不良，极端 疲劳/虚弱、中性粒细胞减少、生长延迟以及四氢杨酸油酰心磷脂(一种主要的磷脂)减少 线粒体内膜)。严重的并发症通常包括周期性口腔溃疡、慢性 腹泻，以及伴随而来的营养问题的喂养问题。尽管BTHS患者的存活率 随着更广泛的认识和更早的诊断，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，有定期报告的个人死亡，有时是“轻微的”或明显较轻- 禁用BTHS的表现。这些悲惨的事件强调了更好地理解这一点的必要性 并将这一知识与更好的临床治疗联系起来。即使BTHS增加了 在提高认识和改善儿科护理方面，仍然有许多BTHS个人没有得到知情的故事 医疗或适当的保险覆盖范围。 1983年，Peter Barth博士发表了对Barth综合征的第一个描述[1]，描述了所有主要的 临床表现，建立X连锁遗传模式，并描述线粒体的异常 肌肉和白细胞的结构和功能。此后，对BTHS的理解进展缓慢，直到 1996年，在后来被命名为他法津或TAZ的基因中发现了致病突变，这是 位于基因丰富的Xq28染色体区域[6]。对BTHS的另一次理解飞跃发生在2000年 Peter Vreken博士和他的同事发现，患者的成纤维细胞培养基本上 线粒体四氢杨酸油酰心磷脂水平缺失[7]。幸运的是，这一发现也与 将巴特综合征基金会(BSF)合并为一个非营利性的患者权益倡导组织。 自成立以来，BSF主办了两年一次的国际科学、医学和家庭会议 (以下简称会议)突出科学和临床进步，教育患者和他们的 家庭，以帮助处理患者的关切，促进BTHS研究和研究人员的进步， 并建立一个充满活力的以病人为中心的社区。这些独特的会议从简单的 几个儿子患有这种罕见疾病的家庭和他们的主治医生聚集在一起， 参加国际会议，在这些会议上，重要的科学和临床进展和新的 对实地调查人员进行招募、鼓励和支持。与大多数主要的国际 BTHS和BTHS相关生物化学的学生出席了这些会议，培养了高水平的， 激动人心的、富有成效的讨论，塑造了BTHS研究和临床进步的方向。 此外，科学与医学相结合的会议形式也 有助于提高其生产率。事实上，参加过以前的会议的大多数基础科学家 评论他们如何通过讨论他们的工作笔记在分子和细胞水平上获得新的见解 不仅与其他科学家和消息灵通的临床医生，而且还与BTHS个人及其家人。同样， 参加这些会议的医生们更好地了解了 他法津缺乏，这通知了他们的BTHS患者的护理结束很长一段时间。 重要的是，BSF还发起了一项年度研究资助计划(现已进入第13个年头)，该计划在 吸引了许多世界领先的心磷脂研究人员、心肌病专家和代谢专家 科学家将重点放在BTHS上。随后，关于BTHS或BTHS的科学/医学出版物数量 他法津基因每年都在增加；现在有超过117篇文章承认了BSF、其附属公司、其生物- 存储库，或BSF社区。得出这样的结论并不是不合理的，即BSF帮助促进了这些 出版和研究进展通过其两年一次的会议、其研究资助方案和 提供研究工具，如BTHS的鼠标模型和生物信息库。对治疗方法的探索 治疗或化合物一直是这些会议的主要焦点，尽管直到最近才开始临床 治疗方法已经能够被详细讨论。2014年会上的几个治疗理念 都被提出，并最终得到了BSF研究资助计划的支持。2016年，我们 期待听到这些治疗想法的进展，以及其他几个想法 自上次会议以来发展起来的。在2016年大会上，我们预计将讨论和评估8个以上 治疗的想法并排出现，当人们回忆起只有姑息治疗可用时，这是非同寻常的 当BSF刚开始的时候。这些由英国科学基金会赞助的两年一度的会议是为数不多的论坛之一， 可以有效地提出、讨论、批判性评估和采取行动。这些 会议为科学和医学增加了真正的价值，并为BTHS个人提供了真正的希望。

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.