2016 Scientific and Medical Conference about Barth Syndrome

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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.