Department of Pharmacology & Therapeutics, Biochemistry & Medical Genetics, University of Manitoba, Winnipeg, MB, Canada.
DREAM, Children's Hospital Research Institute of Manitoba, Winnipeg, MB, Canada.
Mol Cell Biochem. 2021 Mar;476(3):1605-1629. doi: 10.1007/s11010-020-04021-0. Epub 2021 Jan 7.
Barth syndrome is a rare X-linked genetic disease classically characterized by cardiomyopathy, skeletal myopathy, growth retardation, neutropenia, and 3-methylglutaconic aciduria. It is caused by mutations in the tafazzin gene localized to chromosome Xq28.12. Mutations in tafazzin may result in alterations in the level and molecular composition of the mitochondrial phospholipid cardiolipin and result in large elevations in the lysophospholipid monolysocardiolipin. The increased monolysocardiolipin:cardiolipin ratio in blood is diagnostic for the disease, and it leads to disruption in mitochondrial bioenergetics. In this review, we discuss cardiolipin structure, synthesis, and function and provide an overview of the clinical and cellular pathophysiology of Barth Syndrome. We highlight known pharmacological management for treatment of the major pathological features associated with the disease. In addition, we discuss non-pharmacological management. Finally, we highlight the most recent promising therapeutic options for this rare mitochondrial disease including lipid replacement therapy, peroxisome proliferator-activated receptor agonists, tafazzin gene replacement therapy, induced pluripotent stem cells, mitochondria-targeted antioxidants and peptides, and the polyphenolic compound resveratrol.
巴德-希利综合征是一种罕见的 X 连锁遗传性疾病，其特征为心肌病、骨骼肌病、生长迟缓、中性粒细胞减少症和 3-甲基戊烯二酸尿症。它是由位于 Xq28.12 染色体上的 tafazzin 基因突变引起的。tafazzin 基因突变可能导致线粒体磷脂心磷脂的水平和分子组成发生改变，并导致溶血磷脂单心磷脂酰甘油的含量大幅升高。血液中单心磷脂酰甘油：心磷脂的比值升高是该疾病的诊断依据，它导致线粒体生物能量学的破坏。在这篇综述中，我们讨论了心磷脂的结构、合成和功能，并概述了巴德-希利综合征的临床和细胞病理生理学。我们重点介绍了已知的药理学治疗方法，用于治疗与该疾病相关的主要病理特征。此外，我们还讨论了非药物治疗方法。最后，我们重点介绍了针对这种罕见的线粒体疾病的最新有前途的治疗选择，包括脂质替代疗法、过氧化物酶体增殖物激活受体激动剂、tafazzin 基因替代疗法、诱导多能干细胞、线粒体靶向抗氧化剂和肽以及多酚化合物白藜芦醇。
