PDF(Pubmed)
Abstract：
TANGO2 deficiency disease (TDD) is a rare genetic disorder estimated to affect ∼8000 individuals worldwide. It causes neurodegeneration often accompanied by potentially lethal metabolic crises that are triggered by diet or illness. Recent work has demonstrated distinct lipid imbalances in multiple model systems either depleted for or devoid of the TANGO2 protein, including human cells, fruit flies and zebrafish. Importantly, vitamin B5 supplementation has been shown to rescue TANGO2 deficiency-associated defects in flies and human cells. The notion that vitamin B5 is needed for synthesis of the lipid precursor coenzyme A (CoA) corroborates the hypothesis that key aspects of TDD pathology may be caused by lipid imbalance. A natural history study of 73 individuals with TDD reported that either multivitamin or vitamin B complex supplementation prevented the metabolic crises, suggesting this as a potentially life-saving treatment. Although recently published work supports this notion, much remains unknown about TANGO2 function, the pathological mechanism of TDD and the possible downsides of sustained vitamin supplementation in children and young adults. In this Perspective, we discuss these recent findings and highlight areas for immediate scientific attention.
摘要：
TANGO2缺乏症（TDD）是一种罕见的遗传性疾病，估计会影响全球约8000人。它会导致神经变性，通常伴随着饮食或疾病引发的潜在致命的代谢危机。最近的工作已经证明了在多个模型系统中明显的脂质失衡，无论是耗尽还是缺乏TANGO2蛋白，包括人类细胞,果蝇和斑马鱼.重要的是,补充维生素B5已被证明可以挽救苍蝇和人体细胞中与TANGO2缺乏相关的缺陷。合成脂质前体辅酶A（CoA）需要维生素B5的观点证实了以下假设：TDD病理学的关键方面可能是由脂质失衡引起的。一项针对73名TDD患者的自然史研究报告说，补充多种维生素或复合维生素B可以预防代谢危机。表明这是一种潜在的挽救生命的治疗方法。尽管最近发表的作品支持这个概念，关于TANGO2功能还有很多未知，TDD的病理机制以及儿童和年轻人持续补充维生素的可能缺点。从这个角度来看,我们讨论了这些最新发现，并强调了需要立即科学关注的领域。
