Abstract：
Long-chain 3-hydroxyacyl-CoA deficiency (LCHADD) and mitochondrial trifunctional protein (MTPD) belong to a group of inherited metabolic diseases affecting the degradation of long-chain chain fatty acids. During metabolic decompensation the incomplete degradation of fatty acids results in life-threatening episodes, coma and death. Despite fast identification at neonatal screening, LCHADD/MTPD present with progressive neurodegenerative symptoms originally attributed to the accumulation of toxic hydroxyl acylcarnitines and energy deficiency. Recently, it has been shown that LCHADD human fibroblasts display a disease-specific alteration of complex lipids. Accumulating fatty acids, due to defective β-oxidation, contribute to a remodeling of several lipid classes including mitochondrial cardiolipins and sphingolipids. In the last years the face of LCHADD/MTPD has changed. The reported dysregulation of complex lipids other than the simple acylcarnitines represents a novel aspect of disease development. Indeed, aberrant lipid profiles have already been associated with other neurodegenerative diseases such as Parkinson\'s Disease, Alzheimer\'s Disease, amyotrophic lateral sclerosis and retinopathy. Today, the physiopathology that underlies the development of the progressive neuropathic symptoms in LCHADD/MTPD is not fully understood. Here, we hypothesize an alternative disease-causing mechanism that contemplates the interaction of several factors that acting in concert contribute to the heterogeneous clinical phenotype.
摘要：
长链3-羟酰基辅酶A缺乏症(LCHADD)和线粒体三功能蛋白(MTPD)属于影响长链脂肪酸降解的一组遗传代谢性疾病。在代谢失代偿期间，脂肪酸的不完全降解导致危及生命的发作。昏迷和死亡。尽管在新生儿筛查中快速识别，LCHADD/MTPD出现进行性神经退行性症状，最初归因于有毒的羟基酰基肉碱和能量缺乏的积累。最近,研究表明,LCHADD人成纤维细胞表现出复杂脂质的疾病特异性改变.积累脂肪酸，由于β氧化缺陷，有助于重塑几种脂质类别，包括线粒体心磷脂和鞘脂。在过去几年中，LCHADD/MTPD的面貌发生了变化。所报道的复杂脂质而不是简单的酰基肉碱的失调代表了疾病发展的新方面。的确,异常的血脂谱已经与其他神经退行性疾病，如帕金森病，阿尔茨海默病,肌萎缩侧索硬化症和视网膜病变。今天,LCHADD/MTPD中进行性神经性症状发展的基础病理生理学尚未完全了解.这里,我们假设了一种替代的致病机制,该机制考虑了多种因素的相互作用,这些因素共同作用导致了异质性临床表型.
