Abrahão Agessandro, Pedroso José Luiz, Braga-Neto Pedro, Bor-Seng-Shu Edson, de Carvalho Aguiar Patricia, Barsottini Orlando Graziani Povoas
Division of General Neurology and Ataxia Unit, Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, Rua Pedro de Toledo 650 Vila Clementino, São Paulo, 04039-002, SP, Brazil,
Neurogenetics. 2015 Jul;16(3):151-60. doi: 10.1007/s10048-015-0439-z. Epub 2015 Feb 8.
Friedreich ataxia (FRDA) is the most common autosomal recessive ataxia worldwide. This review highlights the main clinical features, pathophysiological mechanisms, and therapeutic approaches for FRDA patients. The disease is characterized by a combination of neurological involvement (ataxia and neuropathy), cardiomyopathy, skeletal abnormalities, and glucose metabolism disturbances. FRDA is caused by expanded guanine-adenine-adenine (GAA) triplet repeats in the first intron of the frataxin gene (FXN), resulting in reduction of messenger RNA and protein levels of frataxin in different tissues. The molecular and metabolic disturbances, including iron accumulation, lead to pathological changes characterized by spinal cord and dorsal root ganglia atrophy, dentate nucleus atrophy without global cerebellar volume reduction, and hypertrophic cardiomyopathy. DNA analysis is the hallmark for the diagnosis of FRDA. There is no specific treatment to stop the disease progression in FRDA patients. However, a number of drugs are under investigation. Therapeutic approaches intend to improve mitochondrial functioning and to increase FXN expression.
弗里德赖希共济失调（FRDA）是全球最常见的常染色体隐性共济失调疾病。本综述重点介绍了FRDA患者的主要临床特征、病理生理机制及治疗方法。该疾病的特点是神经系统受累（共济失调和神经病变）、心肌病、骨骼异常以及葡萄糖代谢紊乱共同存在。FRDA是由铁转运蛋白基因（FXN）第一内含子中的鸟嘌呤-腺嘌呤-腺嘌呤（GAA）三联体重复序列扩增所致，导致不同组织中铁转运蛋白信使核糖核酸和蛋白质水平降低。包括铁蓄积在内的分子和代谢紊乱会引发以脊髓和背根神经节萎缩、齿状核萎缩（而小脑总体积无减小）以及肥厚型心肌病为特征的病理变化。DNA分析是诊断FRDA的标志。目前尚无能够阻止FRDA患者疾病进展的特效治疗方法。不过，有多种药物正在研究中。治疗方法旨在改善线粒体功能并增加FXN表达。
