Research Service, Veterans Affairs Medical Center, Albany, New York 12208, USA.
J Neuropathol Exp Neurol. 2013 Feb;72(2):78-90. doi: 10.1097/NEN.0b013e31827e5762.
Friedreich ataxia is an autosomal recessive disorder that affects children and young adults. The mutation consists of a homozygous guanine-adenine-adenine trinucleotide repeat expansion that causes deficiency of frataxin, a small nuclear genome-encoded mitochondrial protein. Low frataxin levels lead to insufficient biosynthesis of iron-sulfur clusters that are required for mitochondrial electron transport and assembly of functional aconitase, and iron dysmetabolism of the entire cell. This review of the neuropathology of Friedreich ataxia stresses the critical role of hypoplasia and superimposed atrophy of dorsal root ganglia. Progressive destruction of dorsal root ganglia accounts for thinning of dorsal roots, degeneration of dorsal columns, transsynaptic atrophy of nerve cells in Clarke column and dorsal spinocerebellar fibers, atrophy of gracile and cuneate nuclei, and neuropathy of sensory nerves. The lesion of the dentate nucleus consists of progressive and selective atrophy of large glutamatergic neurons and grumose degeneration of corticonuclear synaptic terminals that contain γ-aminobutyric acid (GABA). Small GABA-ergic neurons and their projection fibers in the dentato-olivary tract survive. Atrophy of Betz cells and corticospinal tracts constitute a second intrinsic CNS lesion. In light of the selective vulnerability of organs and tissues to systemic frataxin deficiency, many questions about the pathogenesis of Friedreich ataxia remain.
弗里德赖希共济失调是一种常染色体隐性疾病，影响儿童和青年。该突变由鸟嘌呤-腺嘌呤-腺嘌呤三核苷酸重复扩展引起，导致铁蛋白缺乏，铁蛋白是一种小核基因组编码的线粒体蛋白。铁蛋白水平低导致铁硫簇的生物合成不足，而铁硫簇是线粒体电子传递和功能性 aconitase 的组装所必需的，整个细胞的铁代谢也会失调。本文综述了弗里德赖希共济失调的神经病理学，强调了背根神经节发育不良和叠加萎缩的关键作用。背根神经节的进行性破坏导致背根变薄、背柱变性、克拉克柱和背侧脊髓纤维中的神经细胞突触萎缩、薄束和楔束核萎缩以及感觉神经病变。齿状核的病变包括谷氨酸能大神经元的进行性和选择性萎缩以及含有γ-氨基丁酸 (GABA) 的皮质核突触末梢的颗粒状变性。齿状橄榄束中的小 GABA 能神经元及其投射纤维存活。Betz 细胞和皮质脊髓束的萎缩构成了中枢神经系统的第二个内在病变。鉴于器官和组织对系统性铁蛋白缺乏的选择性易感性，弗里德赖希共济失调的发病机制仍存在许多问题。
