Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Muscle Nerve. 2013 Jul;48(1):140-4. doi: 10.1002/mus.23766. Epub 2013 Jun 4.
CMT2A2 is associated with mutations in the mitofusin 2 gene, which encodes a protein involved in mitochondrial fusion. Ethambutol is an antimycobacterial agent associated with toxic optic neuropathies. Ethambutol-induced optic neuropathy occurs in patients with mutations in a related fusion gene, OPA1, which is responsible for autosomal dominant optic atrophy.
We describe a patient with CMT2A2 (MFN2 mutation: T669G, F223L) who developed accelerated weakness, vocal cord paralysis, and optic atrophy after receiving ethambutol.
Deterioration began within months of initiating ethambutol therapy. After discontinuation of ethambutol, neurologic deterioration stabilized with subsequent improvement in visual fields.
CMT2A2 is part of a group of genetic disorders which share an association with the process of mitochondrial fusion. This case shows that patients with CMT2A2, and possibly other mitochondrial fusion defects, may be uniquely susceptible to ethambutol-induced neurotoxicity. This has implications regarding the underlying pathophysiology of mitochondrial fusion defects.
CMT2A2 与线粒体融合蛋白 2 基因（MFN2）的突变相关，该基因编码一种参与线粒体融合的蛋白。乙胺丁醇是一种抗分枝杆菌药物，与毒性视神经病变有关。乙胺丁醇诱导的视神经病变发生在与相关融合基因 OPA1 突变的患者中，OPA1 负责常染色体显性视神经萎缩。
我们描述了一位 CMT2A2 患者（MFN2 突变：T669G、F223L），在接受乙胺丁醇治疗后出现进行性肌无力、声带麻痹和视神经萎缩。
在开始乙胺丁醇治疗后的数月内病情恶化。停用乙胺丁醇后，神经功能恶化稳定，随后视野改善。
CMT2A2 是一组遗传疾病的一部分，这些疾病与线粒体融合过程有关。本病例表明，CMT2A2 患者（可能还有其他线粒体融合缺陷）可能对乙胺丁醇诱导的神经毒性特别敏感。这对线粒体融合缺陷的潜在病理生理学有影响。
