Fujisawa Miwako, Sano Yasuteru, Omoto Masatoshi, Ogasawara Jyun-Ichi, Koga Michiaki, Takashima Hiroshi, Kanda Takashi
Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medical Science.
Department of Neurology, Yamaguchi Prefectural Grand Medical Center.
Rinsho Shinkeigaku. 2017 Sep 30;57(9):515-520. doi: 10.5692/clinicalneurol.cn-001036. Epub 2017 Aug 31.
We report a 59-year-old Japanese male who developed gradually worsening weakness and numbness of distal four extremities since age 50. His parents were first cousins, and blood and cerebral spinal examinations were unremarkable. Homozygous mutation of MME gene was detected and thus he was diagnosed as autosomal-recessive Charcot-Marie-Tooth disease 2T (AR-CMT2T); however, electrophysiological examinations revealed scattered demyelinative changes including elongated terminal latency in several peripheral nerve trunks. Sural nerve biopsy showed endoneurial edema and a lot of thinly myelinated nerve fibers with uneven distribution of remnant myelinated fibers within and between fascicles. Immunoglobulin treatment was initiated considering the possibility of superimposed inflammation and demyelination, and immediate clinical as well as electrophysiological improvements were noted. Our findings indicate that AR-CMT2T caused by MME mutation predisposes to a superimposed inflammatory demyelinating neuropathy. This is the first report which documented the co-existence of CMT2 and chronic inflammatory demyelinating polyneuropathy (CIDP); however, in the peripheral nervous system, neprilysin, a product of MME gene, is more abundant in myelin sheath than in axonal component. The fragility of myelin sheath due to mutated neprilysin may trigger the detrimental immune response against peripheral myelin in this patient.
我们报告一名59岁的日本男性，自50岁起四肢远端逐渐出现无力和麻木症状加重。他的父母是近亲，血液和脑脊液检查无异常。检测到MME基因纯合突变，因此他被诊断为常染色体隐性遗传性腓骨肌萎缩症2T型（AR-CMT2T）；然而，电生理检查显示在几条周围神经干中存在散在的脱髓鞘改变，包括终末潜伏期延长。腓肠神经活检显示神经内膜水肿，许多薄髓鞘神经纤维，束内和束间残余髓鞘纤维分布不均。考虑到可能存在叠加的炎症和脱髓鞘，开始进行免疫球蛋白治疗，并注意到临床和电生理立即得到改善。我们的研究结果表明，由MME突变引起的AR-CMT2T易发生叠加性炎性脱髓鞘性神经病。这是第一份记录CMT2与慢性炎性脱髓鞘性多发性神经病（CIDP）并存的报告；然而，在周围神经系统中，MME基因的产物中性肽链内切酶在髓鞘中的含量比轴突成分中更丰富。突变的中性肽链内切酶导致的髓鞘脆弱性可能引发该患者针对周围髓鞘的有害免疫反应。
