摘要目的 报道2例常染色体隐性遗传性腓骨肌萎缩症2K型(autosomal recessive Charcot-Marie-Tooth disease 2K, AR-CMT2K)患者的临床和病理改变特点.方法 例1为9岁女童,抬脚费力6年,小腿肌萎缩、跟腱挛缩3年.例2为8岁男童,出现抬脚费力、跟腱挛缩、小腿肌萎缩3年,伴随近端无力2年.例1正中神经运动神经传导速度为48.1 m/s,复合肌肉动作电位(CMAP)波幅下降46%;例2正中神经运动神经传导速度为47.6 m/s,CMAP下降69%.对2例患儿进行腓肠神经活体组织检查和靶向基因二代测序检查.结果 2例患儿腓肠神经的有髓神经纤维密度分别为8 407个/mm2和7 714个/mm2,直径大于8 μm的有髓神经纤维比例分别为2.6%和0.2例患儿均可见小有髓神经纤维再生簇结构,例1可见薄髓鞘有髓神经纤维,例2可见有髓神经纤维髓鞘局部折叠以及不典型洋葱球样结构,电镜下可见轴索内线粒体聚集.2例患儿均存在神经节苷脂诱导分化相关蛋白1基因的致病性突变,其中例1为c.466G>A(p.A156T)和c.767A>G(p.H256R)复合杂合突变,例2为c.767A>G和c.845G>A(p.R282H)复合杂合突变.结论 AR-CMT2K可以在儿童早期伴发跟腱挛缩,腓肠神经的病理改变以大直径有髓神经纤维丢失为主,伴轴索内线粒体分布异常以及髓鞘损害.

abstractsObjective To report the clinical and peripheral neuropathological findings in two patients with autosomal recessive Charcot-Marie-Tooth disease 2K(AR-CMT2K).Methods Case one was a nine year-old girl.She had distal weakness of lower limbs for six years, with calf atrophy and contracture of Achilles tendon for three years.Case two was an eight year-old boy.He had distal weakness of lower limbs with contracture of Achilles tendon and calf muscle atrophy for three years, and proximal weakness of low limbs for two years.The motor nerve conduction velocities in median nerves were 48.1 m/s in case one and 47.6 m/s in case two.The compound motor action potential amplitude of median nerves decreased by 46% in case one and 69% in case two.Sural nerve biopsies and gene targeted next-generation sequencing were performed in both patients.Results Density of myelinated fibers was 8 407/mm2 in case one and 7 714/mm2 in case two.The ratio of myelinated fibers with diameter over 8 μm was 2.6% in case one and 0 in case two.Both patients had small regenerating cluster of myelinated fibers.Thin myelinated fibers appeared in case one.In case two, atypical onion bulb formations with focal folded myelin appeared, and electromicroscopy revealed mitochondrial aggregate in axons.Compound heterozygous mutations of ganglioside-induced differentiation associated protein 1 gene were detected in both patients, including c.767A>G(p.H256R) and c.466G>A (p.A156T) in case one and c.767A>G and 845G>A(p.R282H) in case two.Conclusions Contracture of Achilles tendon may appear in early childhood of AR-CMT2K patients.The main pathological changes in sural nerve are loss of large myelinated fibers, mitochondrial aggregate in axons and myelin abnormalities.