Nishikura Noriko, Yamagata Takanori, Morimune Takao, Matsui Jun, Sokoda Tatsuyuki, Sawai Chihiro, Sakaue Yuko, Higuchi Yujiro, Hashiguchi Akihiro, Takashima Hiroshi, Takeuchi Yoshihiro, Maruo Yoshihiro
Department of Pediatrics, Shiga University of Medical Science, Otsu 520-2192, Japan.
Department of Pediatrics, Jichi Medical University, Shimotsuke, Tochigi, Japan.
Brain Dev. 2019 Feb;41(2):201-204. doi: 10.1016/j.braindev.2018.08.006. Epub 2018 Aug 31.
X-linked Charcot-Marie-Tooth disease type 5 (CMTX5) is an X-linked disorder characterized by early-onset sensorineural hearing impairment, peripheral neuropathy, and progressive optic atrophy. It is caused by a loss-of-function mutation in the phosphoribosyl pyrophosphate synthetase 1 gene (PRPS1), which encodes isoform I of phosphoribosyl pyrophosphate synthetase (PRS-I). A decreased activity leads to nonsyndromic sensorineural deafness (DFN2), CMTX5, and Arts syndrome depending upon residual PRS-I activity. Clinical and neurophysiological features of pediatric CMTX5 are poorly defined. We report two male siblings with peripheral neuropathy and prelingual sensorineural hearing loss who carried a novel c.319A>G (p.Ile107Val) PRPS1 missense mutation. They exhibited recurrent episodes of transient proximal muscle weakness, showing Gowers' sign and waddling gait after suffering from febrile illness. This transient weakness has not been previously reported in CMTX5. A patient with Arts syndrome was reported to have transient proximal weakness after febrile illness. The transient weakness presenting in both CMTX5 and Arts syndrome suggests an overlap of signs and a continuous spectrum of PRS-I hypoactivity disease. Children presenting with transient neurological signs should be evaluated for peripheral neuropathy and consider genetic analysis for PRPS1.
X连锁5型夏科-马里-图斯病（CMTX5）是一种X连锁疾病，其特征为早发性感觉神经性听力障碍、周围神经病变和进行性视神经萎缩。它由磷酸核糖焦磷酸合成酶1基因（PRPS1）的功能丧失性突变引起，该基因编码磷酸核糖焦磷酸合成酶同工型I（PRS-I）。活性降低会导致非综合征性感觉神经性耳聋（DFN2）、CMTX5和阿茨综合征，具体取决于PRS-I的残余活性。儿童CMTX5的临床和神经生理学特征尚不明确。我们报告了两名患有周围神经病变和语前感觉神经性听力损失的男性同胞，他们携带一种新的c.319A>G（p.Ile107Val）PRPS1错义突变。他们在发热性疾病后出现反复的短暂近端肌无力发作，表现为Gowers征和鸭步。这种短暂性肌无力此前在CMTX5中未见报道。有一名阿茨综合征患者被报道在发热性疾病后出现短暂近端肌无力。CMTX5和阿茨综合征中均出现的短暂性肌无力提示体征重叠以及PRS-I活性低下疾病的连续谱。出现短暂性神经体征的儿童应评估是否患有周围神经病变，并考虑对PRPS1进行基因分析。
