PEX10基因突变导致Zellweger谱系疾病一家系研究并文献复习  

A family study of Zellweger spectrum disorders due to mutations in the PEX10 gene and literature review

作　　者：崔新宇 代莉 张同霞[1] 单晶莉[1] 徐广润[1] 赵玉英[1] Cui Xinyu;Dai Li;Zhang Tongxia;Shan Jingli;Xu Guangrun;Zhao Yuying(Department of Neurology,Qilu Hospital of Shandong University,Jinan 250012,China;Department of Neurology,Anqiu City Hospital of Shandong Province,Anqiu 262100,China)

机构地区：[1]山东大学齐鲁医院神经内科,济南250012 [2]山东省安丘市市立医院,安丘262100

出　　处：《中华神经科杂志》2023年第10期1150-1157,共8页Chinese Journal of Neurology

摘　　要：目的报道PEX10基因突变所致Zellweger谱系疾病一家系,提高临床医师对该疾病的认识水平。方法收集2022年7月山东大学齐鲁医院神经内科收治的确诊为PEX10基因突变所致Zellweger谱系疾病一姐弟共患病家系的临床及遗传学资料,并进行文献复习。结果该家系先证者为24岁女性,因“行走不稳8年,加重伴蹲起费力1年”就诊,头颅磁共振成像(MRI)显示小脑萎缩,肌电图提示运动、感觉均受累的周围神经病,纯音听阈测定示神经性耳聋。先证者弟弟15岁,表现为“行走不稳及蹲起费力2年”,头颅MRI及肌电图与先证者类似,二者均伴有肝功能异常。先证者全外显子测序结果提示PEX10基因复合杂合变异,突变位点为c.992G>A(p.R331Q)和c.988T>C(p.C330R),均为疑似致病性变异,且分别来自父母。先证者弟弟亦携带上述两处变异。从国内外主要数据库共检索到PEX10基因突变导致Zellweger谱系疾病病例报道英文文献9篇(其中1篇为国内学者发表),累计15例患者,大多数患者为儿童及青少年期起病,首发症状多为共济失调且进展缓慢,绝大多数患者颅脑MRI显示小脑萎缩,多数进行肌电图检查的患者发现周围神经病变。对姐弟二人给予限制植酸饮食及服用精氨酸和熊脱氧胆酸,3个月后行走不稳症状及肝功能均有所好转。结论对于不明原因的共济失调,如合并周围神经病及肝功能异常,应当考虑Zellweger谱系疾病的可能。限制植酸饮食,同时口服左旋精氨酸及熊脱氧胆酸可能会使患者获益。Objective To report a family of Zellweger spectrum disorders(ZSD)caused by mutations in the PEX10 gene and to increase the level of awareness of the disease among clinicians.Methods The clinical and genetic data of a brother-sister co-morbidity family with ZSD due to PEX10 gene mutation admitted to the Department of Neurology,Qilu Hospital of Shandong University in July 2022 were collected and a literature review was performed.Results The proband was a 24-year-old female who was admitted to the Qilu Hospital of Shandong University due to unstable walking for 8 years and aggravated for 1 year with squatting effort.Cranial magnetic resonance imaging(MRI)showed cerebellar atrophy,electromyography suggested peripheral neuropathy with motor and sensory involvement,and pure tone hearing threshold measurement showed neurogenic deafness.The 15-year-old brother of the proband presented with"unsteadiness in walking and difficulty in squatting for 2 years".His cranial MRI and electromyography were similar to those of the proband,and his laboratory results suggested abnormal liver function.The whole exon sequencing results of the proband suggested a compound heterozygous mutation in the PEX10 gene with c.992G>A(p.R331Q)and c.988T>C(p.C330R)mutations and both were likely pathogenic mutations and respectively from her parents.And her brother also carried the above variants.A total of 9 case reports in English literature(1 of which was published by domestic scholars)were retrieved from major domestic and international databases on PEX10 gene mutations causing ZSD,with a total of 15 patients,most of whom had childhood and adolescent onset.The most common initial symptom was slowly progressed ataxia.The majority of patients showed cerebellar atrophy on cranial MRI and peripheral neuropathy was found in the most patients.The 2 patients were suggested to have phytic acid-free food,at the same time,they bagan taking L-arginine and ursodeoxycholic acid.Fortunately,both the ataxia symptom and liver function of them were dramatically a

关 键 词：过氧化物酶体类 Zellweger谱系疾病 共济失调 周围神经病 

分 类 号：R596[医药卫生—内科学]