[Progressive cavitating leukoencephalopathy: four cases and literatures review].

Objective: To analyze the clinical and genetic features of progressive cavitating leukoencephalopathy (PCL). Method: The data of clinical and genetic features of 4 PCL patients diagnosed by Beijing Children's Hospital between January 2015 and January 2016 were analyzed. The cases with complete clinical data retrieved on literature search at China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform and PubMed (up to August 2016) by using search terms of"NDUFV1" ,"NDUFS1" , or"leukoencephalopathy" , were summarized. Result: There were three females and one male, two of which were compatriots. The age of onset ranged from 6 months to 15 months. All four children's first symptoms were motor development regression, and the developmental milestones were almost normal before the onset. Of the 4 patients, 3 had cognitive impairment, 1 had seizures, 4 had dystonia and pyramidal impairment, 2 had emaciation, and 1 had nystagmus. The lactate concentrations of 4 patients were normal in blood. One patient had lactaciduria in the urinary organic acid analysis. Cranial magnetic resonance imaging (MRI) of all patients showed leukoencephalopathy, involved in the corpus callosum, and three patients accompanied by cystic lesions. Follow up for 2-13 years showed that the physical and language development were improved. Genetic analysis revealed that mutations in NDUFS1 were found in three patients and NDUFV1 mutation was found in one patient. All six mutations (p.Arg377Cys and p. Arg377His in NDUFV1; p. Arg482Glyfs(*)5, p.Thr368Pro, p.Tyr454X and p. Asp565Gly in NDUFS1) are novel. Five English case reports including 10 PCL patients were collected. Together with this group of 4 cases, a total of 14 cases were involved. All 14 children patients had motor development regression, 11 cases had cognitive impairment and dystonia, 6 cases had pyramidal impairment, 5 cases had irritability, 4 cases had epilepsy and nystagmus, 3 cases had strabismus and swallowing difficulty. Cranial MRI showed patchy leukoencephalopathy with cavities, involved in the corpus callosum. Follow up for 19 months-15 years that the neurology development were improved slowly in all patients. Conclusion: NDUFS1 and NDUFV1 gene mutation screening should be performed firstly in patients with PCL clinical and imaging feature.目的： 总结进行性空泡脑白质病(PCL)患儿的临床及遗传学特点。 方法： 对首都医科大学附属北京儿童医院神经内科2015至2016年临床诊断的4例PCL患儿的病例资料进行总结，并通过关键词"脑白质病""NDUFV1"或"NDUFS1""leukoencephalopathy"对中文期刊全文数据库、万方数据知识服务平台、生物医学文献数据库(Pubmed)建库至2016年8月的文献进行检索，选取临床资料完整的病例分析总结。 结果： 本组4例患儿中女3例、男1例，其中2例为同胞姐弟，起病年龄6月龄至1岁3月龄，4例均以运动倒退为首发症状，起病前发育里程碑大致正常，3例合并认知损害，1例合并癫痫，4例均存在肌张力不全合并锥体束损害，2例体形消瘦，1例有眼球震颤。4例血乳酸均正常，1例尿有机酸分析为乳酸尿。头颅磁共振成像(MRI)均提示双侧大脑半球白质广泛对称性异常信号，累及胼胝体，合并空泡样变。随访至2～13岁，运动、语言发育均较前进步。遗传学分析提示3例为NDUFS1基因变异，1例NDUFV1基因变异，共6种基因变异(NDUFV1基因的p.Arg377Cys, p．Arg377His, NDUFS1基因的p.Arg482Glyfs(*)5，p.Thr368Pro，p.Tyr454X和p.Asp565Gly)，均为未报道新变异。文献检索共收集5篇英文文献，报道10例患儿，加上本组共14例患儿。14例患儿均以运动倒退为首发症状，认知损害及肌张力障碍各11例，锥体束征阳性6例，烦躁哭闹5例，癫痫、眼球震颤各4例，斜视、吞咽困难各3例。头颅MRI均表现为弥漫性脑白质异常信号，伴空泡样变，胼胝体受累，随访至1岁7月龄～15岁，患儿神经系统功能均有缓慢进步。 结论： PCL是一种罕见的遗传代谢性疾病，对有PCL临床及影像学特点的病例，可首先进行NDUFS1及NDUFV1基因变异筛查。.