摘要
目的探讨EARS2基因突变致丘脑脑干受累性脑白质病伴高乳酸血症(LTBL)的临床特征、实验室检查特点及基因型,提高对该病的认识和管理水平。方法总结和分析1例以肝功能衰竭为首发表现的LTBL病例的临床特点、实验室检查、基因检测结果及随访,并行文献复习。结果男,45 d,因"皮肤黄染43 d"就诊。患儿生后2 d发现皮肤、巩膜黄染,42 d后发现肝功能衰竭(严重胆汁淤积、低血糖、凝血功能异常)、四肢肌张力减低,高乳酸性酸中毒;颅脑MR提示多发脑损伤;外显子捕获与高通量测序检测线粒体基因未见异常,检测核基因发现16号染色体上EARS2基因存在2个致病性复合杂合突变[c.1355T>G(p.L452R),c.813C>A(p.F271L)],确诊为LTBL。随访中黄疸逐渐消退,15月龄时肝功能检查恢复正常,血乳酸水平降至正常;精神运动发育明显落后,颅脑MR提示严重脑积水,予以行脑室-腹腔引流术,术后半年脑积水好转,精神运动发育较前改善。结论肝功能衰竭可以是EARS2基因突变所致的LTBL早期主要发现之一,随着年龄增长,肝功能可逐渐好转,精神运动发育落后及脑积水逐渐成为本病较为显著的临床特点,LTBL表型和基因型的关系还需要进一步研究。
Objective To explore the genotype and clinical characteristics of the leukoencephalopathy with thalamus and brainstem involvement and high lactste(LTBL)caused by the mutation of EARS2 gene,and to improve the understanding of the disease.Methods The clinical characteristics,laboratory examination and genetic testing of one case of LTBL were presented,analyzed and discussed.The related literatures were reviewed.Results The male case presented jaundice from the second day after birth.Liver failure(severe cholestasis,hypoglycemia and dysfunction of blood coagulation),typical LTBL clinical features including severe lactic acidosis,growth and mental retarration besides hypoglycemia were found after the age of 42 days.Brain MR revealed multiple brain injury.Genetic sequencing from the child and his parents revealed compound heterozygous variants in EARS2 gene:c.1355T>G(p.L452R)and c.813C>A(p.F271L).At the age of 15 months old,biochemical markers(including liver enzymes,bilirubin,blood glucose and lactic acid)were completely normal and delayed psychomotor development was obvious.Brain MR showed severe hydrocephalus.Hydrocephalus and delyed motor development improved greatly after 6 months of ventriculo-peritoneal drainage.Conclusion Liver failure is one of the early major manifestations of LTBL caused by gene mutation in EARS2.With age,hydrocephalus may be one of the clinical features of this disease.EARS2 gene mutations of c.1355T>G(p.L452R)and c.813C>A(p.F271L)are the pathogenic gene mutations of LTBL.The clinical features and genotypes of LTBL should be further studied.
作者
康美华
朱贤
谢新宝
杨皓玮
方微园
陆怡
王建设
KANG Mei-hua;ZHU Xian;XIE Xin-bao;YANG Hao-wei;FANG Wei-yuan;LU Yi;WANG Jian-she(Department of Pediatrics,The Central Hospital of Xiangtan,Xiangtan 411100,China;Children's Hospital of Fudan University,Shanghai 201102,China)
出处
《中国循证儿科杂志》
CSCD
北大核心
2018年第4期285-289,共5页
Chinese Journal of Evidence Based Pediatrics
