儿童脑型X-连锁肾上腺脑白质营养不良的临床特点及基因突变特征

Clinical Features and Gene Mutation Characteristics of Cerebral X-Linked Adrenoleukodystrophy in Children

目的探讨儿童脑型X-连锁肾上腺脑白质营养不良的临床特点及基因突变特征。方法回顾性分析2015年1月至2020年6月就诊于郑州大学第一附属医院的11例脑型X-连锁肾上腺脑白质营养不良患儿的病历资料,包括临床特征、实验室检查、影像学特征及基因检测结果。结果11例脑型X-连锁肾上腺脑白质营养不良患儿均为男性,起病中位年龄6岁,临床表现主要为进行性视力下降、听力、智力、运动能力减退及皮肤黏膜色素沉着增加,查体可见神经系统阳性体征。3例患儿有肾上腺皮质功能不全。6例行血清极长链脂肪酸(VLCFA)测定发现二十六烷酸(C26∶O)、二十四烷酸(C24∶O)/二十二烷酸(C22∶O)、C26∶O/C22∶O升高。11例行头颅MRI检查均可见双侧对称性似蝶翼状脑白质病变,主要累及双侧顶叶、枕叶、侧脑室后角旁、胼胝体压部、大脑脚、丘脑及脑桥等部位。10例行基因检测均发现ABCD1基因致病性变异。发病后患儿神经系统症状持续加重,多数于数年后死亡。结论对脑型X-连锁肾上腺脑白质营养不良患儿,根据临床表现、特征性头颅影像学表现及VLCFA水平可以进行诊断,基因检测可明确诊断。一旦发病可在数周内迅速恶化,多在2~4 a发展至植物状态或死亡。发现了2个ABCD1基因新突变位点,丰富了ABCD1基因突变谱。

Objective To investigate the clinical features and gene mutation characteristics of cerebral X-linked adrenoleukodystrophy in children.Methods A retrospective analysis was performed to study the clinical features,laboratory examination,imaging features and gene detection results of 11 children with cerebral X-linked adrenoleukodystrophy in the First Affiliated Hospital of Zhengzhou University from January 2015 to June 2020.Results All the 11 children with cerebral X-linked adrenoleukodystrophy were male.The median age of onset was 6 years old.The main clinical manifestations were progressive loss of hearing and vision,mental retardation,athletic ability deterioration and increased skin and mucous membrane pigment.The positive signs of nervous system were found on physical examination.Three children suffered from adrenocortical insufficiency.The serum levels of very long chain fatty acid(VLCFA)including hexacosanoic acid(C26∶O),tetracosanoic acid(C24∶O)to behenic acid(C22∶O)ratio,C26∶O to C22∶O ratio were elevated in 6 cases.All 11 cases were found to have bilateral symmetric leukoencephalopathy like butterfly-wing,mainly involving bilateral parietal lobe,occipital lobe,lateral ventricle posterior horn,splenium of corpus callosum,cerebral peduncle,thalamus and pons.The pathogenic mutations of ABCD1 gene were found in 10 children who underwent genetic testing.After the onset of the disease,the neurological symptoms of children continued to worsen,and after a few years most children died.Conclusion According to the clinical manifestation,characteristic cranial imaging findings and VLCFA,the diagnosis can be made in children with cerebral X-linked adrenoleukodystrophy,and genetic testing can definitely make a diagnosis.Once the disease occurs,it can rapidly worsen within a few weeks,and most children develop into a vegetative state or death in 2 to 4 years.Two new mutation sites of ABCD1 gene are found,which enriches the mutation spectrum of ABCD1 gene.