一例肾上腺脑白质营养不良症的临床特点及ABCD1基因新突变分析  

Clinical characteristics of adrenoleukodystrophy with a novel ABCD1 gene mutation

作　　者：闫涵 薛冰霜 杨奇超[1,2] 韦玉和 邵雪景[1,2] Yan Han;Xue Bingshuang;Yang Qichao;Wei Yuhe;Shao Xuejing(Department of Endocrinology,Wujin Hospital Affiliated to Jiangsu University,Changzhou 213000,China;Department of Endocrinology,the Wujin Clinical College of Xuzhou Medical University,Changzhou 213000,China)

机构地区：[1]江苏大学附属武进医院内分泌科,常州213000 [2]徐州医科大学武进临床学院内分泌科,常州213000

出　　处：《中华内分泌代谢杂志》2023年第10期833-838,共6页Chinese Journal of Endocrinology and Metabolism

基　　金：2022年度常州市卫健委科技项目(WZ202226)资助。

摘　　要：目的探讨肾上腺脑白质营养不良症(ALD)患者的临床特点和遗传学病因。方法以1例进行性双下肢无力为首发症状的ALD患者为研究对象(先证者),收集该先证者及其家系成员的临床资料,以高通量测序法对先证者及其3个女儿进行ATP-结合盒D亚组膜1(ABCDl)基因测序和突变分析。结果先证者发病年龄晚,病程长,早期表现为双下肢无力、夜间肌肉痉挛,进行性发展为痉挛性四肢瘫痪、失语、痴呆、吞咽困难、二便失禁。血清极长链脂肪酸浓度增高,糖皮质激素的亚临床分泌异常。头颅影像学检查提示双侧侧脑室周围脑白质区密度对称性减低,脑白质变性。先证者的ABCDl基因检测到c.1367G>A,p.R456H的新半合子变异。其3个女儿存在同位点的核苷酸杂合变异。结论本研究探讨了ALD的临床特点,为该类患者的诊疗提供更多的临床依据。同时发现ABCD1基因的一处新变异,丰富了ALD致病基因的遗传变异数据库。Objective To analyze the clinical features and genetic background of adrenoleukodystrophy(ALD).Methods In this study,we reported a rare case of ALD who initially presented with progressive bilateral lower limb weakness.The clinical data of the patient and his family members were collected and the ABCD1 gene was sequenced for the patient and his three daughters by a high-throughput sequencing method.Results The proband had a later onset of symptoms,a prolonged course of the disease,and initially exhibited bilateral lower limb weakness and nocturnal muscle spasms.The disease progressed to spastic quadriplegia,aphasia,dementia,swallowing difficulties,and urinary and fecal incontinence.Serum very-long-chain fatty acid concentrations were elevated.Subclinical cortisol secretion abnormalities were observed.Cranial imaging indicated symmetrical reduction in density around the lateral ventricles and white matter degeneration.The proband′s ABCD1 gene analysis revealed a novel heterozygous mutation c.1367G>A,p.R456H.His three daughters carried the same nucleotide heterozygous mutation.Conclusion This study investigates the clinical characteristics of ALD,providing additional clinical evidence for the diagnosis and treatment of this condition.Additionally,a novel mutation in the ABCD1 gene was identified,contributing to the genetic variation database.

关 键 词：肾上腺脑白质营养不良 罕见病 基因突变 ABCD1基因 

分 类 号：R586[医药卫生—内分泌]