以Addison病为首发表现的肾上腺脑白质营养不良症一例及ABCD1基因新突变分析  

Addison disease as presenting manifestation of one patient with adrenoleukodystrophy and identification of a novel ABCD1 gene mutation

作　　者：周月 董冰子 王翔[1] 耿壮 黄雅静 王颜刚[1] Zhou Yue;Dong Bingzi;Wang Xiang;Geng Zhuang;Huang Yajing;Wang Yangang(Department of Endocrinology,Affiliated Hospital of Qingdao University,Qingdao 266003,China)

机构地区：[1]青岛大学附属医院内分泌科,266003

出　　处：《中华内分泌代谢杂志》2019年第10期829-833,共5页Chinese Journal of Endocrinology and Metabolism

基　　金：山东省自然科学基金资助项目(ZR2014HM021)。

摘　　要：目的报道1例少见的以肾上腺皮质功能减退(Addison病)为首发表现的肾上腺脑白质营养不良症的临床、影像学及基因突变特点。方法详细收集先证者及家系成员的临床资料,采用高通量测序法对先证者及母亲进行ATP-结合盒D亚组膜1(ABCDl)基因测序。结果患者早期表现为全身皮肤色素沉着伴乏力,发热时引发卒中样发作,主要表现为突发性意识丧失及二便失禁,进行性发展为言语不清、行走不稳及视力下降。血清极长链脂肪酸浓度增高。头颅MRI显示双侧胼胝体压部对称性分布的异常信号。患者的ABCDl基因检测到c.874_876del GAG的新半合子变异,其母亲存在同位点的核苷酸杂合变异。结论肾上腺脑白质营养不良的诊断需要结合临床表现、影像学检查及血清极长链脂肪酸水平测定,ABCD1基因突变分析是明确诊断最可靠的方法。Objective To identify the clinical manifestations,imaging findings,and genetic mutation characteristics in a rare case of adrenoleukodystrophy(ALD)with adrenocortical dysfunction(Addison′s disease)as the first manifestation.Methods The clinical data of the proband and his family members were comprehensively collected,and ABCDl gene sequencing was meticulously performed for the proband and his mother using high-throughput sequencing method.Results The patient presented with systematical skin pigmentation accompanied by fatigue in early stage,arose stroke-like episodes manifested as a sudden loss of consciousness and incontinence induced by high fever,and followed by progressive unclear speech,unstable walking and worsening vision.Serum very long-chain fatty acid(VLCFA)concentration increased over normal range.The brain MRI showed an abnormal signal of the symmetric distribution of the bilateral corpus callosum.A new c.874_876del GAG hemizygous variation in the patient′s ABCD1 gene was detected,while his mother had a nucleotide heterozygous variation to this site.Conclusion The diagnosis of ALD requires a combination of clinical manifestations,imaging examination,and serum VLCFA level measurement,while the detection of ABCD1 gene mutations is considered to be the most reliable approach.

关 键 词：肾上腺脑白质营养不良 肾上腺皮质功能不全 ADDISON病 ABCD1基因 

分 类 号：R73[医药卫生—肿瘤]