X-连锁肾上腺脑白质营养不良表型及基因型研究

Study on the phenotype and genotype of X-linked adrenoleukodystrophy

目的总结分析X-连锁肾上腺脑白质营养不良(X-ALD)患者的表型和基因型,比较儿童和成人X-ALD患者的表型和基因型特点。方法收集2012年8月至2019年12月在北京京都儿童医院和解放军总医院诊断或转诊的30例经临床确诊的X-ALD患者,对其临床表现、基因检测结果、生化和影像学检查结果等进行综合分析。结果30例患者中共有儿童脑型ALD(CCALD)15例(50.0%;发病年龄5~10岁,平均7岁),肾上腺脊髓神经病型(AMN)13例(43.4%;发病年龄21~41岁,平均29岁),成人脑型ALD 1例(3.3%;发病年龄29岁),单纯Addison病型1例(3.3%;发病年龄3.5岁)。儿童患者临床表型以CCALD最常见,首发症状以注意力不集中、学习能力下降、视力听力障碍为主;成年起病的以AMN最常见,首发症状主要为进行性双下肢无力、肌肉痉挛、步态异常。30例患者来自29个不同的家系,其中有25例进行了基因检测,发现了22种不同类型的ABCD1基因突变,突变类型以错义突变为主,不同临床分型的患者在基因突变类型上没有特异性。结论中国X-ALD患者儿童和成人在发病年龄和临床表型上有不同的特点:儿童临床分型以CCALD最为常见,而成人以AMN最常见;儿童和成人X-ALD患者其基因型与表型之间均没有发现明确的相关性。

Objective To summarize the phenotype and genotype of X-linked adrenoleukodystrophy(X-ALD)patients,and compare the phenotype and genotype characteristics between children and adult patients.Methods The comprehensive clinical data of 30 patients with X-ALD admitted to Beijing Jingdu Children′s Hospital and the First Medical Center of People′s Liberation Army General Hospital from August 2012 to December 2019 were analyzed,including their clinical manifestations and the results of gene test,biochemical test and magnetic resonance imaging examination,etc.Results Among the 30 patients,15(50.0%)were childhood cerebraI ALD(CCALD,onset age 5-10 yeas,mean 7 years),13(43.3%)were adrenomyeloneuropathy(AMN,onset age 21-41 yeas,mean 29 years).One(3.3%)was adult cerebral ALD(onset age 29 yeas),one(3.3%)was pure Addison disease(onset age 3.5 yeas).Most common clinical phenotype in children was CCALD and the first symptoms were inattention,learning ability decline,vision and hearing impairment.Otherwise the most common type in adult was AMN and the first symptoms were mainly progressive weakness of the lower limbs,muscle spasm,and abnormal gait.These patients came from 29 different families,among whom,25 patients conducted gene test and 22 different types of ABCD1 gene mutations were found.Missense mutation was the main gene mutation type.Patients with different clinical types had no specificity in gene mutation types.Conclusions In China,the most common clinical classification of X-ALD in children is CCALD,and AMN in adults.No clear correlation has been found between genotype and phenotype.