X连锁肾上腺脑白质营养不良89例临床特征及基因型/表型关系  

Clinical features and genotype-phenotype studies of 89 Chinese patients with X-linked adrenoleukodystrophy

作　　者：平莉莉[1] 包新华[1] 王爱花[1] 潘虹[1] 吴晔[1] 熊晖[1] 姜玉武[1] 秦炯[1] 吴希如[1] 

机构地区：[1]北京大学第一医院儿科,100034

出　　处：《中华儿科杂志》2007年第3期203-207,共5页Chinese Journal of Pediatrics

基　　金："十五"国家科技攻关计划(2004BA720A03);卫生部属医疗机构临床学科重点项目(20010912)

摘　　要：目的研究 X 连锁肾上腺脑白质营养不良(X-ALD)患者的临床特征、基因突变模式及基因型/临床表型关系。方法对89例 X-ALD 患者的病例资料进行综合分析。应用 PCR 扩增和DNA 直接测序方法对其中53例进行 ABCD1基因突变分析。结果 89例患者中,儿童脑型60例(发病年龄2～10岁,平均6.5岁,占67.4%),青少年脑型18例(发病年龄11～19岁,平均12岁,占20.2%),肾上腺脊髓神经病型7例(发病年龄6～39.5岁,平均23岁,占7.0%),单纯艾迪生病2例,无症状者2例。临床表型以儿童脑型最常见。首发症状以视力、听力下降最常见。在53例患者中发现45种不同类型的 ABCD1基因突变,以错义突变为主。国外突变"热点"即外显子5的突变1415delAG 不是中国人群的突变热点。同样突变可以导致截然不同的临床表型,即使同一家系也存在不同临床表型的患者。同样表型也可以由截然不同的基因突变所致。结论中国 X-ALD 患者的表型分布、首发症状、基因突变模式等方面与国外报道不完全相同。基因型和临床表型无明确相关性。Objective X-linked adrenoleukodystrophy （X-ALD） is the most common inherited disorder of peroxisomal metabolism which is characterized by demyelination of central nervous system, impaired adrenal cortex and abnormal accumulation of very long chain fatty acids in body fluid and tissues. In this study, the clinical features and the genotype-phenotype relationship were investigated so as to help early diagnosis. Methods Clinical data of 89 Chinese patients with X-ALD were analyzed and mutation spectrums in 53 of the patients were investigated by polymerase chain reaction and DNA sequencing. Results Of the 89 cases, 60 （67.4%） had childhood cerebral ALD （ CCALD, mean age of onset was 6. 5 years, range 2 -10 years）, 18 （20. 2% ） had adolescent cerebral ALl） （ACALD, mean age of onset 12. 1 years, range 11 -19 years）, 7 （7.9%） had adrenomyeloneuropathy （AMN, mean age of onset 23 years, range 6-39.5 years）, and two cases were asymptomatic and another 2 had simple Addison＇s disease only. CCALD was the most common and severe phenotype, visual impairment was the most common initial symptom in CCALD and ACALD patients. Twenty four eases （63%） in whom hydrocortisone and ACTH were measured showed adrenal insufficiency. Forty five different mutations were identified in 53 patients. Missense mutations were the most common. No hotspot mutation was found in these patients and 1415delAG, the most frequent mutation found worldwide seemed not to be the real ＂hotspot＂ in these Chinese patients. The same phenotype may be due to diverse genomic mutations. A single mutation may result in different phenotypes even within a family. Conclusion The phenotype distribution, initial symptom and gene mutation spectrum of Chinese patients may not be completely consistent with those in other countries. The clinical phenotype of the disease had no definite relationship with the nature of gene mutations.

关 键 词：肾上腺脑白质营养不良 基因型 表型 ATP结合匣式转运子 突变 

分 类 号：R742.8[医药卫生—神经病学与精神病学]