戊二酸尿症1型的复杂临床表型与基因型  

Complex heterogeneity phenotypes and genotypes of glutaric aciduria type 1

作　　者：王峤[1] 杨艳玲[1] 

机构地区：[1]北京大学第一医院儿科,北京100034

出　　处：《中国当代儿科杂志》2016年第5期460-465,共6页Chinese Journal of Contemporary Pediatrics

基　　金："十二五"国家科技支撑计划项目(2012BAI09B04);儿科遗传性疾病分子诊断与研究北京市重点实验室(Z141107004414036)

摘　　要：戊二酸尿症1型为罕见的有机酸尿症,为常染色体隐性遗传病。戊二酰辅酶A脱氢酶(GCDH)基因缺陷导致戊二酰辅酶A脱氢酶活性降低或缺陷,导致戊二酸、3-羟基戊二酸在体内蓄积,引起纹状体等神经核团损害,导致神经退行性疾病。患者临床表型及基因型复杂,个体差异显著,胎儿期至成年均可发病,轻症患者发病前几乎无临床症状,重者表现为严重的急性代谢性脑病,导致死亡或残障。婴幼儿时期常因发热、外伤、饥饿、高蛋白饮食、疫苗接种等诱因引发急性脑病。患者发病年龄越早症状越重,预后越差。尿有机酸、血液酯酰肉碱谱分析及GCDH基因检测是诊断戊二酸尿症1型的重要方法,新生儿筛查是早期诊断、改善预后的关键。Glutaric aciduria type 1 is a rare autosomal recessive disorder.GCDH gene mutations cause glutarylCo A dehydrogenase deficiency and accumulation of glutaric acid and 3-hydroxyglutaric acid,resulting in damage of striatum and other brain nucleus and neurodegeneration.Patients with glutaric aciduria type 1 present with complex heterogeneous phenotypes and genotypes.The symptoms are extremely variable.The ages of the clinical onset of the patients range from the fetus period to adulthood.The patients with mild glutaric aciduria type 1 are almost asymptomatic before onset,however,severe glutaric aciduria type 1 may cause death or disability due to acute encephalopathy.Acute metabolic crisis in patients with underlying glutaric aciduria type 1 is often triggered by febrile illnesses,trauma,hunger,high-protein foods and vaccination during a vulnerable period of brain development in infancy or early childhood.The early-onset patients usually have a poor prognosis.Urinary organic acids analysis,blood acylcarnitines analysis and GCDH study are important for the diagnosis of this disorder.Neonatal screening is essential for the early diagnosis and the improvement of prognosis.

关 键 词：戊二酸尿症1型 戊二酰辅酶A脱氢酶 肌张力不全 有机酸尿症 新生儿筛查 

分 类 号：R725.9[医药卫生—儿科]