GBA基因复合杂合型突变导致罕见戈谢病Ⅱ型患儿1例  

A case of Gaucher disease Type 2 due to compound heterozygous mutations in GBA gene

作　　者：孙芳[1] 鲁伟 朱敏 杨艳玲[4] 许鹏飞[1] SUN Fang;LU Wei;ZHU Min;YANG YanLing;XU PengFei(Department of Pediatrics,China-Japan Friendship Hospital Beijing 100029,China;Department of Pediatrics,Shunyi Maternal and Children＇s Hospital of Beijing Children ＂s Hospital Beij＇ing 101300,China;Department of Pediatrics,The Hospital of Traditional Chinese Medicine ofRongshui Miao Autonomous County,Liuzhou 545300,China;Department of Pediatrics,Peking University First Hospital,Beijing 100034,China)

机构地区：[1]中日友好医院儿科,北京100029 [2]北京儿童医院顺义妇儿医院儿科.北京101300 [3]广西壮族自治区柳州市融水苗族自治县中医医院儿科,柳州545300 [4]北京大学第一医院儿科,北京100034

出　　处：《中国科学：生命科学》2018年第10期1093-1100,共8页Scientia Sinica(Vitae)

摘　　要：本研究旨在探讨戈谢病Ⅱ型的临床特点及诊断思路.先证者,女, 1岁1个月时因"营养不良,智力运动倒退"来院.患儿生后"嗓子呼噜,痰多",疑诊断"喉喘鸣"; 6个月后体重增长缓慢,被诊断"营养不良"; 9个月后智力运动倒退,接受康复训练无效; 1岁1个月时发现脾肿大、贫血、血小板减少,并出现惊厥发作,来院进行病因分析.外周血白细胞葡萄糖脑苷脂酶(GBA)活性显著减低(0.4 nmol g^(-1)min^(-1),正常对照2.63～25.6 nmol g^(-1)min^(-1)),血浆壳三糖酶活性显著升高(54000.5 nmol L^(-1)min^(-1),正常对照0～25145 nmol L^(-1)min^(-1)).靶向捕获二代测序法及Sanger测序法验证对患儿GBA基因进行分析发现已知致病的复合杂合突变, c.703T>C(p.S235P)和c.1205A>G(p.Y402C),两个突变分别来自父母,确诊为戈谢病Ⅱ型.患儿1岁4个月在家中"呛奶",窒息死亡.戈谢病是一种常染色体隐性遗传代谢病,Ⅱ型为罕见的类型,预后差.本文患儿隐匿起病,诊断过程曲折,经外周血白细胞溶酶体酶活性分析及基因分析才获得诊断.This study aimed to explore the clinical features and diagnostic strategy of Gaucher disease type 2. The female proband was hospitalized at the age of 13-month-old because of malnutrition and psychomotor regression. She presented ＂snoring from throat and profuse sputum＂ after birth and was suspected as ＂laryngeal stridor＂. Malnutrition was observed because of failure to thrive from the age of 6 months. Since the age of 9 months, she presented with mental and motor regression. Rehabilitation training was not effective. When she was 13 months old, splenomegaly, anemia, thrombopenia, and convulsion were noticed. The glucocerebrosidase （GBA） activity of her fresh peripheral leucocytes was significantly decreased （0.4 nmol g~ min~, normal control 2.63-25.6 nmol gt mini）, while the activity of chitotriosidase was increased greatly （54000.5 nmol L-1 rain-1, normal control 0-25145 nmol L-1 min-~）. In her GBA gene, two pathogenic compound heterozygous mutations, c.703T〉C （p.S235P） and c.1205A〉G （p.Y402C）, were detected by target genomic DNA capture for next generation sequencing method and validated by Sanger sequencing method. Each parent carried one mutation. The results confirmed the diagnosis of Gaucher disease type 2. Unfortunately, the girl died of asphyxia at the age of 16 months due to milk choking at home. Gaucher disease is a disorder of inborn error of metabolism inherited as autosomal recessive mode due to GBA mutations. Type 2 is the rare type of the disease with poor prognosis. In this study, the girl with occult onset had experienced difficult diagnostic process. Analysis of lysosomal enzyme activities and gene studies are keys for the diagnosis.

关 键 词：戈谢病 遗传代谢病 脾肿大 葡萄糖脑苷脂酶 GBA基因 

分 类 号：R725.9[医药卫生—儿科]