GLA基因变异致法布雷病家系分析  

Genotype-phenotype analysis of Fabry disease caused by GLA gene variation in a pedigree

作　　者：葛主辉 路智红[2] 潘晓丹 赖婷婷 杨妙娟 杨华琴 章惠彬 李光银 戴张峤 毛建华[2] Ge Zhuhui;Lu Zhihong;Pan Xiaodan;Lai Tingting;Yang Miaojuan;Yang Huaqin;Zhang Huibin;Li Guangyin;Dai Zhangqiao;Mao Jianhua(Department of Pediatrics,Ninghai First Hospital,Ninghai 315600,China;Department of Nephrology,the Children′s Hospital,Zhejiang University School of Medicine,National Clinical Center for Child Health,Hangzhou 310052,China;Department of Cardiology,Ninghai First Hospital,Ninghai 315600,China;Department of Infectious Diseases,Ninghai First Hospital,Ninghai 315600,China;Department of Nephrology,Ninghai First Hospital,Ninghai 315600,China;Department of Ultrasound,Ninghai First Hospital,Ninghai 315600,China)

机构地区：[1]浙江省宁海县第一医院儿科,宁海315600 [2]浙江大学医学院附属儿童医院,国家儿童健康与疾病临床医学研究中心,杭州310052 [3]浙江省宁海县第一医院心内科,宁海315600 [4]浙江省宁海县第一医院感染科,宁海315600 [5]浙江省宁海县第一医院肾脏内科,宁海315600 [6]浙江省宁海县第一医院超声科,宁海315600

出　　处：《中华儿科杂志》2024年第4期345-350,共6页Chinese Journal of Pediatrics

基　　金：宁波市医学科技计划(2020Y76);宁海县科技计划(2023025)。

摘　　要：目的总结GLA基因IVS4+919G>A变异致法布雷病一家系的临床表型和遗传学特征。方法前瞻性筛查研究。2021年10月至2023年8月对宁海县102例法布雷病高危患儿进行筛查,采用干纸血片试验法,α-半乳糖苷酶活性<2.40μmol/(L·h)或脱乙酰基三己糖酰基鞘脂醇浓度>1.10μg/L的患儿接受GLA基因变异检测进一步确诊,并通过先证者进行家系筛查。以成功确诊的1例法布雷病先证者及家系作为研究对象,对GLA基因IVS4+919G>A变异致法布雷病患儿的临床表型和遗传特征进行总结。结果102例患儿中共确诊1例罕见的以双下肢疼痛为首发症状,携带GLA基因IVS4+919G>A变异的9.8岁女性法布雷病先证者。通过家系筛查发现该家系中4例成员(先证者父亲、姐姐、姑表姐、姑表兄)可确诊为法布雷病,1例成员(五姑母)为变异基因携带者,其中先证者姑表兄13.2岁,携带GLA基因IVS4+919G>A变异,以间歇性双下肢疼痛为首发症状;先证者父亲有膝关节疼痛;先证者姐姐及五姑母有视力下降;先证者姑表姐无明显症状。结论儿童高危筛查及家系筛查对法布雷病的早诊早治有重要意义,GLA基因IVS4+919G>A变异致法布雷病早期可出现周围神经性疼痛。Objective To investigate the clinical phenotype and genetic characteristics of patients with Fabry disease caused by a GLA variant,IVS4+919G>A.Methods It was a prospective study.Fabry disease screening was conducted among high-risk population in Ninghai from October 2021 to August 2023.Those children with decreasedα-galactosidase enzyme activity<2.40μmol/(L·h)or elavated Lyso-GL-3 level>1.10μg/L in dried blood spot(DBS)method underwent GLA genetic testing for diagnosis confirmation.Meanwhile,family screening was carried out.A proband and his family members diagnosed with Fabry disease were research subjects.The clinical and genetic characteristics of patients with Fabry disease caused by the GLA variant(IVS4+919G>A)were analyzed.Results The female proband aged 9.8 years with pain in both lower limbs as the initial symptom was found to have a heterozygous GLA variant IVS4+919G>A among 102 patients.In family screening,there were 4 family members(proband's father,elder sister,elder male cousin and elder female cousin)with Fabry disease and a family member(proband's fifth aunt)with a GLA variant.Among these 4 diagnosed family members,the elder male cousin of the proband,a boy aged 13.2 years had a heterozygous GLA variant,IVS4+919G>A with intermittent pain in both lower limbs as the initial symptom.The proband′s father had knee joint pain.The proband′s elder sister had decreased vision and his elder female cousin had no obvious symptoms.The proband′s fifth aunt with a GLA variant had decreased vision.Conclusions High-risk screening in children and family screening are helpful for early diagnosis and treatment of Fabry disease.Neuropathic pain may be a early symptom in children with Fabry disease caused by the GLA variant,IVS4+919G>A.

关 键 词：早期诊断 基因 疼痛 儿童 法布雷病 

分 类 号：R725.4[医药卫生—儿科]