一个以痛风为首发表现的糖原累积病Ⅰa型家系的临床特点和遗传学分析  

Clinical characteristics and genetic analysis of a Chinese pedigree affected by glycogen storage disease typeⅠa with gout as the first manifestation

作　　者：李谦华[1] 郑慕晗 李晓娟[3] 欧阳志明[1] 韦秀宁[1] 郑东辉[1] 戴冽[1] Li Qianhua;Zheng Muhan;Li Xiaojuan;Ouyang Zhiming;Wei Xiuning;Zheng Donghui;Dai Lie(Department of Rheumatology,Sun Yat-Sen Memorial Hospital,Sun Yat-Sen University,Guangzhou,Guangdong 510120,China;Shenshan Medical Center,Memorial Hospital of Sun Yat-Sen University,Shanwei,Guangdong 516600,China;Cellular&Molecular Diagnostics Centre,Sun Yat-Sen Memorial Hospital,Sun Yat-Sen University,Guangzhou,Guangdong 510120,China)

机构地区：[1]中山大学孙逸仙纪念医院风湿免疫科,广州510120 [2]中山大学孙逸仙纪念医院深汕中心医院风湿内科,广东516600 [3]中山大学孙逸仙纪念医院细胞分子诊断中心,广州510120

出　　处：《中华医学遗传学杂志》2022年第9期983-987,共5页Chinese Journal of Medical Genetics

摘　　要：目的探讨一个以痛风为首发表现的糖原累积病(glycogen storage disease,GSD)Ⅰa型家系的临床及遗传学特点。方法收集一例GSDⅠa型先证者的家系资料,进行基因测序查找其变异位点,利用生物信息学软件分析变异位点的意义,并对其进行5年的随访观察。结果先证者为年轻女性,以反复痛风发作、低血糖、高甘油三酯为主要表现,弟弟还表现为发育异常和肝腺瘤。基因测序发现先证者和弟弟G6PC基因均存在2个杂合变异:c.1022T>A(p.I1e341Asn)及c.230+5G>A,分别遗传自其父亲和母亲。其中变异c.230+5G>A为内含子区变异,既往未见报道,生物信息学分析显示该变异危害G6PC基因mRNA剪接。先证者经生玉米淀粉、别嘌醇、非诺贝特治疗后病情控制良好,并生下一个无GSD表现女婴。结论对于合并低血糖、肝脏肿大的青年痛风患者须考虑GSDⅠa型可能,应进行基因检测明确。GSDⅠa型经饮食和药物综合治疗预后良好。Objective To explore the clinical and genetic characteristics of a Chinese pedigree affected by glycogen storage disease(GSD)typeⅠa with gout as the first manifestation.Methods Clinical and biochemical data of the pedigree were collected.Available members of the pedigree were subjected to gene sequencing,and the result was analyzed by bioinformatic software.The pedigree was followed up for five years.Results The proband was a young female manifesting recurrent gout flare,hypoglycemia,and hypertriglyceridemia.One of her younger brothers also presented with dysplasia and hepatic adenoma.Gene sequencing revealed that the proband and her younger brother both harbored c.1022T>A(p.I1e341Asn)and c.230+5G>A compound heterozygous variants of the G6PC gene,which were inherited from their father and mother,respectively.Among these,the c.230+5G>A is an intronic region variant which was unreported previously,and bioinformatic analysis showed that it may impact mRNA splicing of the gene.The proband was treated with raw corn starch,allopurinol,and fenofibrate.Gout was well controlled,and she had given birth to a baby girl without GSD.Conclusion GSDⅠa should be considered among young gout patients with hypoglycemia and hepatomegaly,for which gene sequencing is warranted.GSDⅠa has a good prognosis after comprehensive treatment with diet and medicine.

关 键 词：糖原累积病 G6PC基因 痛风 低血糖 

分 类 号：R589.7[医药卫生—内分泌]