原发性高草酸尿症1型7例临床分析  

Clinical analysis of seven cases of primary hyperoxaluria type 1

作　　者：李作林[1] 王彬 王凤梅 倪海锋[1] 刘玉秋 施雯 杨钧岚 谢筱彤 刘必成[1] 张晓良[1] Li Zuolin;Wang Bin;Wang Fengmei;Ni Haifeng;Liu Yuqiu;Shi Wen;Yang Junlan;Xie Xiaotong;Liu Bicheng;Zhang Xiaoliang(Department of Nephrology,Zhongda Hospital Southeast University,Institute of Nephrology,Southeast University,Nanjing 210009,China)

机构地区：[1]东南大学附属中大医院肾内科、东南大学肾脏病研究所,南京210009

出　　处：《中华内科杂志》2024年第8期781-786,共6页Chinese Journal of Internal Medicine

基　　金：江苏省重点研发计划社会发展项目(BE2021737,BE2023770);南京市卫生科技发展专项(YKK20237,YKK21268);国家自然科学基金(82000648);江苏省自然科学基金(BK20200363);中央高校基本科研业务费专项资金(2242023K40046);江苏省“双创”人才项目。

摘　　要：回顾性分析2018年1月至2023年10月于东南大学附属中大医院诊断为原发性高草酸尿症1型(PH 1型)患者的临床资料。7例PH 1型患者中,男4例,女3例;起病年龄26~42岁(平均32.1岁),诊断年龄28~51岁(平均40.6岁)。7例患者均以肾结石起病,3例患者起病时发现肾功能不全,其中2例患者发现时即进行血液透析。就诊时的症状包括骨痛7例,关节疼痛或关节畸形5例,乏力5例,低血压3例,皮下结节2例。4例患者有家族史。7例患者血红蛋白60~114 g/L,白蛋白16.5~32.1 g/L,D-二聚体2230~12781μg/L。7例患者已行维持性血液透析,行透析年龄26~50岁(平均37.7岁),自起病至进入透析时长为0~20年(平均5.6年)。5例患者反复发生透析通路功能不良。3例患者在明确诊断前行肾移植,移植肾均因草酸盐沉积而失去功能。随访4~38个月(平均14.43个月),死亡1例。7例患者均行腹部CT检查,可见骨骼病变、双侧肾脏多发结石和肾钙质沉着表现。6例患者检出AGXT基因突变,其中复合杂合变异4例,单纯纯合变异2例。变异位点为c.823-824dup.AG(p.S275Rfs*38)(exon 8)、c.815-816ins.GA(p.S275Rfs*38)(exon 8)、c.595G>A(p.G199S)(exon5)、c.32C>G(p.P11R)(exon1)、c.638C>T(p.A213V)(exon 6);经美国医学遗传学与基因组学会分级判定2个位点为可能致病变异,7个位点为致病变异,1个位点为意义未明。4例患者行组织活检,病理均表现出大量草酸盐沉积。PH 1型是一种罕见的常染色体隐性遗传病,深入理解PH 1型患者的临床特征,对早诊断早治疗具有十分重要的意义。We retrospectively analyzed the clinical data of seven patients(four men and three women)with primary hyperoxaluria(PH)type 1(PH1)in the Department of Nephrology of Zhongda Hospital,Southeast University from January 2018 to October 2023.The mean age at disease onset was 32.1(range:26-42)years.The mean age at diagnosis was 40.6(range:28-51)years.All patients initially had kidney stones,and three patients were found to have renal insufficiency at the time of disease onset.Among them,two patients underwent hemodialysis immediately.Symptoms at the first visit included bone pain(n=7),joint pain or deformity(n=5),fatigue(n=5),hypotension(n=3),and subcutaneous nodules(n=2).Four patients had a family history of PH.All patients had varying degrees of anemia(60-114 g/L),significant hypoalbuminemia(16.5-32.1 g/L),and hypercoagulable state(D-dimer:2230-12781μg/L).Seven patients received maintenance hemodialysis;their mean age was 37.7(range:26-50)years.The mean duration from disease onset to hemodialysis was 5.6(range:0-20)years.Five patients repeatedly experienced dialysis access dysfunction.Three patients underwent kidney transplantation before a diagnosis was made,and all transplanted kidneys lost function due to oxalate deposition.The mean follow-up duration was 14.43(range:4-38)months.Unfortunately,one patient died.All seven patients underwent computed tomography of the abdomen.All patients suffered skeletal abnormalities,bilateral nephrolithiasis,and nephrocalcinosis.Six patients carried AGXT gene mutations,including four compound heterozygous mutations and two pure homozygous mutations.The mutation sites included:c.823-824dup.AG(p.S275Rfs*38)(exon 8),c.815-816ins.GA(p.S275Rfs*38)(exon 8),c.595G>A(p.G199S)(exon 5),c.32C>G(p.P11R)(exon 1),and c.638C>T(p.A213V)(exon 6).According to the American College of Medical Genetics and Genomics guidelines,two loci were identified as likely pathogenic variants,seven were identified as pathogenic variants,and one locus was identified as having uncertain significance.In addition,pat

关 键 词：高草酸尿症 原发性 遗传性疾病 高凝状态 顽固性低白蛋白血症 多器官病变 

分 类 号：R596[医药卫生—内科学] R696[医药卫生—临床医学]