肝豆状核变性研究新进展

肝豆状核变性(WD)是由于编码铜转运的P型ATP酶基因突变而导致该酶的功能丧失，不能将铜伴侣传递而来的铜与α2球蛋白结合，导致铜蓝蛋白合成异常，胆道泌铜障碍，使游离铜增多，异常沉积于肝、脑和眼角膜，引起相应的器官脏器损伤，如肝硬化、锥体外系损伤、K-F环、溶血性贫血、肾小管损伤、肾性血尿和骨皮质变薄等改变。该文回顾了近年来WD的有关新进展，包括铜蓝蛋白、铜伴侣蛋白、ATP7B基因及相关蛋白的结构功能、基因突变及治疗，为进一步从根本上治疗WD提出可能的思路。     

肝豆状核变性研究新进展

肝豆状核变性 (WD)是由于编码铜转运的P型ATP酶基因突变而导致该酶的功能丧失 ,不能将铜伴侣传递而来的铜与α2 球蛋白结合 ,导致铜蓝蛋白合成异常 ,胆道泌铜障碍 ,使游离铜增多 ,异常沉积于肝、脑和眼角膜 ,引起相应的器官脏器损伤 ,如肝硬化、锥体外系损伤、K F环、溶血性贫血、肾小管损伤、肾性血尿和骨皮质变薄等改变。该文回顾了近年来WD的有关新进展 ,包括铜蓝蛋白、铜伴侣蛋白、ATP7B基因及相关蛋白的结构功能、基因突变及治疗 ,为进一步从根本上治疗WD提出可能的思路。     

溶血与肝豆状核变性

分析总结以溶血为首发症状的肝豆状核变性（HLD）的临床表现及特点，加深认识，提高诊疗水平，减少误诊，对50例确诊的以溶血为首发表现的HLD患儿的临床资料进行分析，结果，50例均以溶血为首发表现，均误诊为其它原因引起的溶血性贫血，误诊时间15天-6年，结果表明；对原因不明的溶血性贫血患儿，应常规查血清铜蓝蛋白及铜氧化酶，K-F环等，以便早期诊治，改善预后。     

肝豆状核变性21例

肝豆状核变性２１例（浙江省台州医院儿科３１７０００）王昕昕新乡医学院二附院儿科王家勤肝豆状核变性是常染色体遗传性疾病，儿童中比较少见。由于其临床表现多样，易引起误诊、漏诊。为了总结经验教训，减少误诊率。现将我院１９８４～１９９５年收治的２１例分析如下...     

肝豆状核变性的饮食和药物治疗

肝豆状核变性是由于ATP7B基因变异所致的一种原发性铜代谢障碍性疾病,是可治疗的遗传代谢病之一。治疗包括低铜饮食、药物及肝移植等。虽然肝豆状核变性是因为体内铜过多引起,然而,单纯限铜饮食并不能阻止疾病的进展,必须使用驱铜药物或锌剂治疗。一般建议在治疗的第一年限制富含铜的食物,病情平稳后可适当放宽对铜摄入的限制,无需严格的终身限铜饮食。过度限铜饮食有可能会引发铜缺乏,影响患者的生活质量和营养状态。药物治疗仍是肝豆状核变性治疗的基本措施,饮食治疗是重要的辅助手段。     

小儿肝豆状核变性的诊治新进展

肝豆状核变性是一种可治疗的常染色体隐性遗传病。临床以肝脏、中枢神经系统损害为主；肝铜含量测定、２４小时尿铜排泄量、角膜Ｋ－Ｆ环、血清铜蓝蛋白测定仍是诊断此病可靠的依据；基因诊断能提高此病出现症状前及无症状杂合子的诊断。影像技术对判断其发病机制、诊断及治疗转归有益。锌剂、螯合剂是治疗本病的最安全有效的方法。     

肝豆状核变性分子调控的研究进展

肝豆状核变性是一种与铜代谢相关的常染色体隐性遗传病，由ATP7B基因发生突变所致。ATP7B基因的突变种类繁多，但基因型与表型表达之间的关联甚微，目前推测这种差异系某些因子（如抗氧化蛋白1、铜代谢蛋白、X连锁凋亡抑制剂、载脂蛋白E及FK506结合蛋白52等）参与体内铜代谢调控的结果，亦即肝豆状核变性在发病学上可能存在着某些分子调控机制。该文就近期对此类分子调控的研究进展作一综述。     

不上儿肝豆状核变性的诊治新进展

肝豆状核变性是一种可治疗手常染色体隐性遗传病。临床以肝脏、中枢神经系统统损害为主；肝铜含量测定、２４小时尿铜排泄量、角膜Ｋ－Ｆ环、血清铜蓝蛋白测定仍是诊断此病可靠的依据；基因诊断能提高此病出现症状前及无症状杂合子的诊断。     

肝豆状核变性12例

肝豆状核变性 (HLD)是铜代谢障碍引起的家族性疾病 ,属常染色体隐性遗传。临床特点好发于青少年 ,以肝、脑尤其基底损害为主要临床表现。发病率约为 1/ 10 0万 ) [1] 。现将 1995～ 2 0 0 1年我院神经内科及儿科收治的 12例HLD分析如下临床资料一、一般资料　本组 12例 ,男 8例 ,女 4例 ;年龄为 6～15岁 ;病程 1个月～ 4年。 12例均符合以下条件 :1.临床表现符合HLD :如锥体外系表现 ,肝损害 ,肾损害 ,溶血症状 ,精神症状 ;2 .实验室检查 :血清铜蓝蛋白 <0 .2 g/L ,尿铜 >10 0μg/ 2 4h ;3.裂隙灯证实眼K F环存在 ;4 .有阳性家族史 ,符…     

Hypercalciuria and nephrolithiasis as a presenting sign in Wilson disease

A 9-year-old boy presented with recurrent episodes of renal colic. One year later Wilson disease was diagnosed. Evaluation of liver function and assessment of serum copper, caeruloplasmin concentration and urinary copper excretion in any child presenting with nephrolithiasis is suggested.     

Presenting symptoms and natural history of Wilson disease

The presenting symptoms of Wilson disease and its natural history as related to age are described based on 283 cases collected in Japan. The disease presented with a variety of signs and symptoms; the most frequent were in order of frequency jaundice, dysarthria, clumsiness, tremor, drooling, gait disturbance, malaise and arthralgia. The mean age at onset of the disease was 12.0 years. Hepatic and osteoarthral symptoms developed early and neurological symptoms late. Fifty-eight cases develolped neurological symptoms only, 28 cases had hepatic symptoms only, and in 26 cases hepatic mortality rate was observed in hepatic, hepato-haematological and hepato-renal cases mainly due to acute hepatic failure resulting in death only a few weeks after onset. Cases having only neurological symptoms showed a more favourable prognosis with a longer survival.     

暴发性肝衰竭型肝豆状核变性2 例报告并文献复习

目的探讨儿童暴发性肝衰竭型肝豆状核变性的临床特点,早期诊断及治疗。方法回顾2例暴发性肝衰竭型肝豆状核变性患儿的临床资料,并复习相关文献。结果 2例患儿均为女性,分别为5岁和8岁,临床表现为急性黄疸、血红蛋白尿、肝衰竭、肝性脑病、肾衰竭、心肌损伤、脏器出血,肝大,裂隙灯下K-F环阳性,符合肝豆状核变性诊断。应用DNA序列分析检测ATP7B基因外显子区域,2例患儿分别为p.P992L和p.A1063V复合杂合突变、2764del9缺失突变。结论儿童急性肝损伤应警惕暴发性肝衰竭型肝豆状核变性。     

Direct diagnosis of Wilson disease by molecular genetics

In 3 children with chronic liver disease, although multiple studies of copper metabolism were normal, which made the diagnosis of Wilson disease unlikely, analysis of ATP7B gene showed disease causing mutations in all. Molecular diagnosis should be considered in children with enigmatic liver disease, especially those with features of nonalcoholic fatty liver disease.     

肝豆状核变性的产前诊断:附3例家系报告

目的 筛查和确定肝豆状核变性（Wilson disease,WD）家系成员中的致病基因携带者与正常者, 为进一步行产前诊断或产前遗传学诊断提供信息。方法 采用外周血及羊水细胞基因组DNA抽提、PCR-RFLP、测序、微卫星等方法对WD患者进行ATP7B基因最常见突变点检测和3例产前诊断。结果 22个多子女WD家系,共生育子女47名,其中有28例患者,9例因患或高度疑似WD已故,10例表型正常。3个家系产前诊断2例杂合型,1例正常（另外1例孕5月待产）。结论 对有先证者的肝豆状核变性的家系进行普查有助于降低发病率。产前诊断有助于WD患者以及携带者的优生优育。     

Early and severe neurological features in a Wilson disease patient compound heterozygous for two frameshift mutations

We describe a patient with Wilson disease who presented at 11 years of age with neurological symptoms and subsequent rapid progression of neurological impairment but absent hepatic manifestations. Molecular analysis showed compound heterozygosity for two frameshift mutations, 2299insC and 214delAT, which most likely result in an absent or inactive protein product. Mutation-phenotypic analysis indicates that this genotype does not explain the severe phenotype, suggesting the presence of modifying factors. Conclusion Wilson disease may present even in childhood or adolescence with neurological abnormalities in the absence of hepatic manifestations. Received: 22 October 1996 / Accepted in revised form: 31 July 1997     

Oral zinc sulphate as primary therapeutic intervention in a child with Wilson disease

An 8-year-old boy with an hepatic form of Wilson disease was treated with oral zinc sulphate as the primary and sole therapy. After 4 months, liver function had dramatically improved, and the parameters characterizing copper metabolism had also normalized.Abbreviations d-pen d-penicillamine - IU international units - SCp serum ceruloplasmin - SD standard deviation - SGGT serum gamma-glutamyltransferase - SGOT serum glutamic-oxalic transaminase - SGPT serum glutamic-pyruvic transaminase     

Severely decompensated abdominal Wilson disease treated with peritoneal dialysis: A case report

A 12-year-old girl with severely decompensated abdominal Wilson disease was treated with abdominal dialysis in order to accelerate the excretion of chelated copper. Dialysate without human serum albumin or D-penicillamine was used and was able to accelerate the excretion of chelated copper, with an increment of 5.5–19.7% compared with urinary excretion only.     

与ATP7B基因紧密连锁的微卫星DNA单体型在汉族Wilson病的多态性分析

目的：了解与ATP7B基因紧密连锁的微卫星DNA(D13S314,D13S301和D13S316)单体型在正常人、Wilson病(WD)患者及其杂合子的分布特点及意义。方法：采用荧光标记3个短串联重复标记(D13S314,D13S301和D13S316),测序定位和Genotype TM 软件技术分析71例WD患者和123位父母的单体型。结果：在D13S314,D13S301和D13S316位点分析中得到71例WD患者和123位携带者及54例正常个体等位基因片段;片段大小分别为134～157 bp,128～156 bp 和136～154 bp;获得等位基因数分别为19,20和15个;3个位点的杂合率分别是 0.79,0.82 和 0.23。D13S314,D13S301和D13S316位点的等位基因分布在WD患者和正常人群之间明显不同,其中D13S314和D13S301位点显示各有9个等位基因片段存在明显差异(P<0.05),D13S316位点显示有4个等位基因片段存在明显差异(P<0.01);显示的81种单体型中以 12-6-5,15-10-5,6-10-5和6-14-5最多见,分别占 5.2%,4.5%,4.5% 和 3.7%,其次为12-8-5,12-9-5和6-16-5,各占 3.0%,13-10-8,6-13-5,6-14-13和6-9-5各占 2.2%。结论：单体型的类型较多可能和基因突变的类型多样化相关,D13S314-D13S301-D13S316的单体型分析对WD的诊断,尤其是症状前或产前诊断都有重要的意义,是有效及可行的方法之一。