摘要肝豆状核变性为少见、可用药物治疗、深受关注的遗传性疾病,及时、准确的诊断至关重要.本文介绍本病诊断方面最新进展及其作者多年的经验.临床和常规检查的特点是:年龄范围广,低龄和高龄均不能排除本病;症状轻而体征重,转氨酶和胆红素变化轻而白蛋白和凝血功能变化重等是筛查本病的线索;碱性磷酸酶/总胆红素＜2和门冬氨酸氨基转移酶/丙氨酸氨基转移酶＞2.2有助于暴发型的诊断.在我国,K-F环平均阳性率为72.2％,脑型阳性率为93.4％,显著高于肝型的63.3％,6岁以下儿童少有阳性.铜蓝蛋白阳性率为98.9％,平均为(71.1±48.7) mg/L,约75％患者＜100 mg/L,其中约50％患者＜50 mg/L.但50％其他原因的肝衰竭患者铜蓝蛋白也可降低,肾病综合征可低于50 mg/L;基础尿铜敏感性为86.7％,特异性为78.3％,驱铜试验敏感性(70％)低于基础尿铜;而特异性(97.0％)显著高于基础尿铜.肝铜为诊断本病的金标准,最佳临界值为210μg/g,敏感性为98.9％,特异性为96.0％;近年基因检查技术发展很快,全外显子序列分析已普及,阳性率达90％,特异性几乎为100％;定量诊断是根据诊断指标异常程度将其量化,根据积分判断诊断的可能性,积分≥4,本病可能性大;积分≤1分,可排除本病.定量诊断对于不典型患者和缺乏经验的医生特别有用.但是,如未进行肝铜和基因检查,低积分不能排除本病,慢性胆汁淤积性肝病和本病杂合子合并其他疾病偶尔可≥4,引起假阳性.

abstractsWilson disease (WD) is a rare and treatable genetic disorder.This paper describes the new advances and author's long-term experiences in the diagnosis of WD.The characteristics in clinical and routine tests are:the age of presentation can be quite broad,the WD could not be excluded based on age only;the patients usually have mild digestive symptoms but obvious chronic liver disease signs;liver function tests may reveal normal or a mild elevation in bilimbin,ALT and AST,but quite abnormal in serum albumin and prothrombin time in most patients;Coombs-negative hemolytic anemia,normal or markedly subnormal serum alkaline phosphatase (typically ＜ 40 IU/L) are useful for the diagnosis of fulminant WD.In china,KayserFleischer rings are present in 72.2％ of patients at the time of diagnosis,the positive rate is significantly higher in patients with a neurological presentation (93.4％) than patients presenting with liver disease (63.3％),however,they are usually absent in children under 6 years old,occasionly present in patients with chronic cholestatic liver disease.The mean serum ceruloplamin level in WD patients is 71.1 ± 48.7 mg/L,the level is ＜ 200 mg/L in 98.9％ of patients,＜ 100 mg/L in about three fourths patients,＜ 50 mg/L in about half patients,but it may be low in 50％ of patients with severe end-stage liver disease of any etiology too,and even lower than 50 mg/L in patients with nephritic syndrome.Basal 24-hour urinary copper excretion may be ≥ 100 g at presentation in 86.7％ of patients with WD,but also in 22％ of Patients with certain chronic liver diseases,the sensitivity of penicillamine challenge test is lower than basal urinary copper excretion,however,the specificity is significantly higher than former (97％ versus 78％).Hepatic copper determination remains the gold standard for the diagnosis of WD.We have designed a standard method for hepatic copper determination.The most useful cut-off value is 209 g/g dry wt using our method,with the sensitivity of 99.4％,and specificity of 96.1％.However,long-standing hepatic failure and or obstruction can cause heptic copper elevations into the WD area.In recent years,direct complete DNA sequencing has become easy,rapid,less expensive and commercially available.Currently reported mutation detection rate is 90％,the specificity is almost 100％.The limitation to the method has been the ability to identify all the affected alleles in suspected individuals.If no mutation is identified,the diagnosis of WD could not be excluded.None of the laboratory parameters alone allows a definite diagnosis of WD.The WD diagnostic scoring system based on a composite of key parameters helps clinicians to gauge the degree of certainty of the diagnosis:WD scores greater than 4,the diagnosis of WD is highly likely;score 0 or 1,the diagnosis is unlikely.However,the WD diagnosis could not be excluded in suspected patients who do not perform genetic test and hepatic copper determination.Patients with chronic cholestatic liver disease may have scores more than 4.