血清铜生化对肝豆状核变性的诊断意义

Diagnosis significance of serum copper biochemical examination in patients with hepato-lenticular degeneration

目的总结肝豆状核变性(HLD)患者的血清铜生化[血清铜离子(Cu2+)、铜氧化酶(SCO)和铜蓝蛋白(CP)]水平,分析其对诊断HLD的价值。方法采用原子吸收光谱法、盐酸对苯二胺比色法和免疫透射比浊法分别测定288例HLD患者和90名正常对照者血清Cu2+、SCO和CP水平;对285例血清铜生化水平降低的患者按临床分型(假性硬化型42例、脑内脏混合型49例、肝型138例、Wilson型59例)和年龄(0～10岁、11～20岁、21～30岁和≥31岁)分组后对其铜生化结果进行比较。结果 288例HLD患者中有3例血清铜生化水平正常,铜生化异常率为98.96%。285例血清铜生化结果降低的HLD患者的血清Cu2+、SCO、CP水平分别为(2.46±1.73)μmol/L、0.027(0.005～0.248)U/L、(55.07±31.87)mg/L,均低于正常对照组[(15.09±2.42)μmol/L、0.492(0.269～0.798)U/L、(306.37±46.84)mg/L](P<0.01)。HLD患者临床分型中Wilson型的SCO水平明显低于肝型及假性硬化型(P<0.01),CP水平明显低于肝型及脑内脏混合型(P<0.05、P<0.01);假性硬化型的血清Cu2+高于其他临床型(P<0.05、P<0.01)。0～10岁组的血清Cu2+最低,≥31岁组血清铜生化结果高于其他年龄组。血清Cu2+、SCO和CP的受试者工作特征(ROC)曲线下面积(AUC)分别为0.995、0.994和0.996;最佳诊断界值分别是6.34μmol/L、0.121 U/L和123.1 mg/L;灵敏度、特异性和误判率均相同,分别为95%、100%和0%。结论血清铜生化检测是诊断HLD最高效、便捷的筛查项目。HLD患者血清铜生化的最佳诊断界值是Cu2+≤6.34μmol/L、SCO≤0.121 U/L和CP≤123.1 mg/L。

Objective To investigate the levels of serum copper biochemical examination [ copper ion （CH2± ） , copper oxidase （SCO） and ceruloplasmin （CP） ] in patients with hepato-lenticular degeneration （ HLD ） and their significance for the diagnosis of HLD. Methods By atomic absorption spectrophotometry, hydrochloric acid-pphenylenediamine color/metric method and immune tnrbidimetric method, 288 patients with HLD and 90 healthy controls were measured for serum Cu2±, SCO and CP levels. The 285 patients with decreasing serum copper biochemical examination levels were classified according to clinical types （42 cases of pseudo-sclerosis type, 49 cases of brain-visceral hybrid type, 138 cases of liver type and 59 cases of Wilson type） and the age（ under 10 years old group, 11 to 20 years old group,21 to 30 years old group and i〉 31 years old group）, and the results of serum copper biochemical examination were compared. Results In the 288 HLD patients, the results of serum copper biochemical examination of 3 cases were normal, and the abnormality rate was 98.96%. In 285 HLD patients with decreasing levels of serum copper biochemical examination, the serum level of Cu2＋ was （ 2.46 ± 1.73 ） μmol/L, the serum level of SCO was 0.027 （0.005-0. 248） U/L, and the level of CP was （55.07 ± 31.87）rag/L, which were significantly lower than those in controls [ （15.09 ±2.42）μmol/L, 0.492 （0.269-0.798） U/L and （306.37 ± 46. 84 ） mg/L ] （P〈0.01）. The SCO level in Wilson type group was significantly lower than those in the liver type and pseudo-sclerosis type groups （P 〈 0.01 ） ,and the CP level was significantly lower than those in the liver type and brain-visceral hybrid type groups （P 〈 0.05 ,P 〈0.01 ）. The serum Cu2＋ level in pseudo-sclerosis type group was higher than those in the other clinical type groups （P 〈 0.05 ,P 〈 0.01 ）. The serum Cu2＋ level was the lowest in under 10 years old group, and the results of serum copper biochemical examination in t〉31 years old group were higher than those in the other age groups. The areas under the receiver operating characteristic （ROC） curve （AUC） were 0. 995, 0. 994 and 0. 996, respectively. The optimal cut-off values were 6.34 μmol/L, 0. 121 U/L and 123.1 rag/L, respectively. The sensitivity, specificity and false identification rate were 95%, 100% and 0%. Conclusions Serum copper biochemical examination is the most convenient screening program for diagnosing HLD. For patients with HLD, the best diagnostic cut-off values are as follows： Cu2＋ ≤6.34 μmol/L,SCO ≤0. 121 U/L and CP ≤123. 1 mg/L.