Role for Biochemical Assays and Kayser-Fleischer Rings in Diagnosis of Wilson's Disease
Role for Biochemical Assays and Kayser-Fleischer Rings in Diagnosis of Wilson's Disease
复制标题
生化测定和 Kayser-Fleischer 环在威尔逊病诊断中的作用
DOI：
10.1016/j.cgh.2020.05.044
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发表时间：
2021-03-01
影响因子：
12.6
通讯作者：
Wu, Zhi-Ying
中科院分区：
文献类型：
--
作者：
Dong, Yi;Wang, Rou-Min;Wu, Zhi-Ying
背景与目的：Wilson病是一种常染色体隐性遗传疾病，它损害铜稳态，由编码铜转运P型ATP酶的ATP 7 B的纯合或复合杂合突变引起。患者有不同的临床表现和实验室检查结果，导致诊断困境。我们的目的是从一个超过15年的大型队列中确定与威尔逊病症状和特征相关的因素。我们收集了715名患者的数据（529例有症状，146例无症状，40例未分类）和Wilson病的遗传学确认（平均诊断年龄，18.84岁），从2004年至2019年从中国3家医院招募。我们分析了临床数据沿着血清铜蓝蛋白水平（来自636例患者）、24小时尿铜排泄（收集自131例患者）、Kayser-Fleurring环（眼内铜蓄积，神经系统数据来自355例患者）和磁共振成像（MRI）异常。各组之间的差异进行了分析，采用单因素方差分析，其次是Tukey多重比较test.ESULTS：529例患者的症状，121肝脏功能，355神经功能，28骨肌功能（过早骨关节炎，骨骼畸形，病理性骨折），25精神症状。有肝脏（16.94 +/- 1.03岁; P = 0.0105）或骨肌病变（13 +/- 1.33岁; P = 0.0001）的患者的发病年龄明显小于有神经病变（19.48 +/- 0.46岁）的患者。血清铜蓝蛋白水平在Wilson病的无症状患者和具有骨肌或神经症状的患者中不同。血清铜蓝蛋白水平范围为18.93 mg/L至约120.00 mg/L（分位数为0.025至约0.975）。131例患者中有51例（39%）的尿铜排泄水平低于100 μ g/24小时; 14岁以上患者与14岁或以下患者之间的尿铜排泄水平存在显著差异。在355例患者的神经功能，244例（69%）有异常的结果，从MRI和Kayser-Fleurings. Conclusions脑MRI异常的结果，只有1例患者是阴性的Kayser-Fleurings.Conclusions：血清铜蓝蛋白水平，24小时尿铜排泄量，和Kayser-Fleurings. Conclusions的结果可以用来确定患者谁可能有威尔逊病。血清铜蓝蛋白水平低于120 mg/L的患者和尿铜排泄量高于40 μ g的儿童应进行Wilson病的基因检测。有运动障碍和脑MRI异常但没有Kayser-Fleurring环的患者不太可能患有Wilson病。
BACKGROUND & AIMS: Wilson disease is an autosomal recessive disorder that impairs copper homeostasis and is caused by homozygous or compound heterozygous mutations in ATP7B, which encodes a copper-transporting P-type ATPase. Patients have variable clinical manifestations and laboratory test results, resulting in diagnostic dilemmas. We aimed to identify factors associated with symptoms and features of Wilson disease from a large cohort, over 15 years.METHODS: We collected data from 715 patients (529 with symptoms, 146 without symptoms, and 40 uncategorized) and a genetic confirmation of Wilson's disease (mean age of diagnosis, 18.84 years), recruited from 3 hospitals in China from 2004 through 2019. We analyzed clinical data along with serum levels of ceruloplasmin (available from 636 patients), 24-hr urinary copper excretion (collected from 131 patients), Kayser-Fleisher rings (copper accumulation in eyes, with neurologic data from 355 patients), and magnetic resonance imaging (MRI) abnormalities. Differences among the groups were analyzed using 1-way analysis of variance followed by Tukey multiple comparison test.ESULTS: Of the 529 patients with symptoms, 121 had hepatic features, 355 had neurologic features, 28 had osteomuscular features (premature osteoarthritis, skeletal deformities, and pathological bone fractures), and 25 had psychiatric symptoms. Age of onset was significantly younger in patients with hepatic (16.94 +/- 1.03 years; P = .0105) or osteomuscular features (13 +/- 1.33 years; P = .0001) than patients with neurological features (19.48 +/- 0.46 years). Serum levels of ceruloplasmin differed among asymptomatic patients and patients with osteomuscular or neurologic symptoms of Wilson disease. Serum levels of ceruloplasmin ranged from 18.93 mg/L to approximately 120.00 mg/L (quantiles of 0.025 to approximately 0.975). Fifty-one of 131 patients (39%) had urinary copper excretion levels below 100 mu g/24 hr; there was significant variation in levels of urinary copper excretion between patients older than 14 years vs 14 years or younger. Of the 355 patients with neurologic features, 244 patients (69%) had abnormal findings from MRI and Kayser-Fleisher rings; only 1 patient with abnormal findings from brain MRI was negative for Kayser-Fleisher rings.CONCLUSIONS: Serum level of ceruloplasmin, 24-hour urinary copper excretion, and Kayser-Fleisher rings can be used to identify patients who might have Wilson disease. Patients with serum levels of ceruloplasmin below 120 mg/L and children with urinary copper excretion above 40 mu g should undergo genetic testing for Wilson's disease. Patients with movement disorders and brain MRI abnormalities without Kayser-Fleisher rings are not likely to have Wilson disease.