83例肝豆状核变性患者的临床特征分析

纪雷; 张莹; 孔丽; 赵素贤; 崔坡; 张庆山; 孔令波; 任伟光

doi:10.3969/j.issn.1001-5256.2022.08.023

83例肝豆状核变性患者的临床特征分析

DOI: 10.3969/j.issn.1001-5256.2022.08.023

河北医科大学第三医院中西医结合肝病科，石家庄 050051

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作者贡献声明：孔丽对提出研究思路、设计研究方案有关键贡献并负责文章最后修订；纪雷负责采集、分析数据并负责文章起草及修正。

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孔丽，kongliyouxiang@sina.com

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出版历程
- 收稿日期: 2022-01-12
- 录用日期: 2022-02-28
- 出版日期: 2022-08-20

Clinical features of Wilson's disease: An analysis of 83 cases

Department of Traditional and Western Medical Hepatology, The Third Hospital of Hebei Medical University, Shijiazhuang 050051, China

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Corresponding author: KONG Li, kongliyouxiang@sina.com(ORCID: 0000-0002-8179-8100)

摘要

摘要: 目的总结肝豆状核变性患者的临床特征。方法回顾性分析2013年4月—2021年8月河北医科大学第三医院收治的83例肝豆状核变性患者的临床表现、实验室/影像学/肝组织病理学检查、ATP7B基因检测结果。根据损伤部位不同区分临床类型。多组间比较采用单因素方差分析。结果 83例WD患者中，男女比例1∶ 1.075；发病年龄最小为3岁，平均(21.16±14.87)岁，其中≤18岁者39例(46.99%)；以肝损伤为首发表现者(肝型)为主(63.86%)，31例(37.35%)患者就诊时已进展为肝硬化，5例(6.2%)患者以急性或慢加急性肝衰竭就诊。角膜K-F环阳性62例(74.69%)，其中肝型患者K-F环阳性率为66.04%；血铜蓝蛋白下降79例(95.18%)，24 h尿铜升高73例(87.95%)。25例肝组织病理结果显示，肝组织均有不同程度的炎症、纤维化及脂变，以及铜颗粒沉积。25例ATP7B基因检测结果中，突变位点以外显子8的c.2333G＞T/p.R778L最为常见。结论肝豆状核变性患者以肝病表现为主，角膜K-F环、血清铜蓝蛋白、24 h尿铜指标均有一定局限性。诊断不明时，应行肝组织病理学检查和ATP7B基因检测联合分析。
- 肝豆状核变性 /
- 疾病特征 /
- 诊断, 鉴别
Abstract: Objective To summarize the clinical features of patients with Wilson's disease (WD). Methods A retrospective analysis was performed for the clinical data of 83 patients with WD who were admitted to The Third Hospital of Hebei Medical University from April 2013 to August 2021, including clinical manifestations, Imaging examinations, laboratory examinations, liver histopathological examinations, and ATP7B gene testing results. The patients were divided into groups based on different clinical types. A one-way analysis of variance was used for comparison between groups. Results The youngest age was 3 years for the 83 patients with WD, among whom 39 (46.99%) had an age of ≤18 years, with a mean age of 21.16±14.87 years for all 83 patients. Of all patients, 63.86% had liver-type WD, 31 patients (37.35%) had developed liver cirrhosis at the time of consultation, and 5 patients (6.2%) attended the hospital due to acute or acute-on-chronic liver failure. Of all patients, 62(74.69%) were positive for corneal K-F ring, and the positive rate of K-F ring was 66.04% in the patients with liver-type WD. Among the 83 patients, 79(95.18%) had a reduction in blood ceruloplasmin, and 73(87.95%) had an increase in 24-hour urine copper. The liver histopathological results of 25 patients showed varying degrees of inflammation, fibrosis, steatosis, and copper particle deposition in liver tissue. The ATP7B gene testing results of 25 patients showed that c.2333G > T/p.R778L of exon 8 was the most common mutation site. Conclusion Most patients with WD have the manifestation of liver diseases, and the examinations of corneal K-F ring, serum ceruloplasmin, and 24-h urine copper have their own limitations. Liver pathology and ATP7B gene testing can be performed when it is unable to make a confirmed diagnosis.
- Hepatolenticular Degeneration /
- Disease Attributes /
- Diagnosis, Differential

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表 1 不同临床类型WD患者发病年龄的特点

Table 1. Age characteristics of different clinical types of Wilson's disease

指标	肝型(n=53)	脑型(n=6)	混合型(n=18)	其他型(n=6)
平均发病年龄(岁)	24.60±15.86	36.75±14.95	29.94±12.60	23.43±17.19
发病年龄范围(岁)	3~63	12~61	7~41	3~47
发病年龄段[例(%)]
≤18岁	26(49.06)	2(33.33)	8(44.44)	3(50)
＞18岁	27(50.94)	4(66.67)	10(55.56)	3(50)

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表 2 不同临床类型WD患者铜代谢及角膜K-F环特征

Table 2. Characteristics of copper metabolism and corneal K-F ring in different clinical types of Wilson' s disease

指标	总体(n=83)	肝型(n=53)	脑型(n=6)	混合型(n=18)	其他(n=6)
血清铜蓝蛋白(g/L)	0.09±0.10	0.10±0.12	0.05±0.05	0.07±0.04	0.09±0.07
血清铜蓝蛋白浓度分级[例(%)]
＜0.1 g/L	62(74.70)	37(69.81)	5(83.33)	16(88.89)	4(66.67)
0.1~0.21 g/L	17(20.48)	12(22.64)	1(16.67)	2(11.11)	2(33.33)
≥0.22 g/L	4(7.55)	4(7.55)	0	0	0
24 h尿铜(μmol/24 h)	11.03±12.49	9.89±12.87	6.04±3.88	14.42±13.31	15.85±10.34
K-F环阳性[例(%)]	62(74.69)	35(66.04)	6(100)	15(83.33)	6(100)
注：血清铜蓝蛋白正常值范围为0.22~0.58 g/L；24 h尿铜正常值范围为＜0.47 μmol/24 h。

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