威尔逊病:262 例系列病例的诊断难题和治疗结果。

IF 1 4区 医学 Q4 NEUROSCIENCES
Arquivos de neuro-psiquiatria Pub Date : 2024-05-01 Epub Date: 2024-05-29 DOI:10.1055/s-0044-1786855
Marta Mitiko Deguti, Fabiana Cordeiro Araujo, Débora Raquel Benedita Terrabuio, Thiago Ferreira Araujo, Egberto Reis Barbosa, Gilda Porta, Eduardo Luiz Rachid Cançado
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引用次数: 0

摘要

背景介绍威尔逊病(WD)是一种常染色体隐性遗传疾病,由于铜超载而导致器官中毒。早期诊断因其罕见性和表现多样性而变得复杂:描述我们的 WD 患者群的诊断特征和对治疗的反应:这是一项回顾性分析,根据临床表现、辅助检查、ATP7B基因分型和治疗反应对262名WD患者进行分层:患者出现症状的平均年龄为 17.4(7-49)岁,平均随访 9.6(0-45)年。患者主要表现为肝病(36.3%)、神经病(34.7%)和神经精神病症(8.3%)。其他表现为血液病、肾病或肌肉骨骼病,16.8%的患者无症状。78.3%的患者出现凯瑟-弗莱舍环(Kayser-Fleischer rings),98.3%的患者出现低球蛋白血症,73.0%的患者出现杯尿/24小时升高,54.0%的患者在服用D-青霉胺后出现杯尿/24小时升高。84.4%的等位基因检测到 ATP7B 基因突变。脑磁共振成像显示,77.7%的患者基底节出现异常。在245名患者中,93.6%的患者首选D-青霉胺,其中21.1%的患者因不良反应而改用其他疗法。二线疗法是锌和三苯氧胺。不同药物的治疗反应没有显著差异(p = 0.2)。9名患者接受了肝移植,82名患者死亡:结论:威尔逊氏病诊断较晚,治疗方案有限。对于年龄在 40 岁以下且有相容表现的患者,WD 可在鉴别诊断中尽早考虑。有必要将 ATP7B 基因分型和治疗方案纳入临床实践。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Wilson disease: the diagnostic challenge and treatment outcomes in a series of 262 cases.

Background:  Wilson disease (WD) is an autosomal recessive disorder that leads to organ toxicity due to copper overload. Early diagnosis is complicated by the rarity and diversity of manifestations.

Objective:  To describe the diagnostic features and response to treatment in our cohort of WD patients.

Methods:  This was a retrospective analysis of 262 WD patients stratified by clinical presentation, complementary exams, ATP7B genotyping, and response to treatment.

Results:  Symptoms occurred at an average age of 17.4 (7-49) years, and patients were followed up for an average of 9.6 (0-45) years. Patients presented mainly with hepatic (36.3%), neurologic (34.7%), and neuropsychiatric (8.3%) forms. Other presentations were hematologic, renal, or musculoskeletal, and 16.8% of the patients were asymptomatic. Kayser-Fleischer rings occurred in 78.3% of the patients, hypoceruloplasminemia in 98.3%, and elevated cupruria/24h in 73.0%, with an increase after D-penicillamine in 54.0%. Mutations of the ATP7B gene were detected in 84.4% of alleles. Brain magnetic resonance imaging showed abnormalities in the basal ganglia in 77.7% of patients. D-penicillamine was the first choice in 93.6% of the 245 patients, and 21.1% of these patients were switched due to adverse effects. The second-line therapies were zinc and trientine. The therapeutic response did not differ significantly between the drugs (p = 0.2). Nine patients underwent liver transplantation and 82 died.

Conclusion:  Wilson disease is diagnosed at a late stage, and therapeutic options are limited. In people under 40 years of age with compatible manifestations, WD could be considered earlier in the differential diagnosis. There is a need to include ATP7B genotyping and therapeutic alternatives in clinical practice.

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来源期刊
Arquivos de neuro-psiquiatria
Arquivos de neuro-psiquiatria 医学-精神病学
CiteScore
2.10
自引率
7.10%
发文量
262
审稿时长
4-8 weeks
期刊介绍: Arquivos de Neuro-Psiquiatria is the official journal of the Brazilian Academy of Neurology. The mission of the journal is to provide neurologists, specialists and researchers in Neurology and related fields with open access to original articles (clinical and translational research), editorials, reviews, historical papers, neuroimages and letters about published manuscripts. It also publishes the consensus and guidelines on Neurology, as well as educational and scientific material from the different scientific departments of the Brazilian Academy of Neurology. The ultimate goals of the journal are to contribute to advance knowledge in the areas of Neurology and Neuroscience, and to provide valuable material for training and continuing education for neurologists and other health professionals working in the area. These goals might contribute to improving care for patients with neurological diseases. We aim to be the best Neuroscience journal in Latin America within the peer review system.
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