{"title":"Wilson disease: the diagnostic challenge and treatment outcomes in a series of 262 cases.","authors":"Marta Mitiko Deguti, Fabiana Cordeiro Araujo, Débora Raquel Benedita Terrabuio, Thiago Ferreira Araujo, Egberto Reis Barbosa, Gilda Porta, Eduardo Luiz Rachid Cançado","doi":"10.1055/s-0044-1786855","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong> 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.</p><p><strong>Objective: </strong> To describe the diagnostic features and response to treatment in our cohort of WD patients.</p><p><strong>Methods: </strong> This was a retrospective analysis of 262 WD patients stratified by clinical presentation, complementary exams, <i>ATP7B</i> genotyping, and response to treatment.</p><p><strong>Results: </strong> 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 <i>ATP7B</i> 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 (<i>p</i> = 0.2). Nine patients underwent liver transplantation and 82 died.</p><p><strong>Conclusion: </strong> 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 <i>ATP7B</i> genotyping and therapeutic alternatives in clinical practice.</p>","PeriodicalId":8694,"journal":{"name":"Arquivos de neuro-psiquiatria","volume":"82 5","pages":"1-9"},"PeriodicalIF":1.0000,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Arquivos de neuro-psiquiatria","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1055/s-0044-1786855","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/29 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
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.
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.