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CC BY 4.0 · Arq Neuropsiquiatr 2024; 82(05): s00441786855
DOI: 10.1055/s-0044-1786855
Original Article

Wilson disease: the diagnostic challenge and treatment outcomes in a series of 262 cases

Doença de Wilson: o desafio diagnóstico e resultados do tratamento em uma série de 262 casos
Marta Mitiko Deguti 
1   Universidade de São Paulo, Faculdade de Medicina, Departamento de Gastroenterologia, São Paulo SP, Brazil.
2   Universidade de São Paulo, Faculdade de Medicina, Instituto de Medicina Tropical, Laboratório de Gastroenterologia e Hepatologia, São Paulo SP, Brazil.
,
Fabiana Cordeiro Araujo 
1   Universidade de São Paulo, Faculdade de Medicina, Departamento de Gastroenterologia, São Paulo SP, Brazil.
,
Débora Raquel Benedita Terrabuio 
1   Universidade de São Paulo, Faculdade de Medicina, Departamento de Gastroenterologia, São Paulo SP, Brazil.
,
Thiago Ferreira Araujo 
2   Universidade de São Paulo, Faculdade de Medicina, Instituto de Medicina Tropical, Laboratório de Gastroenterologia e Hepatologia, São Paulo SP, Brazil.
,
Egberto Reis Barbosa 
3   Universidade de São Paulo, Faculdade de Medicina, Departamento de Neurologia, São Paulo SP, Brazil.
,
Gilda Porta 
4   Universidade de São Paulo, Faculdade de Medicina, Departamento de Pediatria, São Paulo SP, Brazil.
,
Eduardo Luiz Rachid Cançado 
1   Universidade de São Paulo, Faculdade de Medicina, Departamento de Gastroenterologia, São Paulo SP, Brazil.
2   Universidade de São Paulo, Faculdade de Medicina, Instituto de Medicina Tropical, Laboratório de Gastroenterologia e Hepatologia, São Paulo SP, Brazil.
› Institutsangaben Support Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) 06/00499-1.
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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.

Resumo

Antecedentes A doença de Wilson (DW) é um distúrbio autossômico recessivo caracterizado por acúmulo de cobre lesivo aos órgãos. O diagnóstico precoce é dificultado pela raridade e diversidade de apresentações.

Objetivo Descrever características ao diagnóstico e resposta ao tratamento em uma coorte de DW.

Métodos Análise retrospectiva de 262 casos de DW quanto à apresentação clínica, exames complementares, genotipagem e resposta ao tratamento.

Resultados Os sintomas surgiram em uma média aos 17,4 (7–49) anos, e os pacientes foram acompanhados por uma média de 9,6 (0–45) anos. Os pacientes apresentaram principalmente formas hepáticas (36,3%), neurológicas (34,7%) e neuropsiquiátricas (8,3%). Outras apresentações foram hematológicas, renais e musculoesqueléticas. Apenas 16,8% eram assintomáticos. Anéis de Kayser-Fleischer ocorreram em 78,3% dos pacientes, hipoceruloplasminemia em 98,3%, e cuprúria elevada/24h em 73,0%, com aumento após D-penicilamina em 54,0%. Mutações do gene ATP7B foram detectadas em 84,4% dos alelos pesquisados. A ressonância magnética cerebral mostrou alterações em gânglios da base em 77,7% dos pacientes. O tratamento com D-penicilamina foi a escolha inicial em 93,6% dos 245 casos e foi trocado em 21,1% devido a efeitos adversos. Terapias de segunda linha foram zinco e trientina. A resposta terapêutica não diferiu significativamente entre os medicamentos (p = 0,2). Nove pacientes receberam transplante hepático e 82 faleceram.

Conclusão O diagnóstico da DW ainda ocorre em estágios tardios, e as opções terapêuticas são limitadas. A DW deve ser considerada precocemente no diagnóstico diferencial de pessoas com menos de 40 anos com manifestações compatíveis. É necessário incorporar na prática clínica a genotipagem do ATP7B e alternativas terapêuticas à penicilamina.

Keywords

Hepatolenticular Degeneration - Copper-Transporting ATPases - Movement Disorders - Penicillamine - Liver Cirrhosis

Palavras-chave

Degeneração Hepatolenticular - ATPases Transportadoras de Cobre - Transtornos dos Movimentos - Penicilamina - Cirrose Hepática

Authors' Contributions

MMD: conceptualization, data curation, funding acquisition, investigation, methodology, resources, writing – original draft, review, and editing; FCA: conceptualization, data curation, formal analysis, investigation, methodology, and writing – original draft; DRBT: data curation, investigation, and visualization; TFA: data curation and formal analysis; GP: conceptualization, data curation, formal analysis, and investigation visualization; ERB: conceptualization, data curation, formal analysis, investigation, methodology, supervision, and visualization; ELRC: conceptualization, data curation, formal analysis, investigation, methodology, project administration, resources, supervision, visualization, and writing – review & editing.




Publikationsverlauf

Eingereicht: 26. November 2023

Angenommen: 10. März 2024

Artikel online veröffentlicht:
29. Mai 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/)

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Bibliographical Record
Marta Mitiko Deguti, Fabiana Cordeiro Araujo, Débora Raquel Benedita Terrabuio, Thiago Ferreira Araujo, Egberto Reis Barbosa, Gilda Porta, Eduardo Luiz Rachid Cançado. Wilson disease: the diagnostic challenge and treatment outcomes in a series of 262 cases. Arq Neuropsiquiatr 2024; 82: s00441786855.
DOI: 10.1055/s-0044-1786855
 

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