Application of a low copper diet guidance based on food exchange portions in children with hepatolenticular degeneration / 中国当代儿科杂志

OBJECTIVES@#To study the efficacy of a low-copper diet guidance based on food exchange portions in children with hepatolenticular degeneration.@*METHODS@#A self-controlled study was conducted from July 2021 to June 2022, including 30 children under the age of 18 who were diagnosed with hepatolenticular degeneration and poorly controlled with a low-copper diet. During the medical visit, personalized low-copper diet guidance was provided to the children and their parents using a copper-containing food exchange table and a copper food exchange chart. During home care, compliance with the low-copper diet of the children was improved by recording dietary diaries and conducting regular follow-ups. The changes in 24-hour urine copper level, liver function indicators, and the low-copper diet knowledge of the children's parents were observed before and after the intervention, with no change in the original drug treatment.@*RESULTS@#After 8, 16, and 24 weeks of intervention, the 24-hour urine copper level decreased significantly compared to before intervention (P<0.05). When compared to 8-week intervention, the urine copper level decreased significantly after 16 and 24 weeks of intervention. The 24-hour urine copper level after 24 weeks of intervention decreased significantly compared to 16 weeks of intervention (P<0.05).After 24 weeks of intervention, the alanine aminotransferase and aspartate aminotransferase levels decreased significantly compared to before intervention (P<0.05). Additionally, in 16 of the cases (53%), alanine aminotransferase and aspartate aminotransferase returned to normal levels. Following 8 weeks of intervention, the low-copper diet knowledge of the children's parents increased significantly (P<0.05).@*CONCLUSIONS@#A low-copper diet guidance based on food exchange portions can effectively decrease the urine copper level and improve liver function in children with hepatolenticular degeneration. Furthermore, it can increase the low-copper diet knowledge of the children's parents.

Guidelines for the diagnosis and treatment of hepatolenticular degeneration (2022 edition) / 中华肝脏病杂志

In order to help liver disease-related clinicians make reasonable decisions for the diagnosis and treatment of hepatolenticular degeneration, the Inherited and Metabolic Liver Disease Cooperative Group of Hepatology Branch of Chinese Medical Association organized relevant field domestic experts in 2021 to jointly compile this guideline based on the clinical and basic research progress.

Interpretation of the 2022 edition guidelines for hepatolenticular degeneration diagnosis and treatment / 中华肝脏病杂志

In order to help liver disease-related clinicians make rational decisions, the Inherited and Metabolic Liver Disease Cooperative Group of Hepatology Branch of Chinese Medical Association released the 2022 edition guidelines for hepatolenticular degeneration diagnosis and treatment. This article introduces the ten highlights of this guideline from the aspects of epidemiology, pathogenesis, clinical characteristics, laboratory tests, diagnosis, treatment, monitoring, and so forth, with practicality and operability as prominent features.

Management of hepatolenticular degeneration during pregnancy / 中华肝脏病杂志

Hepatolenticular degeneration (Wilson's disease, WD) is a kind of autosomal recessive genetic disease characterized by disorders of copper metabolism. It is caused by mutations in the ATP7B gene, resulting in impaired excretion of copper into the bile, and then pathological deposition in the liver, brain, and other organs. Early diagnosis and treatment can significantly improve the prognosis of patients with WD. However, there is still no clear consensus on the treatment and management of WD during pregnancy. Herein, the clinical management of WD during pregnancy is summarized for clinicians' reference.

Degeneración hepatocerebral adquirida reporte de caso y revisión de la literatura / Acquired hepatocerebral degeneration. case report and literature review

Acquired hepatocerebral degeneration also termed acquired hepatolenticular degeneration, cirrhosis-related Parkinsonism o pseudo-Wilson is a rare, progressive and chronic neurological syndrome that occurs in patients with chronic liver disease, particularly in those with surgically or spontaneously induced portosystemic shunts. The clinical features of this pathological entity include extrapyramidal signs, ataxia, cognitive decline and neuropsychiatric changes, such as delirium, apathy, lethargy and emotional instability. Brain Magnetic Resonance Imaging classically shows symmetrical T1-weighted hyperintensities in the globus pallidus, substantia nigra and periaqueductal gray matter. Although its pathogenesis is not completely elucidated, it is postulated that the excess manganese accumulation and deposition in the basal ganglia, leading to dysfunctional dopaminergic system in this anatomical location, would have a key role in triggering the disease. Orthotopic liver transplantation is the mainstay of treatment and is considered effective by reducing motor and cognitive alterations. Other therapeutic alternatives that have reported symptomatic improvement are the use of bromocriptine or levodopa and portosystemic shunts occlusion. In this article, we report a case of a 63-year-old woman with clinical manifestations over the course of one year, characterized by cognitive decline, chorea, gait and language disturbances. She was examined with plasma levels of copper and ceruloplasmin, which excluded the possibility of Wilson´s Disease, its main differential diagnosis. Neuroimaging revealed T1-weighted hyperintensity in the pallidum, confirming suspected diagnosis of acquired hepatocerebral degeneration.

Avaliação fonoaudiológica na doença de Wilson com relato de caso ilustrativo / Phonoaudiological evaluation in Wilson´s disease with illustrativecase report

A doença de Wilson (DW) é uma doença genética, autossômica recessiva, causada por mutações no gene ATP7B que atua na excreção biliar do cobre. A falência desta via provoca alterações no metabolismo do cobre no organismo pelo comprometimento da síntese de ceruloplasmina, provocando a deposição do metal em vários locais do organismo principalmente, fígado, cérebro, córnea e rins. O paciente como consequência pode apresentar manifestações neurológicas, psiquiátricas, hepáticas e de outros sistemas. O presente relato visa mostrar a avaliação fonoaudiológica e descrever a disartria em paciente com DW, que apresentou os primeiros sinais da doença com quadro súbito de catatonia, algia em membros superiores e inferiores, seguidos por alteração da fala, marcha e deglutição.A avaliação fonoaudiológica da articulação constou das cinco bases motoras da fala. Foi utilizado também o exame tempo máximo fonatório (TMF), visando avaliar o fluxo aéreo, a musculatura laríngea, a eficiência glótica e o suporte respiratório para a fala. Utilizou-se também a avaliação e inspeção da musculatura orofacial. Foram detectadas as seguintes alterações nas bases motoras da fala: articulação: alteração da extensão na produção de fonemas; precisão de vogais; extensão da frase; respiração: alteração na coordenação pneumofonoarticulatória; ressonância: nasalidade; fonação: alteração do fluxo aéreo e da musculatura laríngea; comprometimento do suporte respiratório e travamento articulatório; prosódia: alteração na velocidade da leitura de textos, entonação e marcação de prosódica de sílaba tônica.Acredita-se que o processo de terapia para disartria deve ser intensivo, onde se conclui que os benefícios do acompanhamento fonoaudiológico têm relação direta com frequência e o tempo da realização dos mesmos.

Wilson´s disease (DW) is a genetic, recessive autosomal disease, caused by mutations of the ATP7B gene that acts in the biliary excretion ofcopper. The failure of this pathway causes changes of copper metabolism in the organism by impairing the ceruloplasmin synthesis, and leadingto deposition of the metal in various sites of the organism, mainly liver, brain, cornea and kidneys. The patient, as a consequence, can presentneurological, psychiatric, hepatic manifestations, as well as of other systems.The present report aims at showing the phonoaudiological evaluation and to describe the dysartria in a patient with WD who displayed the first signs of the illness with sudden catatonia and pain in the superior and inferior limbs, and changes of speech, gait and swallowing.The phonoaudiological evaluation included the five motor bases of speech. The examination of the maximum phonatory time (MPT) was also used to evaluate the aerial flow, the laryngeal muscle, the glottic efficiency, and the respiratory support of speech. The evaluation of orofacial muscle was also accomplished. The following changes in the motor bases of speech were detected - articulation: extension in the production of phonems, precision of vowels, extension of the phrase; breath: changes in the pneumophonoarticulatory coordination,; resonance: nasality; phonation: changes of the aerial flow and of the laryngeal muscle; respiratory support for speech prosody: changes in the speed of the reading texts, tune and marking of tonic syllable prosody.It is believed that the therapeutic process for dysartria must be intensive, and the benefits of phonoaudiological follow-up bears a direct relation with the frequency and time of its accomplishment.

Wilson's disease in southern Brazil: a 40-year follow-up study

BACKGROUND: Long-term data on the clinical follow-up and the treatment effectiveness of Wilson's disease are limited because of the low disease frequency. This study evaluated a retrospective cohort of Wilson's disease patients from southern Brazil during a 40-year follow-up period. METHODS: Thirty-six Wilson's disease patients, diagnosed from 1971 to 2010, were retrospectively evaluated according to their clinical presentation, epidemiological and social features, response to therapy and outcome. RESULTS: Examining the patients' continental origins showed that 74.5 percent had a European ancestor. The mean age at the initial symptom presentation was 23.3 ± 9.3 years, with a delay of 27.5 ± 41.9 months until definitive diagnosis. At presentation, hepatic symptoms were predominant (38.9 percent), followed by mixed symptoms (hepatic and neuropsychiatric) (30.6 percent) and neuropsychiatric symptoms (25 percent). Kayser-Fleischer rings were identified in 55.6 percent of patients, with a higher frequency among those patients with neuropsychiatric symptoms (77.8 percent). Eighteen patients developed neuropsychiatric features, most commonly cerebellar syndrome. Neuroradiological imaging abnormalities were observed in 72.2 percent of these patients. Chronic liver disease was detected in 68 percent of the patients with hepatic symptoms. 94.2 percent of all the patients were treated with D-penicillamine for a mean time of 129.9 ± 108.3 months. Other treatments included zinc salts, combined therapy and liver transplantation. After initiating therapy, 78.8 percent of the patients had a stable or improved outcome, and the overall survival rate was 90.1 percent. CONCLUSION: This study is the first retrospective description of a population of Wilson's disease patients of mainly European continental origin who live in southern Brazil. Wilson's disease is treatable if correctly diagnosed, and an adequate quality of life can be achieved, resulting in a long overall survival.

Enfermedad de Wilson: revisión del tema / Wilson's disease: a review

La Enfermedad de Wilson es un trastorno autosómico recesivo causado por mutaciones en el genATP7B que producen anormalidad en el metabolismo del cobre, con acumulación de este elementoen distintos órganos y tejidos. El diagnóstico se basa en la combinación del cuadro clínico con diversaspruebas bioquímicas, pues ninguna de ellas, aisladamente, es diagnóstica. En la actualidad se cuentacon un tratamiento efectivo para esta enfermedad, basado en la utilización de quelantes del cobre,para movilizarlo de los sitios donde se acumula y promover su excreción, así como de zinc parabloquear su absorción intestinal. El trasplante hepático es el tratamiento de elección en los pacientescon hepatopatía fulminante, así como en los que llegan a la cirrosis descompensada. En esta revisiónse incluyen aspectos bioquímicos, genéticos, clínicos, diagnósticos y terapéuticos de esta enfermedad.

Wilson’s disease: a reviewWilson’s disease is an autosomal recessive disorder caused by mutations in the ATP7B gene thatlead to an abnormal metabolism of copper, resulting in the accumulation of this element inseveral organs and tissues. Its diagnosis is based on the combination of the clinical picture withvarious biochemical tests, neither one of which is, by itself, diagnostic of the disease. Presentlythere are effective treatments for EW based on the administration of chelating agents to promotemobilization of copper from the accumulation sites and its excretion. Zinc is also used in orderto block the intestinal absorption of copper. Liver transplantation is the treatment of choice inpatients with fulminating hepatitis, as well as in those with decompensated cirrhosis. This reviewincludes the following aspects of Wilson‘s disease: biochemical, genetic, clinical, diagnostic, andtherapeutic.

Doença de Wilson em crianças e adolescentes: como fazer diagnóstico precoce / Wilson's disease in children and adolescent: a key to an early diagnosis

A doença de Wilson é uma desordem autossômica recessiva do metabolismo do cobre, que leva à impregnação desse metal em diversos tecidos como o fígado, cérebro, córnea e rins. Tem prevalência de 1:40.000 e evolui de forma progressiva e fatal se não tratada. Seu diagnóstico depende de suspeição clínica e exames laboratoriais, podendo ser difícil nos pacientes assintomáticos ou com insuficiência hepática grave. A tríade clássica de apresentação é hepática, neurológica e oftalmológica. Na criança, a forma de apresentação mais comum é a hepática (aguda ou crônica). Os critérios diagnósticos são baseados na presença de ceruloplasmina baixa, cobre em urina de 24 horas e cobre livre elevados e avaliação oftalmológica à procura do anel de Kayser-Fleischer. O tratamento medicamentoso deve ser instituído o quanto antes, de forma a evitaremse as lesões teciduais do excesso de cobre, daí a grande importância do diagnóstico precoce. A droga de escolha é a D-penicilamina, mas é necessário o monitoramento de seus possíveis efeitos colaterais e eventuais pioras do quadro neuropsiquiátrico. Existem outras drogas, como a trientina, tetratiomolibdato e o zinco, que também têm efeito na redução do cobre orgânico. (AU)

Wilson disease is an authossomal recessive disorder of copper metabolism that leads to the impregnation of the metal in different tissues such as the liver, brain, cornea and kidneys. There is a prevalence of 1:40,000 and evolution is progressive and fatal if untreated. The diagnosis depends on clinical suspicion and laboratory tests, and may be difficult in situations such as the asymptomatic patients or with severe liver insufficiency. The classic triad presentation is the hepatic, neurological and ophthalmologic disease. In children, the most common is the hepatic (acute or chronic). The diagnosis criteria are based on the presence of low ceruloplasmine, elevated copper in 24-hour urine and high seric copper and ophthalmologic evaluation in search of Kayser Fleischer ring. The medication treatment must be established as soon as possible so as to prevent tissue lesions due to copper excess, hence the great importance of early diagnosis. The drug choice is the D-penicilamin, with careful monitoring of side effects and attention for occasional worsening of the neuropsychiatric state. There are other drugs as trientine, tetratiomolibdato and zinc that also have an effect on the reduction of organic copper. (AU)

Doença de Wilson: apresentação clínica, diagnóstico e tratamento / Wilson's disease: clinical presentation, diagnosis and treatment

A doença de Wilson é um erro inato do metabolismo do cobre causado por uma mutação no gene ATP7B, responsável por seu transporte. É uma doença de herança autossômica recessiva, caracterizada pela deposição excessiva de cobre principalmente no fígado e no cérebro. Clinicamente, os pacientes apresentam manifestações hepáticas, neurológicas e psiquiátricas. O diagnóstico pode ser feito quando as seguintes características estiverem presentes: anéis de Kayser-Fleischer na córnea, diminuição dos níveis plasmáticos de ceruloplasmina e sintomas neurológicos típicos. A prevenção de danos permanentemente severos depende do reconhecimento e diagnóstico precoces pelo médico, seguidos de tratamento apropriado. A doença de Wilson pode ter prognóstico excelente, desqe que o tratamento seja feito durante toda a vida.

Wilson's disease is an inborn error of copper metabolismo caused by a mutation to the cooper-transporting gene ATP7B. This disease has an autosomal recessive mode of inheritance, and is characterized by excessive cooper deposition, predominantly in the liver and brain. Clinically, patients usually present hepatic, neurologic or psychiatric manifestations. The diagnosis can be done when these symptoms are present: Kayser-Fleischer rings, low serum ceruloplasmin levels and typical neurological symptoms. The prevention of severe permanente damage depends upon early recognition and diagnosis by the physician, followed by appropriate anticopper treatment. Wilson's disease it can have an excellent prognosis since that treatment either for all the life.

Wilson's Disease: a case report and a historical review / Doença de Wilson: relato de caso e revisão histórica

The purpose of this report is to present a short review of the history of Wilson’s disease and to describe the first diagnosed case at the Neurologic Clinic of Hospital das Clínicas of São Paulo University Medical School. The topics of the historical review are the first contributions of authors along the second half of the XIX century, the seminal monograph of Samuel Alexander Kinnier Wilson (1912), the landmarks in the investigation of mechanisms of the disease and the introduction of the first effective treatment by John Walshe (1956). The first case studied in our Clinic, in 1946, was a 20 year-old male whose main neurological manifestations were postural tremor (“wing beat”) and dysarthria and could be characterized as Westphal-Strümpell form of the disease. Along the discussion of this case difficulties to establish the diagnosis and to treat the patient at that time are highlighted. We conclude with a brief history of the development of researches on Wilson’s disease in our Clinic, with an honor to the pioneer contributions of Horácio Martins Canelas.

Neste artigo inicialmente é feito um retrospecto dos principais marcos na história dos conhecimentos sobre a doença de Wilson, desde as primeiras descrições de casos no século XIX, passando pela magnífica monografia de Samuel Alexander Kinnier Wilson, m 1912, pelas descobertas sobre a causa da doença e chegando à era do tratamento efetivo da moléstia inaugurada por Walshe em 1956. A seguir, relata-se o primeiro caso de doença de Wilson estudado na Clínica Neurológica do HC-FMUSP. O paciente admitido na Clínica Neurológica em 1946, aos 20 anos de idade, apresentava a variante da doença em que predominavam tremor postural e disartria, conhecida como forma de Westphal-Strümpell. Na discussão, são ressaltadas as dificuldades da época para a confirmação do diagnóstico e para o tratamento; além de se realizar um breve histórico do estudo da doença na Clínica Neurológica, com o devido realce para a figura de Horácio Martins Canelas, pela sua participação pioneira nas pesquisas sobre a doença de Wilson em nosso meio.

Enfermedad de Wilson / Wilson's disease

La enfermedad de Wilson (EW) es un trastorno autosómico recesivo, que produce una acumulación anormal de cobre y afecta principalmente el hígado y los ganglios básales del cerebro, por lo que también es llamada degeneración hepatolenticular, y debe sospecharse en menores de 40 años con encefalopatía asociada a signos o síntomas de hepatopatía. Se reporta el caso de un paciente de 38 años, varón, con cuadro de cirrosis e hipertensión portal, sin antecedentes personales ni familiares de importancia a quien se le diagnosticó EW. Se revisa el tema, la fisiopatología, la clínica y la tendencia terapéutica actual. Aunque es una entidad rara, la EW debe sospecharse ya que de no contar con un diagnóstico oportuno, el pronóstico y la calidad de vida del paciente se ensombrece, y la progresión hacia falla hepática fulminante y muerte es inevitable.

Doença de Wilson: relato de caso / Wilson's disease: a case report

A doença de Wilson é um erro inato do metabolismo do cobre, com manifestaçöes neurológicas e hepáticas. Reporta-se o caso de um homem de 42 anos de idade com doença de Wilson e apresentaçäo atípica de tubulopatia renal.(au)

Doença de Wilson ("forma hepática") em regiäo endêmica para esquistossomose mansoni: apresentaçäo clínica de 25 pacientes / Wilson's disease (\"hepatic form\") in a region endemic for mansoni schistosomiasis: the clinical presentation of 25 patients

No Brasil, com populaçao jovem e regioes onde a esquistossomose mansoni é endêmica, a doença de Wilson pode nao ser diagnosticada em pacientes erroneamente rotulados como portadores de esquistossomose hepatoesplênica ou hepatointestinal. Vinte e cinco portadores de doenças de Wilson com hepatopatia (14 homens e 11 mulheres) foram investigados em Belo Horizonte; a média de idade foi 13,7 anos (3 a 22). Dezenove tinham hepatomegalia (76 por cento) e nove esplenomegalia (36 por cento). Vinte e dois (88 por cento) tinham cirrose. O anel de Kaiser-Fleisher foi detectado em 15 (60 por cento). Quatro (16 por cento) tinham evidentes distúrbios neurológicos. Onze (44 por cento) tinham ascite e igual número, icterícia variável. Noventa e um vírgula três por cento e 92 por cento tinham níveis séricos de ceruloplasmina e cobre, respectivamente, diminuídos. Oitenta e quatro vírgula dois por cento tinham excreçao urinária de cobre em 24 horas aumentada; nos sete em quem foi dosado o cobre hepático, os valores estavam elevados. Seis de nove tinham excreçao de cobre urinário após 24 horas de uso de penicilina ("teste da penicilamina") aumentada em pelo menos 10 vezes. Três dentre 19 pacientes (15,8 por cento) tinham ovos de Schistosoma mansoni nas fezes, prevalência comum na populaçao. Suas biopsias mostravam cirrose inativa, sem alteraçoes de esquistossomose mansoni. Quatorze dos pacientes (56 por cento) poderiam ser erroneamente diagnosticados como portadores de esquistossomose hepatointestinal ou hepatoesplênica, tendo, na verdade, doença de Wilson associada ou nao a esquistossomose intestinal assintomática e, portanto, perdendo a chance de um tratamento precoce. O acompanhamento de 22 pacientes foi de 52 meses (1 a 96). Oito (36,3 por cento) faleceram, quatro por hemorragia digestiva alta, três por insuficiência hepática terminal e um com insuficiência hepática fulminante. A maioria, incluindo os falecidos, abandonou o uso da penicilamina ou a usava de modo irregular, sobretudo pelo custo elevado. Um paciente de 17 anos foi submetido com sucesso a transplante de fígado em 1989.

Enfermedad de Wilson: Experiencia clínica y revisión del tema

La enfermedad de Wilson es una enfermedad en la cual excesivas cantidades de cobre se acumulan en el cuerpo; inicialmente en el hígado y luego en otros órganos como el cerebro y ojo. la forma más común de la enfermedad se presenta insidiosamente, con laxitud, fatiga y anorexia, progresando crónicamente hacia la hipertensión portal, ascitis y falla hepática. El diagnonóstico de la enfermedad se hace mediante la presencia del anillo Kayser-Fleischer y el hallazgo de una concentración de ceruplasmina sérica menor 20 mg por ml. Cuando existe dificultad en el diagnóstico, la concentración de cobre hepático o la incorporación de cobre radioactivo, hacen el diagnóstico. La concentración tóxica de cobre en el cuerpo puede ser removida y prevenida su acumulación, utilizando D-penicilamina, tetramina o Zinc. En algunos casos el tratamiento quirúrgico, decompresión o transplante, se reserva para cierto tipo de pacientes. Presentamos una completa y actualizada revisión del tema, así como parte de nuestra experiencia clínica en el Hospital San Juan de Dios

Fulminant Wilson's disease: a report

A 21 y/o female presented with fulminante hepatic failure and hemolysis. On the basis of the clinical presentation, levels of ceruloplasmin and serum copper a presumptive diagnosis of Wilson's disease was made. In spite of upportive measures and hemodialysis, the patient died one week after admission. Postmortem examination showed cirrhosis and increased cooper stores in the liver, corroborating the clinical diagnosis of Wilson's disease. Study of the four siblings revealed that two are carriers, one is healthy and one may have the disease. Wilson's disease in a rare cause of fulminant hepatic failure that must be suspected specially when hemolysis is associated to the clinical picture. This mode of presentation is virtually fatal and early liver transplantation is the best form of therapy