Calculated parameters for the diagnosis of Wilson disease

INTRODUCTION@#The diagnosis of Wilson disease (WD) is plagued by biochemical and clinical uncertainties. Thus, calculated parameters have been proposed. This study aimed to: (a) compare the diagnostic values of non-caeruloplasmin copper (NCC), NCC percentage (NCC%), copper-caeruloplasmin ratio (CCR) and adjusted copper in WD; and (b) derive and evaluate a discriminant function in diagnosing WD.@*METHODS@#A total of 213 subjects across all ages who were investigated for WD were recruited. WD was confirmed in 55 patients, and the rest were WD free. Based on serum copper and caeruloplasmin values, NCC, NCC%, CCR and adjusted copper were calculated for each subject. A function was derived using discriminant analysis, and the cut-off value was determined through receiver operating characteristic analysis. Classification accuracy was found by cross-tabulation.@*RESULTS@#Caeruloplasmin, total copper, NCC, NCC%, CCR, adjusted copper and discriminant function were significantly lower in WD compared to non-WD. Discriminant function showed the best diagnostic specificity (99.4%), sensitivity (98.2%) and classification accuracy (99.1%). Caeruloplasmin levels <0.14 g/L showed higher accuracy than the recommended 0.20 g/L cut-off value (97.7% vs. 87.8%). Similarly, molar NCC below the European cut-off of 1.6 umol/L showed higher accuracy than the American cut-off of 3.9 umol/L (80.3% vs. 59.6%) (P < 0.001). NCC%, mass NCC, CCR and adjusted copper showed poorer performances.@*CONCLUSION@#Discriminant function differentiates WD from non-WD with excellent specificity, sensitivity and accuracy. Performance of serum caeruloplasmin <0.14 g/L was better than that of <0.20 g/L. NCC, NCC%, CCR and adjusted copper are not helpful in diagnosing WD.

Enfermedad de Wilson: reporte de caso / Wilson's disease: case report

Antecedentes: La enfermedad de Wilson, también conocida como degeneración hepatolenticular, fue primeramente descrita por el neurólogo británico Kinnier Wilson en 1912. La prevalencia estimada de la enfermedad de Wilson es de 1 caso en 30,000 nacimientos en la mayoría de las poblaciones. Algu- nos estudios sugieren que hombres y mujeres son afectados por igual. Las manifestaciones clínicas de la enfermedad de Wilson son predominantemente hepáticas, neurológicas y psiquiátricas, y algunos pacientes pueden tener una combinación de ellas. Las Guías de Práctica Clínica de enfermedad de Wilson recomiendan penicilamina, trientina, zinc, tetratiomolibdato y dimercaprol como medicamentos. Caso clínico: Se presenta un caso clínico de paciente femenina de 32 años de edad que presentó temblor en miembros superiores, progresivo, bilateral de reposo e intención, que llegó a dificultarle la escritura. Dos meses después la paciente nota trastornos de la marcha, con torpeza, lateropulsión, y posición distónica de pie izquierdo, durante la evolución se agrega hipofonía y disfagia, tanto para só- lidos como líquidos, dificultando pero no impidiendo alimentación, además lentitud mental y trastorno de estado de ánimo. Se le indicó penicilamina y hubo mejoría en su sintomatología en las siguientes consultas. Conclusiones: El pronóstico para los pacientes que tienen buena adherencia al tratamien- to es excelente, incluso en algunos que ya tienen enfermedad hepática avanzada por la enfermedad...(AU)

Estudio molecular del exón 3 del gen atp7b en pacientes cubanos con Enfermedad de Wilson / Molecular genetic analysis of exon 3 of the ATP7B gene in Cuban patients with Wilson's disease

Introducción: La Enfermedad de Wilson es una enfermedad con patrón de herencia autosómico recesivo. Es causada por las mutaciones en el gen atp7b. El exón 3 del gen atp7b es polimórfico y se informan más de 120 polimorfismos en el gen atp7b. Objetivo: Identificar los cambios conformacionales en el exón 3 del gen atp7b y detectar polimorfismos en pacientes cubanos con diagnóstico clínico presuntivo de la enfermedad de Wilson. Materiales y Métodos: Se realizó un estudio descriptivo, en el Centro Nacional de Genética Médica y en el Instituto Nacional de Gastroenterología, durante el período 2007-2013, que incluyó 105 pacientes con diagnóstico clínico presuntivo de la enfermedad de Wilson. La extracción del ADN fue por la técnica de precipitación salina. Se utilizó la técnica de Reacción en Cadena de la Polimerasa para la amplificación del fragmento de interés, y para detectar los cambios conformacionales y la presencia del polimorfismo p.L456V, se usó la técnica de Polimorfismo Conformacional de Simple Cadena, en el exón 3 del gen atp7b. Resultados: En el exón 3 se detectan los cambios conformacionales denominados b y c que correspondieron al polimorfismo p.L456V en estado heterocigótico y homocigótico respectivamente. La frecuencia alélica del polimorfismo p.L456V es de 41 por ciento. Las manifestaciones más frecuentes en los pacientes que presentaron este polimorfismo son las hepáticas. Conclusiones: Se identificó el polimorfismo p.L456V en 64 pacientes cubanos con diagnóstico clínico de la enfermedad de Wilson, lo cual posibilitará hacer estudios moleculares por métodos indirectos(AU)

Introduction: Wilson's disease is a rare inherited autosomal recessive disorder caused by mutations in the ATP7B gene. The exon 3 of the ATP7B gene is polymorphic, and more than 120 polymorphisms of this type have been reported in the literature. Objective: To identify conformational band shifts in exon 3 and detect polymorphisms of the ATP7B gene in Cuban patients, clinically diagnosed with Wilson's disease. Materials and Methods: A descriptive study including 105 patients with the clinical diagnosis of Wilson's disease was conducted at the National Center for Medical Genetics and the National Institute of Gastroenterology from 2007 to 2013. Salting-out protocol was used for DNA extraction. The Polymerase Chain Reaction was used to amplify the fragment of interest and the Single-Strand Conformational Polymorphism was applied in the region of exon 3 of the ATP7B gene to identify conformational changes and the presence of the polymorphism p.L456V. Results: The conformational change called B and C corresponded to the p.L456V polymorphism in the heterozygous and homozygous states, respectively. The allelic frequency of the p.L456V polymorphism in 105 Cuban patients clinically diagnosed with Wilson's disease was 41 percent. The most common manifestations in patients with this polymorphism were related to the liver. Conclusion: The p.L456V polymorphism was identified in 64 Cuban patients with Wilson disease, which will enable us to conduct molecular studies by indirect methods(AU)

Análisis de los polimorfismos p. K832R y p. T991T en pacientes cubanos con diagnóstico clínico de la enfermedad de Wilson / p. K832R and p. T991T polymorphisms’ analysis in Cuban patients with clinical diagnosis of Wilson's disease

Introducción: La Enfermedad de Wilson se caracteriza por la acumulación de cobre en hígado, cerebro, riñones y cornea. Se transmite con un patrón de herencia autosómico recesivo. La causa molecular que la provoca son las mutaciones en el gen ATP7B. Se han informado en la literatura más de 139 polimorfismos en el gen ATP7B. Objetivo: Identificar los cambios conformacionales en los exones 10 y 13 y detectar los polimorfismos p.K832R y p.T991T en el gen ATP7B en pacientes cubanos con diagnóstico clínico de Enfermedad de Wilson. Material y Métodos: Se realizó un estudio descriptivo, durante el período 2012 al 2013, que incluyó 27 pacientes con diagnóstico clínico de Enfermedad de Wilson. Para la amplificación del fragmento de interés, se utilizó la técnica de Reacción en Cadena de la Polimerasa y para identificar los cambios conformacionales se aplicó la técnica de Polimorfismo Conformacional de Simple Cadena, en el exón 10 y 13 del gen ATP7B. La presencia de los polimorfismos p.K832R y p.T991T fueron identificados por secuenciación. Resultados: Se detectaron tres cambios conformacionales diferentes denominados: (a, b y c) en el exón 10 y (a y b) en el exón 13 del gen ATP7B. La frecuencia alélica de los polimorfismos p. K832R y p.T991T en 27 pacientes cubanos con diagnóstico clínico de la Enfermedad de Wilson es 35,2 por ciento y 5,6 por ciento respectivamente. Conclusiones: Se analizó por primera vez en Cuba la combinación de los polimorfismos p. K832R y p. T991T que posibilitará hacer estudios moleculares por métodos indirectos(AU)

Introduction: Wilson's disease is characterized by accumulation of copper in the liver, brain and cornea. It is transmitted with an autosomal recessive inherited disorder. The molecular causes are mutations in the ATP7B gene. It has been reported in the literature more than 139polymorphisms of the ATP7B gene. Objective: Identify the conformational changes in exons 10 and 13 and detect the polymorphisms p.K832R and p.T991T in the ATP7B gene in Cuban patients with clinical diagnosis of Wilson's disease. Material and Methods: Was performed a descriptive study including 27 patients with Wilson’s disease ranging in the time from 2012 to 2013. Were applied the polymerase chain reaction to amplify the fragment of interest and the Conformation Polymorphism Single-Chain procedures in the exon 10 and 13 of the ATP7B gene. The p. K832R and p. T991T polymorphisms were detected by sequencing this fragment. Results: Three different conformational changes were identified: (a, b and c) in exon 10 and (a and b) in exon 13 of the ATP7B gene. The allelic frequency of polymorphisms p. K832R and p. T991T in 27 Cuban patients with clinical diagnosis of Wilson's disease is 35.2 percent and 5.6 percent, respectively. Conclusions: It is the first time in Cuba that a combination of the polymorphisms p. K832R and p. T991T were identified which will allow to make possible molecular studies by indirect methods(AU)

Enfermedad de Wilson rápidamente evolutiva y con presentación inusual / Wilson’s disease with unusual presentation and rapid evolution

Presentamos el caso de un paciente con enfermedad de Wilson que tuvo un comportamiento poco habitual. Previoa la aparición de las manifestaciones neurológicas, tuvo tos como único síntoma, sospechándose una discinesiarespiratoria como forma de presentación. La forma clínica de su enfermedad fue de tipo neurológico puro y sin evidencias de compromiso hepático. No hubo una respuesta satisfactoria al tratamiento instituido y la evolución fue rápida y fatal en poco tiempo.

We present a case of Wilson’s disease with an unusual course. Before the onset of neurological manifestations, cough was the only symptom, suggesting a respiratory dyskinesia as the form of presentation. The disease took a purely neurological type, without signs of hepatic compromise. There was no response to medical treatment, and the evolution was rapid and fatal.

Development of low-density oligonucleotide microarrays for detecting mutations causing wilson’s disease.

Background & objectives: Wilson’s disease (WD) is an autosomal recessive disorder caused by mutations in ATP7B, a copper transporter gene, leading to hepatic and neuropsychiatric manifestations due to copper accumulation. If diagnosed early, WD patients can be managed by medicines reducing morbidity and mortality. Diagnosis of this disease requires a combination of tests and at times is inconclusive due to overlap of the symptoms with other disorders. Genetic testing is the preferred alternative in such cases particularly for individuals with a family history. Use of DNA microarray for detecting mutations in ATP7B gene is gaining popularity because of the advantages it offers in terms of throughput and sensitivity. This study attempts to establish the quality analysis procedures for microarray based diagnosis of Wilson’s disease. Methods: A home-made microarrayer was used to print oligonucleotide based low-density microarrays for addressing 62 mutations causing Wilson’s disease reported from Indian population. Inter- and intra- array comparisons were used to study quality of the arrays. The arrays were validated by using mutant samples generated by site directed mutagenesis. Results: The hybridization reaction were found to be consistent across the surface of a given microarray. Our results have shown that 52 °C post-hybridization wash yields better reproducibility across experiments compared to 42 °C. Our arrays have shown > 80 per cent sensitivity in detecting these 62 mutations. Interpretation & conclusions: The present results demonstrate the design and evaluation of a low-density microarray for the detection of 62 mutations in ATP7B gene, and show that a microarray based approach can be cost-effective for detecting a large number of mutations simultaneously. This study also provides information on some of the important parameters required for microarray based diagnosis of genetic disorders.

Elastosis perforante serpiginosa y pseudo-pseudoxantoma elástico secundarias y tratamiento con D- penicilamina en paciente con enfermedad de Wilson / Elastosis perforans serpiginosa and pseudo-pseudoxanthomaelasticum secondary to D-penicillamine in a patient with Wilson’s disease

La D-penicilamina es la opción terapéutica más utilizada en la enfermedad de Wilson, rara enfermedad genética, autosómica recesiva, en la cual existe una alteración en el metabolismo del cobre que se deposita en los tejidos (hígado, encéfalo y córnea). Presenta numerosos efectos adversos, la mayoría cutáneos, que se observan cuando la droga es utilizada en altas dosis y por largo tiempo; entre ellos se encuentran las dermatosis degenerativas, que incluyen elastosis perforante serpiginosa, cutis laxa, anetodermia y pseudo-pseudoxantoma elástico (también llamado pseudoxantoma elástico símil o pseudoxantoma elástico like). Se presenta una paciente de 29 años con antecedentes de enfermedad de Wilson asociada a elastosis perforante serpiginosa y pseudo-pseudoxantoma elástico, ambas secundarias al tratamiento con D-penicilamina.

Penicillamineis the most commonly used therapeutic option in Wilson's disease.This is a rare, genetic, autosomal recessive diseasein which there is an alteration inthe metabolism of copper that is deposited in the tissues (liver, brain and cornea).It has numerous adverse effects, most of them affecting skin, but they are onlyobserved when the drug is used in high doses and for a long time, such as perforatingelastosis serpiginosa, cutis laxa, anetodermia and pseudo-pseudoxantomaelasticum (also called elasticum pseudoxantoma simil or elasticum pseudoxantomalike). We present the case of a29 year-old woman with a history of Wilson's diseaseand two concomitant degenerative dermatoses: elastosis perforans serpiginosa andpseudo pseudoxanthoma elasticum, both of them, secondary to treatment with Dpenicillamine.

Tratamiento de la enfermedad de Wilson durante el embarazo: primer caso reportado en Cuba / Treatment of Wilson disease during pregnancy. First case reported in Cuba

La enfermedad de Wilson o degeneración hepatolenticular, es un trastorno del metabolismo del cobre que se hereda de forma autosómica recesiva; su incidencia a nivel global es de 1 de cada 30.000 habitantes. Se presenta el primer caso en Cuba de una gestante con diagnóstico de enfermedad de Wilson atendida en la consulta integral para embarazadas del Policlínico Comunitario Docente Sur de Ciego de Ávila; se describe el tratamiento que se debe realizar en estas pacientes.

Wilson disease or hepatolenticular degeneration, is a copper metabolism disorder that is inherited by autosomal recessive form; its incidence at global level is 1 of each 30,000 inhabitants. The first case of a pregnant woman in Cuba with diagnosis of Wilson disease attended in the integral consultation for pregnant women from Community Polyclinic of the south area of Ciego de Avila; the treatment that is due to make in these patients is described.

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: an analysis of 28 Brazilian children

OBJECTIVES: Clinical-laboratory and evolutionary analysis of twenty-eight patients with Wilson's disease. METHODS: Twenty-eight children (twelve females and sixteen males) with Wilson's disease were evaluated retrospectively between 1987 and 2009, with a follow-up of 72 months (1 - 240 months). The clinical, laboratory, and histologic features at diagnosis were recorded at the end of the study. RESULTS: The median age at diagnosis was 11 years (2 - 18 years). Twelve patients were asymptomatic, seven had hepatitis symptoms, five had raised aminotransferase levels, three had hepatomegaly associated with neurological disorders, one had fulminant hepatitis with hemolytic anemia, and six patients presented with a Kayser-Fleischer ring. A histological analysis revealed that six children had chronic hepatitis, seven had cirrhosis, two had steatosis, one had portal fibrosis, and one had massive necrosis. The treatment consisted of D-penicillamine associated with pyridoxine for 26 patients. Adverse effects were observed in the other two patients: one presented with uncontrollable vomiting and the other demonstrated elastosis perforans serpiginosa. At the end of the study, all 26 treated patients were asymptomatic. Twenty-four of the patients were treated with D-penicillamine and pyridoxine, and two were treated with trientine and zinc sulfate. A liver transplant was performed in one patient with fulminant hepatitis, but the final patient died 48 hours after admission to the intensive care unit. CONCLUSIONS: Family screenings associated with early treatment are important in preventing Wilson's disease symptoms and potentially fatal disease progression. The study suggests that Wilson's disease must be ruled out in children older than two years presenting with abnormal levels of hepatic enzymes because of the heterogeneity of symptoms and the encouraging treatment results obtained so far.

Acquired hepatocerebral degeneration and hepatic encephalopathy: correlations and variety of clinical presentations in overt and subclinical liver disease / Degeneração hepatocerebral adquirida e encefalopatia hepática: correlações e variedade de apresentações clínicas na doença hepática evidente e subclínica

Acquired hepatocerebral degeneration (AHD) and hepatolenticular degeneration can have similar clinical presentations, but when a chronic liver disease and atypical motor findings coexist, the distinction between AHD and hepatic encephalopathy (HE) can be even more complicated. We describe three cases of AHD (two having HE) with different neuroimaging findings, distinct hepatic diseases and similar motor presentations, all presenting chronic arterial hypertension and weight loss before the disease manifestations. The diagnosis and physiopathology are commented upon and compared with previous reports. In conclusion, there are many correlations among HE, hepatolenticular degeneration and AHD, but the overlapping of AHD and HE could be more common depending on the clinical knowledge and diagnostic criteria adopted for each condition. Since AHD is not considered a priority that affects the liver transplant list, the prognosis in AHD patients remains poor, and flow interruption in portosystemic shunts must always be taken into account.

A degeneração hepatocerebral adquirida (AHD) e a degeneração hepatolenticular podem ter apresentações clínicas semelhantes, mas quando uma doença hepática crônica e achados motores atípicos coexistem, a distinção entre AHD e encefalopatia hepática (HE) pode ser ainda mais complicada. Descrevemos três casos de AHD (dois tendo HE) com diferentes achados em neuroimagem, doenças hepáticas distintas e apresentações motoras semelhantes, todos com hipertensão arterial e perda de peso antes das manifestações motoras. O diagnóstico e a fisiopatologia são comentados e comparados com relatos prévios. Concluímos que existem muitas correlações entre HE, degeneração hepatolenticular e AHD, mas a sobreposição de HE e AHD pode ser mais comum dependendo do conhecimento clínico e da acurácia dos critérios diagnósticos adotados para cada enfermidade. Como a AHD não é considerada prioridade na lista de transplante hepático, o prognóstico dos pacientes com AHD permanece ruim, e a interrupção do fluxo nos shunts portossistêmicos deve ser sempre considerada.

Doença de Wilson (degeneração hepatolenticular): revisão bibliográfica e relato de caso / Wilson’s disease (hepatolenticular degeneration): revision and case report

Este estudo faz, inicialmente, revisão dos aspectos mais atuais referentes a conceito, quadro clínico, diagnóstico e tratamento do distúrbio metabólico do cobre, definido como doença de Wilson. E relata o caso clínico de um jovem acometido de uma sequência de sintomas superpostos de origem gastrintestinal, neurológico e psiquiátrico. Pela multiplicidade e gravidade dos sintomas, teve o diagnóstico final de transtorno psicótico agudo polimórfico, com intensa inibição psicomotora. A partir de uma análise integrada dos exames já solicitados, suspeitou-se de um distúrbio metabólico de origem hereditária ou adquirida que justificasse simultaneamente os sintomas. O distúrbio da excreção do cobre, doença de Wilson, veio justificar toda a sintomatologia referida e foi confirmado a partir da dosagem sanguínea baixa de ceruloplasmina e da presença dos anéis de Kaiser-Fleischer na córnea do paciente.

It will be initially revised by the authors the most actual aspects of the concept, clinical situation, diagnosis and treatment concerning to a metabolic disturbance of the copper, Wilson?s disease. Afterwards it will be described the clinical case of a young man attacked of a sequence of superposed symptoms of gastrintestinal, neurological and psychiatric origin. For the multiplicity and gravity of the symptoms acute polimórfico with intense psicomotora inhibition had the final diagnosis of "psychotic Upheaval". Starting from an integrated analysis of the exams, it was suspected about a metabolic disturbance of hereditary or acquired origin that justify all the symptoms simultaneously. The disturbance of the excretion of copper, Wilson's disease, came to justify all the referred symptomatology and it was confirmed by the decrease sanguine dosage of ceruloplasmin, the presence of rings of Kayser-Fleischer in the córnea of the patient and of neurological lesion at the magnetic nuclear ressonance. The diagnosis of Wilson's disease in patients with simultaneous digestive (hepática cirrhosis), neurological and inexplicable psychiatric disturbances will always have to be faneed because the precocious treatment will mainly prevent serious and permanent organic damages for the liver and brain. The specific treatment was initiated and the maintenance of exactly has provoked significant improvements and a gradual new outbreak of the symptoms reintegrating the patient the family and the society.

Correlación clínica- para-clínica en un escolar con hipertensión porta de etiología a esclarecer / Clinical-paraclinical in a school with portal hypertension to determine

La hipertensión porta (HTP) es el resultado del incremento de la presión dentro del sistema venoso porta. Se presenta con poca frecuencia en el paciente pediátrico pero es una de las mayores causas de morbilidad y mortalidad en el niño con enfermedad hepática. La mayoría de los pacientes con http presentan un estado hiperdinámico, lo cual aumenta el flujo venoso porta y mantiene la hipertensión. Puede ser secundaria a obstrucción a nivel prehepático, intrahepático o extrahehepático.

Portal hypertension (PH) is the result of increased pressure within the portal venous system. It occurs infrequently in the pediatric patient but it is a major cause of morbidity and mortality in children with liver disease. Most patients with PH have a hyperdynamic state, which increases venous flow and portal hypertension remains. May be secondary to obstruction at prehepatic, intrahepatic or extrahehepatic.

Doença de Wilson em crianças e adolescentes: diagnóstico e tratamento / Wilson's disease in children and adolescents: diagnosis and treatment

OBJETIVO: Descrever as formas de apresentação, as alterações laboratoriais ao diagnóstico e o tratamento de crianças e adolescentes com doença de Wilson. MÉTODOS: Estudo descritivo e retrospectivo de 17 crianças e adolescentes com doença de Wilson atendidos no Ambulatório de Hepatologia Pediátrica do Hospital das Clínicas da Universidade Federal de Minas Gerais no período de 1985 a 2008. Os dados foram coletados dos prontuários e durante as consultas ambulatoriais. RESULTADOS: A idade ao diagnóstico variou de 2,8 a 15,1 anos, com média de 8,8±0,9 anos. A forma de apresentação predominante foi hepática (53 por cento), seguida por assintomáticos provenientes de triagem familiar. O anel de Kayser-Fleischer foi encontrado em 41 por cento dos pacientes. A ceruloplasmina encontrava-se alterada em 15/17 pacientes e o cobre urinário variou de 24 a 1000mcg/24h (mediana: 184mcg/24h). O tratamento instituído foi a D-penicilamina. Observaram-se efeitos colaterais em cinco crianças, sem necessidade de interrupção ou troca da medicação. As respostas clínica e laboratorial, com níveis normais de aminotransferases, foram evidenciadas em 14 pacientes após mediana de 10,7 meses de tratamento. Três crianças morreram (uma por hepatite fulminante e duas com complicações da insuficiência hepática grave), apesar do tratamento. CONCLUSÕES: A doença de Wilson é rara na faixa etária pediátrica. A forma de apresentação predominante é a hepática. Seu diagnóstico se baseia principalmente em dosagem de ceruloplasmina baixa, cobre livre e cobre em urina de 24 horas elevados, mas exige alto grau de suspeição. Apresenta boa resposta e tolerância ao tratamento medicamentoso.

OBJECTIVE: To describe clinical symptoms, laboratory findings at diagnosis and treatment of children and adolescents with Wilson's disease. METHODS: This is a descriptive and retrospective study of a series of 17 children and adolescents with Wilson's disease, assited at the Pediatric Hepatology Ambulatory of the Hospital das Clínicas of Universidade Federal de Minas Gerais, Brazil, from 1985 to 2008. Data were collected by revision of medical charts and during clinical follow-up. RESULTS: Patients were 2.8 to 15.1 years old, with a mean age of 8.8±0.9 years. The disease main presentation was hepatic (53 percent), followed by the asymptomatic form, diagnosed by family screening. The Kayser-Fleischer ring was observed in 41 percent of the patients. The ceruloplasmin was altered in 15 out of 17 patients, and the urinary copper varied from 24 to 1000mcg/24h (median: 184mcg/24h). The treatment was stablished with D-penicillamine in all cases. Slight side effects were observed in five children, with no need to interrupt or change medication. Clinical and laboratory responses to treatment, with normalization of aminotransferases levels, were shown in 14 patients after a median of 10.7 months. Although treated, three patients died (one due to fulminant hepatitis and two due to severe hepatic failure). CONCLUSIONS: Wilson's disease is rare in the pediatric group. In children, the main presentation is the liver disease. The diagnosis can be established by reduced ceruloplasmin levels and elevated copper excretion in the 24-hour urine, but it demands high suspicion level. There are good tolerance and response to medical treatment.