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)

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.

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.

Diagnosis and treatment of scleroderma.

Scleroderma is a rare disease. Approximately 80% of patients are females, and one-half present before the age of 40. Some studies suggest a higher incidence and severity of disease in black females than in whites. Scleroderma affect approximately 20 new patients per million per year and has an estimated prevalence of approximately 250 patients per million in the United States, the synonyms from this disease including Progressive systemic sclerosis (PSS), or diffuse scleroderma. Scleroderma is a multisystem disorder characterized by skin thickening and vascular abnormalities. Causes of scleroderma remain mysterious. Immunologic abnormalities are suggested by the presence of characteristic autoantibodies such as ANA,anticentromere, and anti-Scl-70 antibodies. In addition to skin, the most commonly affected organs are lung and kidney. Three major diseases subsets are recognized based on the extent of skin disease. Limited disease is defined as skin fibrosis in distal extremities and some areas of face and neck. Limited diseases are also known as CREST syndrome. Diffuse disease includes patients with skin abnormalities extending to the proximal extremities (i.e., above the elbow or knee) and trunk. Localized disease manifests as patches (morphea) or bandlike (linear scleroderma) areas of skin thickening.

Effect of monothiol along with antioxidant against mercury-induced oxidative stress in rat.

Efficacy of thiol chelators viz. N-acetyl cysteine and D-penicillamine (NAC and DPA) along with nutritional supplements viz. zinc acetate, sodium selenite and magnesium sulphate (Zn, Se and Mg) in the treatment of mercury intoxication was investigated in rats. This is of particular interest since high bonding affinity between mercuric ion and the thiol group exits. The mutual antagonism of mercury and selenium is one of the strongest examples of the interaction in the trace element field. Adult rats of Sprague-Dawley strain were administered a bolus dose of dimethyl mercury (10 mg/kg) orally. A significant rise in the aspartate aminotransferase, alanine aminotransferase, serum alkaline phosphatase, lactate dehydrogenase, gamma glutamyltranspeptidase, bilirubin and creatinine were observed. Single mercury exposure also resulted in a significant increase in lipid peroxides with a concomitant decrease in reduced glutathione level in liver, kidney and brain. A decrease in the enzymatic activities of acetyl cholinesterase in different regions of the brain was observed. These parameters were restored considerably with chelating agents along with nutritional supplementation, but NAC+Se and DPA+Mg offered significant protection in comparison with other combinations.

Effect of Lead Intoxication and D-Penicillamine Treatment on Hematological Indices in Rats / Efectos de Intoxicación con Plomo y Tratamiento de D-Penicilamina en índices Hematológicos en Ratas

Lead is one of the most important environmental pollution which is toxic to many organ systems. D-penicillamine (D-P) is a chelator drug which is used for treatment of lead toxicity for several years. This study was conducted in order to evaluate the efficacy of D-P in reducing the effects of lead on hematological indices. This study was done on 36 male adult, 6-8 weeks albino Wistar rats in Gorgan University of Medical Sciences. At first male adult rats were exposed to lead acetate in their drinking water. After 8 weeks, 6 rats were selected and blood samples were prepared to assess the effects of lead toxicity. The remained lead exposed rats were divided into recovery and treatment groups where distilled water and D-P was administered for them, respectively. After lead exposure, red blood cell count increased slightly, but hemoglobin and hematocrite were decreased. Also MCV and MCH were significantly decreased (P<0.05). RDW, PDW and MPV were significantly higher in lead exposed rats (P<0.05). After recovery period, most of parameters were close to normal while there were no significant differences between recovery and treatment groups. This study showed that hematologic effects of lead are reversible and D-P administration do not play an important role in subchronic lead intoxication.

El plomo es uno de los más importantes contaminantes ambientales, tóxico para la mayoría de los sistemas orgánicos. La D-penicillamina (D-P) es una droga quelante, la cual se ha usado para el tratamiento de la toxicidad por plomo durante varios años. Este estudio fue dirigido para evaluar la eficacia de la D-P en la reducción de los efectos del plomo en los índices hematológicos. Este estudio se realizó en 36 machos adultos de ratas Wistar albinas de 6-8 semanas, en la Universidad de Ciencias Médicas de Gorgan, Irán. Al inicio, las ratas machos adultas fueron expuestas al acetato de plomo en el agua de beber. Después de 8 semanas, 6 ratas se seleccionaron para evaluar los efectos de la toxicidad del plomo en muestras sanguíneas. Las restantes ratas expuestas fueron divididas para su recuperación, a las cuales se les administró agua destilada y un grupo con tratamiento al que se le suministró D-P. Después de la exposición al plomo, el conteo de glóbulos rojos se incrementó ligeramente, pero la hemoglobina y el hematocrito disminuyeron. También el MCV y el valor de MCH disminuyeron significativamente (P< 0,05). Los valores de RDW, PDW y MPV fueron significativamente altos en las ratas expuestas al plomo (p< 0,05). Luego del periodo de recuperación, la mayoría de los parámetros se acercaron al valor normal y no hubo diferencias significativas entre el grupo recuperado y con tratamiento. Este estudio mostró que los efectos hematológicos del plomo son reversibles y la administración de D-P no juega un rol importante en la intoxicación subcrónica.

A case report on Wilson's disease.

A case of Wilson's disease, a rare autosomal recessive disorder of copper metabolism is reported here. The patient was presented with the difficulty in speech and writing for 4 years and also on walking for 1 year. He also noticed difficulty to perform any work by hands for 6 months. He had splenomegaly and bilateral gynaecomastia. His speech was low volume slurred and monotonous, muscle tone was mildly increased, and gait was limping. Slit lamp examination of eye revealed bilateral Kayser-Fleischer ring with normal visual acuity. Investigations revealed low serum albumin(26 gram/L), increased alanine trans-aminase ( A.L.T=57 U/L). Ultrasonogram of hepatobiliary system revealed coarse hepatic tissue echotexture with splenomegaly. Liver scan showed slightly nonuniform radiotracer distribution in the liver, there was slight increased bony uptake. Serum caeruloplasmin level was 11.51 mg/dl. 24 hours urinary copper excretion was 150 microgram per day. Liver biopsy revealed cirrhotic change. Now he was advised for taking copper chelating agent (penicillamine) in a dose of 1 gram/day.

Pain in abdomen--do not forget lead poisoning.

Lead toxicity has been recognized for thousands of years, and is still around. We encountered 11 patients with lead toxicity in the last two years. All patients had presented with diffuse pain in the abdomen, anemia and mild derangements of liver biochemistry. History of intake of indigenous or herbal medicine for diabetes mellitus or psychosexual disorders was present in eight patients. All of them had elevated blood lead levels. Abdominal pain responded promptly to treatment with chelating agents.

Wilson's disease in Eastern India.

INTRODUCTION: Wilson's disease is an inherited autosomal recessive (AR) disorder of copper metabolism transmitted by a mutant gene on chromosome 13q14-21 and results in abnormal accumulation of copper giving rise to protean manifestations. AIM: The aim is to study the clinical features, biochemical and radiological abnormalities of this disorder in Eastern India and the effect of treatment. RESULTS: Forty nine (n = 49) cases were studied over a period of 10 years. Majority of patients were male with mean age of onset being 11.13 years. They commonly presented with dysarthria, dystonia or drooling. The clinical features were dystonia (96%), silly smile (92%), dysarthria (80%), cognitive decline (71%), tremors (47%), bradykinesia (45%), etc. Family history suggested an autosomal recessive pattern. Sibling screening revealed that 4/8 (50%) were presymptomatic. All but one had presence of Keyser Fleischer (KF) ring in their cornea. Serum copper was reduced in 77% while ceruloplasmin was less in 94% of cases. The commonest abnormality seen in CT/MRI were in basal ganglia (74%) followed by white matter changes (59%) and brain stem changes (20.5%). The response to treatment was not as good and there was an initial deterioration in 50% of cases. Only five patients could go back to their school. CONCLUSION: Wilson's disease have protean manifestations. All children with slowly progressive extrapyramidal syndrome should be investigated for it. Screening of all asymptomatic siblings for Wilson's disease must be carried out. Early institution of proper treatment and life long continuation is indicated in all. In the present series, an earlier age of onset of neurological signs and symptoms were seen; there was initial deterioration in 50% of cases and the response to treatment was not as good.

Diagnóstico de: corea de Sydenham y corea en enfermedad de Wilson / Diagnosis: Sydenham's chorea and chorea in Wilson's disease

Se presentan dos casos en quienes el diagnóstico adecuado permitió tratamiento específico. La corea de Sydenham es usualmente una entidad benigna, pero retardos en el diagnóstico pueden conducir a maniobras terapéuticas inapropiadas. La enfermedad de Wilson puede presentarse como corea, pero esto es raro en nuestro medio. En el caso presentado, el diagnóstico debe considerarse posible ya que no se determinaron niveles de cobre en tejido hepático. La respuesta a tratamiento podrá ayudar en confirmar esta sospecha clínica. Se presenta además una breve revisión de la literatura de éstas y otras entidades relacionadas

Lipogranuloma esclerosante / Sclerosing lipogranuloma

El lipogranuloma esclerosante (LGE) es una afección ocasionada por la inyección en partes blandas de sustancias oleosas de origen conocido o no. Debido a que se trata de una práctica clandestina, su incidencia real se desconoce. Se describen dos casos de LGE en mujeres de 63 y 33 años, que presentan lesiones en mamas, glúteos y muslos. El diagnóstico fue confirmado por los antecedentes y la histopatología

Sclerosing cholangitis: pathogenesis, pathology, and practice

Primary sclerosing cholangitis is a generally progressive, sometimes fatal, chronic hepatobiliary disorder for which no effective medical or surgical therapy now exists. The syndrome occurs most frequently in young men and is characterized by chronic cholestasis, frequent association with CUC, a paucity of serologic markers, hepatic copper overload, and characteristic abnormalities in some liver biopsy specimens and in virtually all cholangiograms. The natural history of the syndrome is still somewhat unclear; the disease likely progresses slowly and relentlessly over a decade or longer from an asymptomatic stage to a condition characterized by symptoms of cholestasis and complicated by cirrhosis and portal hypertension and carcinoma of the bile ducts. Management should first involve a thoughtful decision to observe, which is reasonable in the symptomatic patient with early disease, or to intervene, particularly in patients with symptoms. Therapeutic goals should be defined and should concentrate on either alleviating symptoms, dealing with complications, or attempting to affect the underlying hepatobiliary disease. Symptomatic treatment and therapy for complications is similar to that employed in other chronic liver diseases, but also involves balloon dilatation of dominant strictures in appropriately selected symptomatic patients. Biliary tract reconstructive surgery may alleviate symptoms in selected patients with PSC, but its effect on the natural history of the syndrome has not been determined. Proctocolectomy for CUC in a patient with CUC and PSC does not beneficially affect the progression of the underlying hepatobiliary disease. In contrast, orthotopic liver transplantation may be life-saving for patients with advanced disease. Medical therapy directed at arresting the progression of the underlying hepatobiliary disease is currently experimental and includes cupruretic, immunosuppressive, antifibrogenic, and choleretic agents. Although a single recently completed controlled trial makes it unlikely that cupruretic agents will be helpful in this syndrome, immunosuppressive (i.e. cyclosporin A and methotrexate) and choleretic (i.e. ursodeoxycholic acid) agents alone or in combination are currently undergoing evaluation in randomized trials

Bloqueo cardiaco completo por escleroderma: informe de un caso / Complete heart block due to scleroderma: report of a case

Se presenta el caso de una paciente del sexo femenino de 34 años de edad sin antecedentes familiares ni personales de cardiopatía, hipertensión arterial, tabaquismo o diabetes mellitus. Portadora de escleroderma por tres años, aparentemente estable y bien controlada con D-penicilamina, presentó como primera complicación cardiaca de su enfermedad un cuadro de síncope por bloqueo cardiaco completo con una respuesta ventricular de 30 latidos por minuto. La paciente se recuperó con la inserción de un marcapasos definitivo. Se discute la importancia de la valoración cardiológica en estos pacientes para evitar complicaciones como ésta que puede provocar muerte súbita.

Bloqueo cardiaco completo secundario a intoxicación por cloroquina: informe de dos casos / Secondary complete cardiac block due to chloroquine intoxication: report of two cases

Se presentan dos casos, uno de cuarenta y otro de sesenta y cuatro años de edad con historia de artritis reumatoides seropositiva, quienes después de recibir tratamiento con 150 mg al día de cloroquina durante uno y cinco años respectivamente, desarrollaron bloqueo cardiaco completo que revirtió a ritmo sinusal entre 72 a 96 horas después de que el medicamento fue descontinuado. Dos monitores de Holter de 24 horas al primer y al tercer mes de seguimiento no mostraron alteraciones electrocardiográficas subsecuentes.

Glicosilación no enzimática de proteínas: su rol en las complicaciones crónicas de la diabetes y el envejecimiento / No-enzymatic glycosylation of proteins: role in aging and in the chronic complications of diabetes

En los últimos 15 años la glicosilación no enzimática de las proteínas ha pasado de ser un fenómeno de importancia bromatológica, a tener relevancia en procesos tales como el envejecimiento y las complicaciones crónicas que desarrollan los pacientes diabéticos. El enfoque inicial se centró en los productos de glicosilación temprana de proteínas o productos de Amadori; más recientemente se ha resaltado la formación de los productos de glicosilación avanzada de proteínas como uno de los factores causales de las alteraciones diabéticas y la senilidad. Se han diseñado fármacos que interfieren con las vías de formación de estos productos de glicosilación no enzimática, los cuales tendrían un importante potencial terapéutico en el control de la aparición de las complicaciones crónicas en la diabetes. La determinación en el laboratorio de los productos de glicosilación de proteínas es una herramienta muy útil para el pronóstico de la calidad de vida de un individuo, ya sea normal o diabético, y para el seguimiento del control metabólico a mediano y largo plazo en los pacientes diabéticos