Analysis of clinical and biochemical spectrum of Wilson Disease patients.

Background and Aims: Wilson disease (WD) is autosomal recessive disorder of copper metabolism. Wilson disease patients usually suffer from hepatic or neuropsychiatric complications. The symptoms appear between ages five to 35 but it can vary from two years to 72 years. Materials and Methods : Study was carried out from June 2008 to November 2010. This study included nine families with eleven cases of WD to determine clinical presentation, diagnostic findings (including laboratory results) and liver histology. It included 11 patients who presented with hepatic manifestations and/or Neuropsychiatric manifestations and/or family history suggesting features of WD. Patients with hepatitis B and C and those with history of taking antipsychotic drugs were excluded from the study. Patient's data was included in a well designed performa. Liver function test, serum ceruloplasmin, serum copper, 24 hour urinary copper, blood complete picture were analyzed. Quantitative data such as age, hemoglobin etc were expressed as mean with ± SD and quantitative variables such as sex, movement disorders, hepatic involvement etc were expressed as frequency and percentage. Results: There were five male and six female patients with evidence of various manifestations here (i) hepatic in which they had only liver dysfunction (ii) hepatic and neurological (iii) neurological. The mean age of presentation was 8.7±3.92 years (range 4-19 years) and 45% were male patients. Decreased serum ceruloplasmin, enhanced 24-h urinary copper excretion and signs of chronic liver damage were confirmed in all patients and Kayser-Fleischer rings (KF rings) in 72% of patients. In severe WD patients, serum prothrombin activity was less than 50%, serum ceruloplasmin were low and serum copper levels were high than those in non-severe WD patients. High degree of suspicion leads to early treatment with good outcome. Conclusions: The WD is rare but important cause of chronic liver disease. Clinical and biochemical analysis in cases of patients with unexplained liver disease with high degree of suspicion can lead to early treatment with good outcome.

Atomic absorption spectrometry in Wilson's disease and its comparison with other laboratory tests and paraclinical findings

Wilson's disease [WD] is an autosomal recessive disease with genetic abnormality on chromosome 13 causing defect in copper metabolism and increased copper concentration in liver, central nervous system and other organs, which causes different clinical manifestations. The aim of this study was to determine the sensitivity of different clinical and paraclinical tests for diagnosis of Wilson's disease. Paraffin blocks of liver biopsy from 41 children suspicious of WD were collected. Hepatic copper concentrations were examined with atomic absorption spectrophotometry [Australian GBC, model: PAL 3000]. Fifteen specimens had hepatic copper concentration [dry weight] more than 250 micro g/g. Clinical and laboratory data and histologic slides of liver biopsies of these 15 children were reviewed retrospectively. Liver tissue was examined for staging and grading of hepatic involvement and also stained with rubeonic acid method for copper. Patients were 5-15 years old [mean age=9.3 years, standard deviation=2.6] with slight male predominance [9/15=60%]. Five [33%] patients were 10 years old. Three [20%] of them were referred for icterus, 8 [54%] because of positive family history, 2 [13%] due to abdominal pain and 2 [13%] because of hepatosplenomegaly and ascites. Serum AST and ALT levels were elevated at the time of presentation in all patients. In liver biopsy, histological grade and stage was 0-8 and 0-6 respectively, 2 [13%] had cirrhosis, 1 [7%] had normal biopsy and 12 [80%] showed chronic hepatitis. Hepatic copper concentrations were between 250 and 1595 micro g/g dry weight. The sensitivity of various tests were 85% for serum copper, 83% for serum ceruloplasmin, 53% for urinary copper excretion, 44% for presence of KF ring and 40% for rubeonic acid staining on liver biopsies. None of the tests stated in the article were highly sensitive for diagnosis of WD, so we suggest that diagnosis should be based on combination of family history, physical examination and different tests

Neurological and other manifestations of Wilson disease; 1998-2005

Wilson disease [WD] is an inherited copper metabolism dysfunction disease characterized by cirrhosis and CNS findings. Wilson disease is important because it is fatal not recognized and treated. Our Goa of study is to investigate the clinical signs and symptoms, lab results and other relevant matters in our patients in order to obtain a better understanding of this potentially lethal disease in our country. We have evaluated 21 cases of children with Wilson disease who were referred to Loghman and Imam Hussein Hospital between years 1998-2005. The mean age of our patients was 9 years. The presenting symptom was ascites and extremity edema in 6[28.5%] patients, behavioral changes or neurological signs in 5[24%] simultaneous Ascites and icter in 9[43%] patients and in one patient the presenting manifestation was hemolytic anemia [4.8%]. One of our patients died because of fulminant hepatitis in the course of admission [4.8%]. We showed in this study that Wilson disease can be presented by a manifold symptom in children and adolescence. Having a good concept of these symptoms in high clinical suspicious are required to diagnose this potentially lethal disease at the proper time in order to decrease the potential adverse effects of the disease especially the neuropsychiatric damages significantly

[Evaluating the relation between diabetic nephropathy and urinary copper level]

Diabetes is the most important metabolic disease in human. The prevalence of both types of diabetes is rapidly increasing over the world. Diabetes causes many complications including ESRD. Diabetes is responsible for 30% of ESRD. The prevalence of diabetic nephropathy in Iran is also high. Many of these patients are becoming dialysis dependent. Many studies have shown the changes of trace metals' levels in diabetic patients including cupper, zinc, Manganese and Chromium. This study evaluates the Correlation between urinary cupper and diabetic nephropathy. This is a case-control study. Samples were selected among type 2 diabetic patients attending to diabetes clinic in Vali-e-Asr hospital in Arak. Diabetic patients were divided in two groups based on microalbuminuria, 42 patients in case and 40 patients in control group. Then the patients were classified based on duration of diabetes into 4 groups and based on the HbA1c into two groups. Then urinary cupper was determined with atomic absorption spectophotometry and compared. Independent T test was used to analyze data. The patients were 28.1% male and 69.9% female in case group and 37.5% male and 62.5% female in control group. The mean cupper level was 36.14 micro g/L [14.54-57.74] in case group and 14.77% micro g/L [10.17-19.37] in control group. There was a statistically significant difference between two groups [p=0.003]. The results show a positive relation between urinary cupper and diabetic nephropathy and confirmed the results of other studies that reported the elevation of cupper in microalbuminuria. This study also showed that age, gender, duration of diabetes and HbA1c level have no effect on urinary cupper

Wilson's disease with hepatic presentation in childhood.

Diagnosis of Wilson's disease with hepatic presentation in childhood using clinical and common laboratory parameters is still challenging and is often missed or delayed. The aim of the study was to document the clinical and laboratory parameters of hepatic presentation of Wilson's disease in children. The study was conducted at a tertiary-care hospital in a developing country. Clinical and common laboratory parameters were recorded in 32 Wilson's disease children with hepatic presentation. The diagnosis was based on positive family history, Kayser-Fleischer ring, low serum ceruloplasmin level, elevated basal urinary copper excretion and favorable response to therapy with D-penicillamine. Mean age+/-SD at presentation was 9+/-2.97 years and 21 (65.6%) were boys. Chronic liver disease (21; 65.6%) followed by fulminant hepatic failure 1(6; 18.8%) were the commonest presentation. In the whole group, Kayser-Fleischer ring was found in 21 (65.6%), low serum ceruloplasmin in 16 (50%) and elevated basal urinary copper excretion in all 32 (100%) children. Diagnosis of Wilson's disease was made at presentation on the basis of i) Kayser-Fleischer ring, low serum ceruloplasmin, elevated basal urinary copper excretion and favorable response to D-penicillamine therapy in 11 (34.4%), ii) Kayser-Fleischer ring, elevated basal urinary copper excretion and favorable response to D-penicillamine therapy in 10 (31.2%), iii) elevated basal urinary copper excretion and favorable response to D-penicillamine therapy in 6 (18.8%) and iv) low ceruloplasmin, elevated basal urinary copper excretion and favorable response to D-penicillamine therapy in 5 (15.6%) children. Wilson's disease can not be excluded in children presenting with hepatic involvement using the commonly practiced clinical and laboratory parameters. A combination of various clinical and laboratory parameters were used for the diagnosis of Wilson's disease in the studied children with hepatic presentation.

Wilson's disease: Brain MRI, Tc-99m HMPAO SPECT and clinical correlation

Introduction: Wilson's disease is a genetic disease characterized by excess deposition of copper in the liver, brain, cornea and kidneys. Brain damage leads to several psychiatric and neurological manifestations. However, a little research has been published about the role of anatomo-functional diagnostic modalities in the evaluation of the clinical course of the disease

Aim of the study: to evaluate and compare the role of brain MRI and Technetium-99m hexamethylpropylene-amine oxime [Tc-99m HMPAO] SPECT in assessing brain involvement in Wilson's disease and correlating these findings with the clinical presentations of the disease

Patients and Methods: eighteen patients with established Wilson's disease [10 males and 8 females] aged between 21 to 53 years were included in the study. The clinical picture was of neurologic type [nWD] in 11 patients [61.1%], and of the hepatic type [hWD] in 7 patients [38.9%]. All patients were subjected to careful general and neurological assessment, cognitive assessment using M.M.S.E scale and Trial Making test, ophthalmic slit lamp examination, biochemical tests including urinary copper and serum ceruloplasmin levels, abdominal ultrasound, liver biopsy [only in 5 patients], MRI of the brain and Tc-99m HMPAO brain SPECT

Results: brain MRI was abnormal in 11/18 patients [sensitivity 61.1 %]. It was abnormal in 9/11 nWD patients [sensitivity 81.8%], while it was positive in only 2/7 of hWD patients [sensitivity 28.6%]. Brain Tc-99m HMPAO SPECT was abnormal in 15 out of 18 patients [sensitivity 83.3%]. The scan was abnormal in 10/11 patients with nWD [sensitivity 90.9%] and in 5/7 of patients with hWD [sensitivity 71.4%]. The correlation between the clinical presentation of the disease, radiological, and SPECT findings still not clear in most cases

Conclusion: brain Tc-99m HMPAO SPECT and brain MRI are useful tools for evaluating patients with Wilson's disease. Brain SPECT has a higher sensitivity than brain MRI in detecting brain abnormalities, however the clinico-anatomical correlation still not established yet in many cases

[Wilson's disease in children - about 21 cases]

Wilson's disease is a familial affection, described the first time in 1912, which has an autosomic recessive transmission. It is characterized by an association of hepatic cirrhosis and neurologic manifestations caused by tissular accumulation of copper. To show clinical, genetic, diagnostic, therapeutic particularities and outcomes of this disease, we carried out a retrospective study concerning three pediatric departments in the Center of Tunisia [Kairouan, Farhat Hached and Sahloul hospitals]. We have collected 21 cases during a period of 17 years [from January 1983 to december 2000]. The finding's age of the disease ranges from 5 to 13 years [mean age 8 years and 9 months]. The sex ratio is 1,1. Consanguinity is found in 90% of cases. Finding circumstances are dominated by edematous and ascitic syndrome [28%] and by hepatomegaly [57.14%] a jaundice [19,5%], a pallor [9.52] and neurologic disorders [19% of cases]. A hepatic cytolysis was found in 38% and a decrease of prothrombin rate in 61% of cases. The ceruloplasmin concentration is lower than 200 mg/1 in 80% and a decrease in the blood rate of copper in 75% of cases. The urinary rate of copper was measured only in 9 patients; it was increased in 8 cases. The therapy consisted in D penicillamin in the first line. Outcome was marked by 3 cases of death. 18 patients are followed up and they are treated by D penicilamin

Wilson's disease presenting as status epilepticus.

A patient of Wilson's disease having neurological as well as psychiatric manifestations who presented with status epilepticus is being reported. The diagnosis was confirmed by biochemical investigations and 'face of giant panda' sign was present on MRI brain.

ATP7B mutations in families in a predominantly Southern Indian cohort of Wilson's disease patients.

OBJECTIVE: To analyze ATP7B mutations in Wilson's disease (WD) patients from the Indian subcontinent and to correlate these with WD phenotype. METHODS: We studied 27 WD patients from 25 unrelated families. Twenty-two families were from three southern Indian states - Tamil Nadu andhra Pradesh and Kerala. We applied conformation- sensitive gel electrophoresis (CSGE) to screen for the mutations in patients and their families. PCR products exhibiting aberrant patterns in CSGE were subjected to direct DNA sequencing. As siblings affected by WD within a family share identical ATP7B genotype, we compared WD phenotype among affected siblings within families. RESULTS: ATP7B mutations were detected in 22 of the 25 probands -13 were homozygotes and 9 were compound heterozygotes. Eleven novel mutations were detected. Only two common mutations were found: G3182A in 4 (16%) and C813A in 3 (12%) probands. 'Hot spots' for ATP7B mutations were exons 18 and 13. Lack of common dominant mutations prevented correlation of individual ATP7B mutations with WD phenotype. Symptomatic WD in a live sibling was not found in any family. In 8 families, a sibling died of presumed WD - in 6 of these, WD phenotype was identical to that in the proband. CONCLUSIONS: We describe the spectrum of ATP7B mutations including 11 novel mutations in Indian WD patients and document lack of a single dominant mutation. Identical WD phenotype among siblings in only 6 of 8 families with >1 child affected by WD suggests that factors other than ATP7B mutations influence WD phenotype.

Wilson's disease in Egyptian children: a single center 10-year experience

Wilson's disease [WD] is a multisystem disease with variable presentations. The aim of this work is to illustrate the diverse patterns of presentation of WD in Egypt. To the best of our knowledge, this is the first report regarding the clinical presentation of WD in Egypt. The study included all patients of WD presented to Pediatric Hepatology Unit Cairo University Children's Hospital within a period of ten years [1996-2005]. Analysis of date included thorough history, clinical examination, laboratory findings and treatment. Nine cases presented with hepatic manifestations [64.29%]; 2 with acute fulminant hepatitis and 7 with chronic hepatitis. Two cases presented with neurological manifestations [14.29%]. Three cases [21.4%] were presymptomatic siblings of patients with WD. The age range was 5 to 15 years. Eight patients [57.14%] had Kayser Fleischer ring [KF ring], but none had cataract. All patients had low serum ceruloplasmin level. Ten patients [71.42%] had high basal urinary copper in 24 hours and all had markedly elevated urinary copper in 24 hours after penicillamine [penicillamine challenge test]. The diagnosis of WD can be made provided that it is suspected in any patient presenting with obscure hepatic or neurological manifestations. Moreover, screening of asymptomatic relatives is a key point as 21.4% of our cases were presymptomatic relatives. Whether the predominance of hepatic presentation in our patients, was a real predominant pattern of presentation in Egypt or was due to center, awaits further studies

Doença de Wilson: diagnóstico clínico e sinais das "faces do panda" à ressonância magnética. Relato de caso / Wilson's disease: clinical diagnosis and \"faces of panda\" signs in magnetic resonance imaging. Case report

Homem de 25 anos de idade foi internado com sintomatologia polimorfa típica das afecções dos gânglios da base, associada a manifestações psiquiátricas. Fez uso de periciazina; no entanto, a suspensão do medicamento não melhorou a sintomatologia. Foi estabelecido o diagnóstico de doença de Wilson pela visualização do anel de Kayser-Fleischer através de exame com lâmpada de fenda e pelos exames laboratoriais que mostraram diminuição da ceruloplasmina plasmática e aumento de excreção de cobre urinário. A ressonância magnética, ponderada em T2, em cortes axiais do mesencéfalo e ponte, evidenciou imagens das "faces do panda".

Studies of mass infant screening for Wilson disease by urinary ceruloplasmin.

We found a 4-year-old boy in the screened cohort, who showed a low ceruloplasmin (CP) in urine (17 ng/mg-creatinine) and in blood (0.6 mg/dl), but his urine copper was in the normal range. Furthermore this child was diagnosed as Wilson disease (WD) by genetic analysis. Although no significant correlation was observed between urine and blood levels of CP, it is conceivable that WD may be accompanied by very low concentration of urine CP.

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.

Urinary excretion of copper and zinc among cigarette smokers

The urinary levels of cadmium [Cd], zinc [Zn] and copper [CU] were measured among eleven adult male non-smokers and thirty-eight adult male cigarette smokers to investigate the effect of cigarette smoking on the urinary excretion of Zn and Cu in relation to urinary Cd level. The cigarette smokers were classified into two groups according to the level of urinary Cd. The first group contained thirteen cases with urinary Cd levels within the normal range of non-smokers and the urinary levels of both Zn and Cu were observed also within the same range. The second group contained twenty-five cases with elevated urinary Cd levels. The latter was further subdivided into two subgroups according to the urinary levels of Zn and Cu. The results suggested that urinary Cd at a certain level may be accompanied by increased urinary excretion of both Zn and Cu among cigarette smokers

Comparison between the excretion of some metallic elements in normal and parasitized human

Twenty four hours urine samples from a total of 50 normal healthy individuals [30 males and 20 unmarried females] and a total of 70 parasitized patients [40 urinary schistosomiasis males and 30 trichomoniasis females] were analysed for zinc, copper, iron, calcium, magnesium, potassium and sodium. The results showed that urinary schistosomiasis leads to increased zinc, iron, calcium, magnesium and potassium levels but decreases the excretion of sodium, where as trichomoniasis leads to increase the excretion of zinc and sodium but decrease the excretion of copper. No significant differences were found in the biochemical element excretion between filtered and unfiltered urine samples during both infections

Prueba terapeútica con D-penicilamina en pacientes con la enfermedad de Wilson / D-penicilline therapeutic test in patients with Wilson`s disease

La D-penicilamina moviliza la mayor cantidad de cobre, desde sus depósitos, aproximadamente al tercer día de su administración, con el subsiguiente aumento en la concentración urinaria, para más tarde estabilizar el nivel de eliminación del ión del organismo. Seleccionamos prospectivamente 6 pacientes que reunían todos los criterios diagnósticos de la enfermedad de Wilson y que estaban sin tratamiento. Les practicamos la prueba con D-penicilamina para valorar su utilidad. Les administramos una dosis total de 900 mg diarios de D-penicilamina oral dividida en 3 subdosis, durante 5 días. Se les determinó la concentración de cobre en orina al tercer y quinto días. La excreción urinaria media de cobre se mantuvo en niveles muy similares en el tercero (16,41 micromoles/L) y quinto (15,54 micromoles/L) días, pero la concentración del metal eliminado en ambos intervalos fue 5 veces superior a la cupruria media (2,91 micromoles/L) que sirvió como base para diagnósticar la enfermedad. La cupruria media en los pacientes bajo prueba al tercer día no presentó diferencia significativa con respecto a las concentraciones obtenidas en el quinto día

Limites biológicos em higiene e medicina do trabalho

O controle biológico de trabalhadores expostos a agentes químicos agressivos coloca o médico do trabalho frente a uma série de problemas conjunturais e estruturais de difícil soluçäo. A partir de pesquisa onde foram analisadas urina de 58 soldadores para determinaçäo de concentraçäo de Mg, Zn, Cu, Mn, Fe, Cd, Cr, Ni säo discutidas as dificuldades da execuçäo deste controle, incluindo aspectos ambientais. Conclui-se pela importância das avaliaçöes biológicas, mas ressaltando a prioridade para as medidas ambientais de controle dos agentes químicos