1/166. Pilot study of screening for Wilson disease using dried blood spots obtained from children seen at outpatient clinics.Wilson disease (WD) is an autosomal recessive disorder of copper accumulation leading to liver and/or brain damage. In this paper, we describe the results of a pilot study of screening for WD using ceruloplasmin determinations in dried blood samples. Specimens were collected from children aged 1 to 6 years who were seen at local paediatric outpatient clinics in the Miyagi Prefecture. We measured ceruloplasmin (CP) concentrations in 2789 children using an enzyme-linked immunosorbent assay. The mean value was 12.4 /- 3.95 mg/dl blood. Among these children, we identified two (case 1, male, 2 years old; case 2, female, 3 years old) with markedly reduced CP concentrations. Apart from low serum copper concentrations, their biochemical findings were almost normal, as were growth and development. To confirm the diagnosis, we analysed the WD gene and detected A803T/2871delC mutations in case 1 and R778L/G1035V mutations in case 2. We conclude that these children were presymptomatic WD patients. The CP level in dried blood samples from children aged 1 to 6 years appears to be a reliable marker for early detection of WD.- - - - - - - - - - ranking = 1keywords = liver (Clic here for more details about this article) |
2/166. Wilson's disease coexisting with viral hepatitis type C: a case report with histological and ultrastructural studies of the liver.Histopathological and ultrastructural findings in the liver of a female patient who suffered from Wilson's disease (WD) and viral hepatitis type C (HCV) are reported. light and electron microscopy examinations demonstrated a variety of morphological alterations--many of them frequently seen in livers of patients with WD and others that can be found in cases presenting HCV infection. The influence of coexistence of these two diseases on morphological changes is discussed.- - - - - - - - - - ranking = 6keywords = liver (Clic here for more details about this article) |
3/166. Wilson's disease (hepatolenticular degeneration).Wilson's disease, or hepatolenticular degeneration, is a rare inherited disorder of copper metabolism which usually affects young people. Excess copper accumulates in the tissues, primarily in the liver, brain, and cornea. This copper deposition results in a wide range of hepatic and neurological symptoms, and may produce psychiatric illness. Hepatic involvement often occurs in childhood, while neurological deficits generally are detected at a later age. The disease is inherited in an autosomal recessive fashion. Ocular findings are of particular importance because the corneal copper deposition, forming the Kayser-Fleischer ring,is the only pathognomonic sign of the disease. The structure of the ring and the presence of copper have been well established. An anterior capsular deposition of copper in the lens results in a characteristic sunflower cataract in some of these patients. Other ocular abnormalities have been described but are much less common. The pathogenesis of the disease and the basic genetic defect remain obscure. It is clear that there is excess copper in the tissues, but the mechanism of its deposition is unknown. It is in some way associated with a failure to synthesize the serum copper protein ceruloplasmin normally. Another theory suggests that an abnormal protein with a high affinity for copper may bind the metal in the tissues. The diagnosis may be suggested by the clinical manifestations and confirmed by the presence of a Kayser-Fleischer ring. In the absence of these findings biochemical determinations are necessary. The most important of these are the serum ceruloplasmin, the urinary copper, and the hepatic copper concentration on biopsy. Treatment consists in the administration of the copper chelating agent, penicillamine, and the avoidance of a high copper intake. This usually results in marked clinical improvement if irreversible tissue damage has not occurred. maintenance therapy for life is necessary in order to continue the negative copper balance. The detection and prophylactic treatment of asymptomatic individuals with the disease is especially important. Seven cases of Wilson's disease have been presented in order to illustrate many of the features which have been discussed, with emphasis on the ocular findings.- - - - - - - - - - ranking = 1keywords = liver (Clic here for more details about this article) |
4/166. Development of cytochrome P450 2D6-specific LKM-autoantibodies following liver transplantation for Wilson's disease -- possible association with a steroid-resistant transplant rejection episode.BACKGROUND/AIMS: Antibodies to cytochrome P450 2D6, also known as LKM1-autoantibodies, are characteristic for a subgroup of patients with autoimmune hepatitis, but can also occasionally be found in hepatitis c. We observed the occurrence of LKM1-autoantibodies 4 months after liver transplantation for Wilson's disease, in close association with a steroid-resistant rejection episode, in the absence of evidence for autoimmune hepatitis or hepatitis c. methods: Sera from several time points prior to and following transplantation were tested for LKM-reactivity by immunofluorescence, ELISA and Western blotting. Antigen specificity was confirmed by Western blotting analysis on different cytochrome P450 isoenzymes. The absence of viral hepatitis C and hepatitis G virus infection was confirmed by polymerase chain reaction. The serum of the organ donor was also tested. RESULTS: All the sera prior to transplantation and up to 4 months after transplantation were LKM-negative by all assay systems used. In the course of a steroid-resistant rejection episode at this time, the patient developed LKM antibodies at high titre (70% in inhibition ELISA) and has remained positive since (now more than 4 years). Reactivity was exclusively to the cytochrome isoenzyme 2D6. hepatitis c infection never occurred, but hepatitis G was transiently present many years prior to transplantation. The donor serum was negative for all autoantibodies and for hepatitis c and G virus infection. DISCUSSION: We here describe a patient developing LKM1-autoantibodies without evidence of autoimmune or viral hepatitis. The close temporal association with a transplant rejection episode suggests immunological mechanisms of rejection together with hepatocellular injury as a pathogenetic mechanism.- - - - - - - - - - ranking = 5keywords = liver (Clic here for more details about this article) |
5/166. Albumin dialysis: effective removal of copper in a patient with fulminant Wilson disease and successful bridging to liver transplantation: a new possibility for the elimination of protein-bound toxins.BACKGROUND: Acute liver failure may be the first manifestation of Wilson disease. If copper elimination fails, liver transplantation is the only remaining therapeutic option. Albumin dialysis, a new method for the removal of protein-bound toxins, was performed in a patient with fulminant Wilson disease. methods: An 18-year-old man with Wilson disease presented with hyperacute liver failure, hepatic encephalopathy III, oligo-anuric renal failure, haemolytic anaemia, rhabdomyolysis, pancreatitis and thrombocytopenia. He was treated with albumin dialysis using a 44 g/l albumin-containing dialysate and a slow dialysate flow rate (1-2 l/h). The other details of the technique used are similar to routine continuous veno-venous haemodiafiltration. RESULTS: One hundred and five milligrams of copper were removed by albumin dialysis within the first six treatments, resulting in normalisation of blood-copper levels. Successful treatment of the multiorgan failure was achieved. hepatic encephalopathy improved within 2 days. The patient initially refused liver transplantation. Therefore 35 additional albumin dialysis treatments were performed. Forty-three grams of bilirubin (an indicator of detoxified substances in the liver) and 196 mg of copper were removed. Multiorgan failure, in particular hepatic encephalopathy, did not recur during 59 days of treatment. Eventually, the patient agreed to liver transplantation and that was successful. CONCLUSION: Albumin dialysis is a new method for the effective treatment of fulminant Wilson disease, resulting in the removal of protein-bound toxins copper and bilirubin. It may serve as a new treatment option in hyperacute liver failure of other origin, acting as an extracorporeal detoxifier.- - - - - - - - - - ranking = 11keywords = liver (Clic here for more details about this article) |
6/166. Effect of liver transplantation on neurological manifestations in Wilson disease.BACKGROUND: liver transplantation (LT) is the sole resolutive therapy for Wilson disease (WD) and is the treatment of choice for patients with WD who have fulminant hepatic failure or end-stage cirrhosis. Although its role in managing the neurological manifestations of WD is not yet conclusive, LT has recently been advocated as a therapy for neurologically affected patients with WD with stable liver function. OBJECTIVE: To evaluate the effect of LT on the neurological manifestations of WD. observation: A 44-year-old man with WD with cirrhosis and neurological symptoms (motor dysfunction and cognitive impairment) experienced a dramatic improvement in motor function early after LT, as well as normalization of copper balance and the disappearance of Kayser-Fleischer rings. Abnormalities seen on magnetic resonance imaging scans were reversed 18 months after LT. Cognitive testing 2 years after LT showed a moderate global improvement. CONCLUSIONS: In this case, LT healed the neurological manifestations of WD. To date, this favorable result has been seen in almost 80% of cases. However, the decision to perform LT in patients with WD solely on the basis of neurological impairment must be considered experimental.- - - - - - - - - - ranking = 5keywords = liver (Clic here for more details about this article) |
7/166. Novel mutations of the ATP7B gene in Japanese patients with Wilson disease.Wilson disease (WD) is an autosomal recessive disorder characterized by copper accumulation in the liver, brain, kidneys, and corneas, and culminating in copper toxication in these organs. In this study, we analyzed mutations of the responsible gene, ATP7B, in four Japanese patients with WD. By direct sequencing, we identified five mutations, of which two were novel, and 16 polymorphisms, of which 6 were novel. The mutations 2871delC and 2513delA shift the reading frame so that truncated abnormal protein is expected. In contrast to these mutations found in patients with hepatic-type of early onset, the mutations A874V, R778L, and 3892delGTC were either missense mutations or in frame 1-amino acid deletion, and occurred in the patients with hepato-neurologic type of late onset. The mutations 2871delC and R778L have been previously reported in a relatively large number of Japanese patients. In particular, R778L is known to be more prevalent in Asian countries than in other countries of the world. Our data are compatible with the hypothesis that the mutations tend to occur in a population-specific manner. Therefore, the accumulation of the types of mutations in Japanese patients with WD will facilitate the fast and effective genetic diagnosis of WD in Japanese patients.- - - - - - - - - - ranking = 1keywords = liver (Clic here for more details about this article) |
8/166. February 2000: dementia with motor dysfunction in a patient with liver disease.Acquired (non-Wilsonian) hepatocerebral degeneration (AHCD) is an irreversible neurological condition characterized by dementia, dysarthria, and motor disturbances. It has been described in patients with severe liver disease of many causes, and notably in patients with surgically or spontaneously created porto-systemic shunts. We report a case of AHCD in a patient with end-stage liver disease due to alcohol abuse and hepatitis c. In addition, this patient showed pathologic evidence of the less commonly reported "shunt myelopathy" in the absence of a surgically created porto-systemic shunt. The myelopathy was associated with a dramatic vacuolation involving especially the deep motor cortex. Electron microscopy suggested that the vacuolation was due mainly to disruption of abnormal astrocytes.- - - - - - - - - - ranking = 6keywords = liver (Clic here for more details about this article) |
9/166. Hypersomnia in Wilson's disease: an unusual symptom in an unusual case.Wilson's disease (WD) shows a wide heterogeneity in symptoms. In this case report we present hypersomnia as a symptom of WD. The male patient's complaints as fatigue, decreased level of concentration, and highly increased demand of sleeping started at his age of 21 years. No abnormality was found at physical examination. A moderate elevation in liver function tests was found, but all the other laboratory findings were within the normal range. The marked hypersomnia was verified by 24-h cassette EEG polisomnographic monitoring. No abnormality was found at physical examination. EEG, brain CT and MRI were normal. Neither toxic nor infectious disease was detectable. The diagnosis of WD was based on decreased coeruloplasmin level, increased baseline and forced urinary excretion of copper, and decreased level of serum copper. Kayser-Fleischer ring was not detectable. D-penicillamine (DPA) was introduced. At 8-10 months after the initiation of the therapy the patient's complaints gradually resolved. The control sleep record 14 months after the initiation of the DPA therapy was normal. Five years later the patient is currently on penicillamine treatment and he is free of any symptom.- - - - - - - - - - ranking = 1keywords = liver (Clic here for more details about this article) |
10/166. Wilson's disease patients with normal ceruloplasmin levels.Wilson's disease, an inborn defect of copper metabolism, is a fatal disease unless specific treatment is given. Hepatic presentation mimics almost all kinds of liver disease and the diagnosis is sometimes problematic. The diagnosis is based on clinical findings, family history, presence of Kayser-Fleischer rings, and results of key laboratory tests such as low serum ceruloplasmin level, increased urinary copper excretion and hepatic copper content. We report four patients with Wilson's disease with hepatic manifestations with unknown there were difficulties in making the diagnosis because of normal serum ceruloplasmin levels. Inspite of normal ceruloplasmin levels and absence of Kayser-Fleischer rings, strong family history suggested Wilson's disease and the diagnosis was confirmed by increased urinary and hepatic copper amounts.- - - - - - - - - - ranking = 1keywords = liver (Clic here for more details about this article) |
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