Analysis of clinical and biochemical spectrum of Wilson Disease patients (original) (raw)
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Scripta Scientifica Medica, 2014
PURPOSE: Wilson disease (WD) is an autosomal recessively inherited disorder of copper accumulation and toxicity. Its recognition is easy in the presence of typical clinical presentations. Unexplained liver test abnormalities are a diagnostic challenge and require more examinations. The objective of this study is to assess the diagnostic value of ceruloplasmin, 24-hour urine copper excretion and Leipzig scoring system in WD. MATERIAL AND METHODS: Sixty-five patients with WD (22 females and 43 males) and a control group of 17 patients with other chronic liver diseases (CLD) were analyzed. The values of the parameters of copper metabolism and Leipzig scoring system were evaluated. RESULTS: Average ceruloplasmin level was under 0,2 g/L and 24-hour urinary copper concentration was increased. D-penicillamine challenge test showed a mean value of 17,4 µmol/24 hours of urinary copper excretion in WD patients versus 5,46 µmol/24 hours in CLD ones. According to the Leipzig scoring diagnostic criteria, 58 WD patients (89,23% of the cases) presented with a score ≥4 (maximal value of 12). Score 3 was found out in seven patients, however, the exclusion of other etiology and the clinical course of the disease confirmed the diagnosis. The control subjects presented with a score ≤3 as it was ≤2 in 76,5% of the cases. CONCLUSION: Our results confirm the diagnostic value for WD of the Leipzig scoring system combined with clinical symptoms, laboratory parameters of copper metabolism, genetic testing and liver biopsy in clinical practice.
Striking variability of hepatic copper levels in fulminant hepatic failure
Journal of Gastroenterology and Hepatology, 1992
Two cases of acute hepatic failure are reported in which the diagnosis of Wilson's disease was considered because of low serum ceruloplasmin, low serum copper levels and high 24 h urinary copper. Case 1 had Kayser-Fleischer rings, haemolysis and a high 24 h urinary copper, and so Wilson's disease was confidently diagnosed. Case 2 had high urinary copper excretion, but [64Cu] study indicated a 24 : 2 h ratio of 0.7 and made the diagnosis of Wilson's disease uncertain. Both patients underwent orthotopic hepatic transplantation, and multiple biopsies were taken from the resected specimen in order to estimate hepatic copper levels. In both cases, hepatic copper levels revealed considerable variation: 0.8-5.2 pmol/g dry wt (case 1) vs 0.02-12.65 pmol/g dry wt (case 2). In case 1, only two of 14 levels were within the diagnostic range for Wilson's disease (> 4 pmol/g dry wt), whereas hepatic copper levels in case 2 were in the Wilsonian disease range in three of 16 specimens. These results were in contrast to uniformly high hepatic copper levels in one patient with established cirrhosis secondary to Wilson's disease and two cases of primary biliary cirrhosis. This report indicates that hepatic copper levels vary greatly in acute liver failure, and that estimates from a single biopsy specimen may be misleading as to the cause of the underlying liver disease.
Re-evaluation of the Diagnostic Criteria for Wilson Disease in Children With Mild Liver Disease
2010
The diagnosis of Wilson disease (WD) is challenging, especially in children. Early detection is desirable in order to avoid dramatic disease progression. The aim of our study was to re-evaluate in WD children with mild liver disease the conventional diagnostic criteria and the WD scoring system proposed by an international consensus in 2001. Forty children with WD (26 boys and 14 girls, age range 5 1.1-20.9 years) and 58 age-matched and sex-matched patients with a liver disease other than WD were evaluated. Both groups were symptom-free and had elevated aminotransferases as predominant signs of liver disease. In all WD patients, the diagnosis was supported by molecular analysis, the liver copper content, or both. A receiver operating characteristic (ROC) analysis of ceruloplasmin at the cutoff value of 20 mg/dL showed a sensitivity of 95% [95% confidence interval (CI) 5 83%-99.4%] and a specificity of 84.5% (95% CI 5 72.6%-92.6%). The optimal basal urinary copper diagnostic cutoff value was found to be 40 lg/24 hours (sensitivity 5 78.9%, 95% CI 5 62.7%-90.4%; specificity 5 87.9%, 95% CI 5 76.7%-95%). Urinary copper values after penicillamine challenge did not significantly differ between WD patients and control subjects, and the ROC analysis showed a sensitivity of only 12%. The WD scoring system was proved to have positive and negative predictive values of 93% and 91.6%, respectively. Conclusion: Urinary copper excretion greater than 40 lg/24 hours is suggestive of WD in asymptomatic children, whereas the penicillamine challenge test does not have a diagnostic role in this subset of patients. The WD scoring system provides good diagnostic accuracy. W ilson disease (WD) is an autosomal recessive disorder of copper metabolism caused by mutations in a gene [ATPase, Cuþþ transporting, beta polypeptide (ATP7B)] encoding a copper-transporting, P-type ATPase. 1 This disease leads to progressive copper accumulation in the liver and subsequent deposition in other organs, such as the nervous system, corneas, kidneys, bones, and joints. The distribution of the metal in diverse organs over time accounts for the wide range of clinical manifestations. 2 In the pediatric age bracket, most cases have a hepatic presentation. In the available series, the percentage of WD children presenting with isolated elevated serum aminotransferases ranges from 14% to 88%; this depends on the health policy and the type of health care provided. 3-5 However, there is evidence that alterations in liver function tests may precede the onset of symptoms for a considerable time. Neurological symptoms are more frequent in adolescents and young adults 6-8 and are found in only 4% to 6% of pediatric cases with hepatic onset. If WD is not recognized and adequately treated, the progression of hepatic and neurological damage can be very rapid, and fulminant liver failure can occur. Therefore, the prompt detection of this condition is vital. Unfortunately, the diagnosis of WD is an especially challenging task in children because the conventional criteria established for adults are not always appropriate for children. In particular, basal urinary copper excretion in most WD children is lower than the extensively accepted cutoff value of 100 lg/24
Metallomics, 2020
Wilson disease (WD) is an autosomal recessive disorder of copper (Cu) metabolism. The gene responsible for WD, ATP7B, is involved in the cellular transport of Cu, and mutations in the ATP7B gene induce accumulation of Cu in the liver and ultimately in the brain. In a pilot study, the natural variations of copper stable isotope ratios (65Cu/63Cu) in the serum of WD patients have been shown to differ from that of healthy controls. In the present study, we challenged these first results by measuring the 65Cu/63Cu ratios in the blood of treated (n = 25), naïve patients (n = 11) and age matched healthy controls (n = 75). The results show that naïve patients and healthy controls exhibit undistinguishable 65Cu/63Cu ratios, implying that the Cu isotopic ratio cannot serve as a reliable diagnostic biomarker. The type of treatment (d-penicillamine vs. triethylenetetramine) does not affect the 65Cu/63Cu ratios in WD patients, which remain constant regardless of the type and duration of the tre...
Scandinavian Journal of Gastroenterology, 2013
Background and aims. Determination of hepatic copper (Cu) concentration is important in Wilson's disease (WD) diagnosis. The aim of this study was to evaluate uneven distribution of liver Cu concentration and the utility of double-sample biopsy in WD diagnosis. Methods. Thirty-five WD patients (20 male; mean age 41 ± 9 years) were enrolled in the study and double-liver samples for biopsy were obtained. A further 30 WD patients, in whom Cu determination was performed using single-liver samples, were also enrolled as controls. Results. A marked difference in hepatic Cu concentration was observed between the two sample groups (p < 0.0001). This difference is statistically significant for all levels of liver fibrosis (p < 0.001) and for the comparison of hepatic and neurological phenotypes (p < 0.01). The sensitivity of the Cu concentrations obtained from the double-sample biopsies for the conventional cutoff value of 250 mg/g dry weight of tissue was 85.7% compared to 80% in the single-sample biopsies. By lowering the cutoff value from 250 to 50 mg/g of dry weight of tissue, the sensitivity of Cu content to diagnose WD increased to 97% for double-sample liver biopsy compared to 93% for single-sample liver biopsy. Conclusions. Liver Cu content was unevenly distributed in the WD subjects, irrespective of fibrosis levels and disease phenotypes; hence WD can be misdiagnosed using single-sample liver Cu measurement. Double-sample biopsy sensitivity is greater than that obtained with single-sample biopsy and should therefore be considered to evaluate liver Cu concentration at initial diagnosis in all patients.
A Case Report on Wilson’s Disease: A Rare Clinical Condition of Copper Deposition in Liver
International Journal of Pharmacy and Pharmaceutical Sciences, 2021
Wilson’s disease is a rare inherited disorder and is characterized by the accumulation of copper in various tissues and also in organs like the liver, brain, kidneys and cornea. Symptoms in paediatrics characteristically appear with hepatic involvement. In this case we have discussed about an eleven-year-old male child, who was presented to the Paediatric department in a tertiary care hospital with chief complaints of yellowish discoloration of eyes, dark coloured urine and high grade fever. Due to the accumulation of copper there were decreased levels of ceruloplasmin and there was an increased 24 hour urinary copper, which confirms the Wilson’s disease in this child. Child was treated with Cephalosporin antibiotics, vitamins, laxative, and bile acid sequestrants. Child showed gradual improvement in clinical symptoms and got discharged without any further event. Quality of evidence was assessed according to the GRADE system. Early diagnosis and management helped to prevent serious ...
International Journal of Pharmacy and Pharmaceutical Sciences, 2021
Wilson's disease is a rare inherited disorder and is characterized by the accumulation of copper in various tissues and also in organs like the liver, brain, kidneys and cornea. Symptoms in paediatrics characteristically appear with hepatic involvement. In this case we have discussed about an eleven-year-old male child, who was presented to the Paediatric department in a tertiary care hospital with chief complaints of yellowish discoloration of eyes, dark coloured urine and high grade fever. Due to the accumulation of copper there were decreased levels of ceruloplasmin and there was an increased 24 hour urinary copper, which confirms the Wilson's disease in this child. Child was treated with Cephalosporin antibiotics, vitamins, laxative, and bile acid sequestrants. Child showed gradual improvement in clinical symptoms and got discharged without any further event. Quality of evidence was assessed according to the GRADE system. Early diagnosis and management helped to prevent serious complications.