to prospectively investigate the incidence and prevalence of Wilson disease (Wd) in Chinese han population in anhui province, to analyze the genetic mutations in individuals with Wd, and to provide basic epidemiological data regarding Wd in this Chinese han population.between november 2008 and June 2010, individuals aged from 7 to 75 years were screened for the cornea K-f ring in both eyes using slit lamp examination and random sampling methods based on age stratification and cluster level 1. the participants were from anhui province’s hanshan County, Jinzhai County, and lixin County. the clinical manifestations of the brain, liver, kidney, skin, and other organs in each individual were also determined. individuals with positive K-f rings and clinical manifestations indicative of Wd underwent copper biochemistry evaluations, abdominal ultrasound testing, and ATP7B gene mutation screening to confirm or exclude the diagnosis of Wd.of 153,370 individuals investigated in this study, nine were diagnosed with Wd. in these Wd individuals, three cases had neurological symptoms, one has hepatic symptoms, one was hepatic and neurological combined, and the other four cases were presymptomatic. of the eight individuals in whom genetic mutations were detected, seven individuals had mutations in the ATP7B gene. the other individual had no ATP7B gene mutations but her copper biochemical test results met the diagnostic criteria for Wd. the incidence and prevalence of Wd in this population were approximately 1.96/100,000 and 5.87/100,000 respectively.the Chinese han population had a higher average prevalence of Wd than the populations of the united States or europe.
Abstract Background and aim: Significantly reduced serum ceruloplasmin (Cp) is the most important clue in the diagnosis of Wilson disease (WD) and is well known to clinicians. The false increase in Cp in some WD patients, which overlaps with that in non-WD liver disease patients, decreases the diagnostic accuracy. The aims of our study were to understand the factors associated with Cp normalization in WD patients and to identify these WD patients using usual predictors. Methods: We retrospectively screened individuals with serum Cp ≥140 mg/L from 1032 WD patients who were hospitalised for the first time. Logistic regression analyses were performed in a case-control study between the WD cohort and another liver disease cohort to explore the independent risk factors for WD diagnosis and establish a regression model to identify them. The follow-up medical records of the WD cohort were subjected to mixed effects model analysis in a longitudinal study to discover factors associated with Cp normalisation. Results: Eighty-six WD patients and 353 of their medical records and another 98 non-WD liver disease patients were included in the present study. Cp normalisation was significantly associated with the copper burden and liver function indexes, such as urinary copper, γ-glutamyltransferase, and albumin ( p ≤0.001). Logistic regression analysis showed that age and serum creatinine ( p ≤0.001) were independent risk factors associated with WD. The AUC value of regression model in total cohort was 0.926 ( p ≤0.001). At a cutoff value of ≥ 0.617 and ≥ -1, the positive and negative predictive values were both 90.8% for WD. Conclusion: Increased serum Cp in WD patients is related to excessive copper burden and hepatic injury, and common tests can effectively distinguish WD patients from other liver injury patients.
Abstract Objective To understand the relationship between the two types of mutations in patients with Wilson disease (WD) and clinical practice, and to search for the clinical biological markers of the two types of mutations. Methods The hospitalized patients, who were in the affiliated hospital of neurology institute of anhui university of traditional Chinese medicine from May 2014 to May 2019, with p. arg778leu or p. pro992leu homozygous mutation type of neurologic WD, were selected and underwent demographic, clinical manifestations, serological indicators and brain MR imaging(MRI) data were analyzed to compare the differences of the two mutant types of neurologic WD. ResultsThe group of 103 patients with neurologic WD join in this research, including p.A rg778Leu mutant WD 65 cases and p.P ro992Leu mutant WD 38 cases. The two types of mutations in the WD demographic, clinical manifestation and most serological index indifference, and brain MRI findings have significant differences, especially the p.A rg778Leu mutant WD damage the thalamus(χ2 =17.834, P<0.001), midbrain(χ2 =12.579, P<0.001) and pons(χ2 =10.605, P=0.001)p.P ro992Leu mutant WD have obvious difference, the results of multivariate analysis were also different (P<0.05). Conclusions The demography, clinical features and serology of neurologic WD have nothing to do with its gene mutation type, and the MRI manifestations of brain are related to its gene mutation type, among which the ATP7B gene p.arg778leu mutation is more likely to involve thalamus, midbrain and pons.
To study the clinical effect of six antidotes against heavy metal poisoning in Wilson’s disease (WD). 852 cases of WD patients were divided into six groups (GSH group, DMS group, CaNa_(2)EDTA group, DMPS group, PCA group and DMSA group) randomly. The urinary copper, clinical effects and side effect of each group were observed, and these results were compared between pre-treatment and l: post-treatment in each group. Except for GSH group (P>0.05), the average urinary copper levels of other groups increased. The urinary copper levels from high to low were as follows: DMPS group (48.68±20.67)µmol•24h~(-1), PCA group (30.04±10.51)µmol•24h~(-1), DMS group (24.30±8.60)µmol•24h~(-1), DMSA group (18.25±7.73)µmol•24h~(-1) and CaNa_(2)EDTA group (10.58±4.67)µmol•24h~(-1). There were significant differences between the pre-treatment and post-treatment groups (P<0.01). These antidotes also had some influences on metabolism of zinc, ferrum and calcium. The clinical effective rate of each group which had significant difference (x~(2)=73.5, P<0.01) from high to low w as follows: DMPS group (78.9％), DMS group (74.5％), PCA group (71.3％), DMSA group (69.1％). CaNa_(2)EDTA group (53.7％), and GSH group (28.8％). The rates of side effect of each group from high to low were as follows: PCA group (44.5％), DMPS group (43.8％), DMS group (42.2％), DMSA group (41.2％), and CaNa_(2)EDTA group (39.8％), and they were significant differences compared with GSH group (x~(2)=33.6, P<0.01). The common side effects include digestive dysfunction, allergic reaction, hemorrhagic tendency, cytopenia, liver dysfunction, renal dysfunction, and so on. The urinary copper level and clinical effect of these antidotes suggest that PCA is the best among oral drags, DMSA takes the second place, DMPS is the best among injection drugs, DMS takes second place, CaNa_(2)EDTA is mild, GSH is effectless.
Wilson's disease (WD) is an inherited disease caused by mutations in ATP7B and is characterized by the pathological accumulation of copper in the liver and brain. Common clinical manifestations of WD include a wide range of liver disease and neurological symptoms. In some patients, psychiatric symptoms may be the only manifestation at the time of diagnosis. The clinical features of WD are highly variable and can mimic any disease of internal medicine. Therefore, for unexplained medical diseases, the possibility of WD should not be ignored. Early diagnosis and treatment can improve the prognosis of WD patients and reduce disability and early death. Gene sequencing is becoming a valuable method to diagnose WD, and if possible, all WD patients and their siblings should be genetically sequenced. Copper chelators including D-penicillamine, trientine, and dimercaptosuccinic acid can significantly improve the liver injury and symptoms of WD patients but may have a limited effect on neurological symptoms. Zinc salts may be more appropriate for the treatment of asymptomatic patients or for the maintenance treatment of symptomatic patients. High-quality clinical trials for the drug treatment of WD are still lacking, therefore, individualized treatment options for patients are recommended. Individualized treatment can be determined based on the clinical features of the WD patients, efficacy and adverse effects of the drugs, and the experience of the physician. Liver transplantation is the only effective method to save patients with acute liver failure or with severe liver disease who fail drug treatment.
In this study, we analyzed the difference of intestinal flora polymorphisms between Wilson's disease (WD) patients and healthy people by high-throughput sequencing technology, and explored the correlation between WD and intestinal flora polymorphism. A total of 22 cases of WD patients and 22 healthy persons as control were recruited. The total DNA was extracted from the fecal specimens of all the subjects, V4 high variable region of 16S rRNA gene was amplified and sequenced by high-throughput sequencing. The sequencing results were analyzed by α diversity and β diversity. The unweighted UniFrac distance matrices were calculated and trees were built by unweighted-pair group method with arithmetic mean (UPGMA). A total of 2,548,262 sequences were obtained after the data are optimized, the average sequences in the WD group was 36,836 ± 4104 and it was 35,051 ± 3075 in the normal control group, there was no significant difference in the average sequence number between the 2 groups. OTU analysis showed that 2663 OTU were obtained in WD group, and 3271 OTU were obtained in the control group, of which 941 were common OTU. Colony diversity analysis showed that the intestinal flora of WD group and control group belonged to 5 phyla, they were Bacteroidetes, Firmicutes, Proteobacteria, Fusobacteria, and Tenericutes, respectively. In WD group, the abundance of Bacteroidetes was significantly lower than that of the control group (67.19% vs 76.75%, P < .001), and the abundance of Firmicutes (26.18% vs 19.83%, P < .001), Proteobacteria (4.31% vs 3.09%, P < .05), Fusobacteria (1.88% vs 0.04%, P < .001) were significantly higher than that of control group. Compared with the control group at the level of the genus, the abundance of Bacteroides (4.85% vs 4.6%, P < .05), Faecalibacterium (2.92% vs 2.13%, P < .05), Megamonas (0.84% vs 0.22%, P < .001), Lachnospira (0.16% vs 0.09%, P < .001) significantly increased in WD group, while the abundance of Prevotella (1.63% vs 2.48%, P < .001), Roseburia (0.75% vs 1.39%, P < .001) and Phascolarctobacterium (1.72% vs 2.45%, P < .001) significantly decreased in WD group. PCoA and UPGMA tree analysis showed that there were significant differences of gut microbial compositions between the 2 groups. The diversity and composition of intestinal flora in the WD patients were significantly lower than those in the healthy controls, and the diversity of intestinal flora may be associated with the presence of WD.
To further explore the etiological mechanism of Wilson's disease (WD) by comparing the changes of biliary trace elements and its clinical phenotype.WD patients with different types and conditions (n = 20), non-WD patients with chronic liver damage (n = 22), and healthy volunteers (n = 10; used as controls) were studied. Biliary samples were taken by duodenal drainage. Atom absorption spectrophotometer was used to assay the copper and zinc content of each sample.In WD, the copper content and copper/zinc ratio of biliary juice were evidently lower than those of non-WD patients with chronic liver damage and of healthy controls (F = 14.76, 25.4; 14.92, 26.2 respectively; P < 0.01), while the biliary zinc level had no significant difference from the two non-WD control groups (P > 0.05). There were significant differences in biliary copper excretion among patients with different types and conditions (F = 3.75, P < 0.05; F = 6.20, P < 0.01).Copper excretion by liver and the biliary system decreases obviously in WD, which plays a key role in the phenotypic copper retention, and the biliary copper retention is closely related with the severity of hepatic injury and illness.
Objective To identify the incidence and morbidity rates of haptolenticular degeneration (HLD) at Hanshan County, Anhui Province. Methods According to the principles of age stratification,cluster and random sampling, a total of 112 810 subjects were screened by cornea slit-lamp examination during the period of November 2008 to October 2009. The subjects were from recruited from schools,factories, communities, institutions and villages at Hanshan County. And they belonged to the age group of 7 -75 years. At the same time, each subject was evaluated by the clinical examination with regards to the presence of such clinical manifestations as brain, liver, kidney, skin and other organ damage. And the examinations of copper biochemistry and abdominal ultrasound were performed for those subjects with K-F rings or their clinical manifestations suspicious of HLD. In order to confirm or exclude HLD, the penicillamine challenge test (PCT) was performed if necessary. Results Seven HLD patients had a definite diagnosis of HLD. There were classical Wilson type ( n = 1 ), peudosclerosis type ( n = 1 ), mental disorder type (n = 1 ) , liver type (n = 1 ) and presymptomatics (n = 3). The incidence rate was 2.66/100 000 and the prevalence rate 6.21/100 000 at Hanshan County, Anhui Province. Conclusion HLD is a common disease. In order to avoid a misdiagnosis and prevent an incorrect treatment, physicians should pay more attention to this curable disease and try their best to achieve early detection, early diagnosis and early treatment.
Key words:
Haptolenticular degeneration; Slit-lamp examination; Epidemiologic study
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