Concordance rates of Wilson's disease phenotype among siblings.
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ABSTRACT:
SUBMITTER: Chabik G
PROVIDER: S-EPMC3889629 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Studies focusing on neuropsychological impairments in Wilson's disease (WD) have highlighted that patients showing neurological signs present significant deficits in a wide range of cognitive domains. Attentional and executive impairments have also been described in people with hepatic WD. However, social cognition abilities, i.e. cognitive processes required to perceive the emotions, intentions and dispositions of other people, have not been clearly investigated in WD. In this study we examined the social cognitive functioning in 19 patients with WD depending on their clinical status-Neurological versus Non-Neurological ("hepatic") forms-compared to 20 healthy controls. For the very first time, results highlighted that patients with WD had significant impairments in the three major components of social cognition: emotion recognition, Theory of Mind and attributional style. However, these deficits differ depending on the form of the disease: patients with neurological signs showed a wide range of deficits in the three components that were assessed-results notably revealed impairments in recognizing "fear", "anger", and "disgust", a significant Theory of Mind deficit and an "aggression bias"-whereas Non-Neurological patients only showed deficits on test assessing attributional bias, with a trend to react more "aggressively" to ambiguous social situations than healthy controls, as observed in Neurological WD patients, and a specific impairment in "anger" recognition. Our findings are discussed in the light of both neurocognitive impairments and brain damages, and especially those affecting the basal ganglia, as observed in people with WD.
| S-EPMC5383022 | biostudies-literature
Project description:HSD17B13 encodes hydroxysteroid 17-β dehydrogenase 13, a novel liver lipid-droplet associated protein that is involved in the regulation of lipid biosynthetic processes. A protein-truncating HSD17B13 variant (rs72613567) was shown to protect individuals from alcoholic and non-alcoholic liver disease. Since steatosis is a common feature in Wilson's disease (WD), we aimed to assess whether the HSD17B13 variant modulates the phenotypic presentation and progression of WD.MethodsThe HSD17B13:TA (rs72613567) variant was determined by allelic discrimination real-time PCR in 586 patients. The HSD17B13 genotype was correlated with the phenotypic presentation. The age of onset and the type of symptoms at presentation were used as markers of the WD phenotype.ResultsThe overall HSD17B13:TA allele frequency in patients with WD was 23.3% (273/1,172), not significantly different from the reported minor allele frequency. There was a significantly lower HSD17B13:TA allele frequency in patients with fulminant WD compared to all other phenotypic WD groups (11.0% vs. 24.0%, p < 0.01). Among the patients with fulminant WD there was a trend for a gender effect; none of the male patients carried the HSD17B13:TA allele. HSD17B13:TA allele frequency was more common in patients with minimal or no fibrosis (49 [31.1%] had simple steatosis and 20 minimal changes at biopsy) than in patients with cirrhosis or advanced fibrosis (22.3%, p = 0.025).ConclusionsThe HSD17B13:TA allele modulates the phenotype and outcome of WD. This allele likely ameliorates hepatic fibrosis and reduces the transition from copper induced hemolysis to fulminant disease in patients with WD.Lay summaryWilson's disease is a hereditary disease caused by accumulation of copper in the liver and other tissues. It presents with a variety of clinical symptoms. In this study we explored the role of a recently described gene mutation (HSD17B13:TA) which apparently protects the liver against toxins like alcohol. The results indicate that this mutation plays a role in the evolution of liver disease. Patients with Wilson's disease who carry this mutation are more likely to have mild disease, while the absence of the mutation is associated with the most severe form - fulminant Wilson's disease.
| S-EPMC7001574 | biostudies-literature
Project description:BackgroundWilson's disease (WD) is a rare autosomal recessive inherited disorder of copper metabolism. Acute liver failure (ALF) and hemolytic anemia represent the most severe presentation of WD in children. No clear genotype-phenotype correlations exist in WD. Protein-truncating nonsense, frame-shift, or splice-site variants may be associated with more severe disease. In contrast, missense variants may be associated with late-onset, less severe disease, and more neurological manifestations. Recently, a gene variant (HSD17B13:TA, rs72613567) with a possible hepatic protective role against toxins was associated with a less severe hepatic phenotype in WD.AimTo analyze the possible genotype-phenotype correlations in children with WD presented with ALF and non-immune hemolytic anemia.MethodsThe medical records of children with WD diagnosed and treated in our hospital from January 2006 to December 2020 were retrospectively analyzed. The clinical manifestations (ALF with non-immune hemolytic anemia or other less severe forms), laboratory parameters, copper metabolism, ATP7B variants, and the HSD17B13:TA (rs72613567) variant were reviewed to analyze the possible genotype-phenotype correlations.ResultsWe analyzed the data of 51 patients with WD, 26 females (50.98%), with the mean age at the diagnosis of 12.36 ± 3.74 years. ALF and Coombs-negative hemolytic anemia was present in 8 children (15.67%), all adolescent girls. The Kayser-Fleisher ring was present in 9 children (17.65%). The most frequent variants of the ATP7B gene were p.His1069Gln (c.3207A>G) in 38.24% of all alleles, p.Gly1341Asp (c.4021G>A) in 26.47%, p.Trp939Cys (c.2817G>T) in 9.80%, and p.Lys844Ter (c.2530A>T) in 4.90%. In ALF with hemolytic anemia, p.Trp939Cys (c.2817G>T) and p.Lys844Ter (c.2530A>T) variants were more frequent than in other less severe forms, in which p.His1069Gln (c.3207A>G) was more frequent. p.Gly1341Asp (c.4021G>A) has a similar frequency in all hepatic forms. For 33 of the patients, the HSD17B13 genotype was evaluated. The overall HSD17B13:TA allele frequency was 24.24%. Its frequency was higher in patients with less severe liver disease (26.92%) than those with ALF and hemolytic anemia (14.28%).ConclusionIt remains challenging to prove a genotype-phenotype correlation in WD patients. In children with ALF and hemolytic anemia, the missense variants other than p.His1069Gln (c.3207A>G) and frame-shift variants were the most frequently present in homozygous status or compound heterozygous status with site splice variants. As genetic analysis is usually time-consuming and the results are late, the importance at the onset of the ALF is questionable. If variants proved to be associated with severe forms are found in the pre-symptomatic phase of the disease, this could be essential to predict a possible severe evolution.
| S-EPMC8568583 | biostudies-literature
Project description:ObjectivesWe investigated whether eating behaviors were concordant among diverse sets of social ties.MethodsWe analyzed the socioeconomic and demographic distribution of eating among 3418 members of the Framingham Heart Study observed from 1991 to 2001. We used a data-classification procedure to simplify choices into 7 nonoverlapping patterns that we matched with information on social network ties. We used correlation analysis to examine eating associations among 4 types of peers (spouses, friends, brothers, and sisters). Longitudinal multiple logistic regression was used to evaluate evidence for peer influences on eating.ResultsOf all peer types, spouses showed the strongest concordances in eating patterns over time after adjustment for social contextual factors. Across all peers, the eating pattern most likely to be shared by socially connected individuals was "alcohol and snacks." Models estimating one's current eating pattern on the basis of a peer's prior eating provided supportive evidence of a social influence process.ConclusionsCertain eating patterns appeared to be socially transmissible across different kinds of relationships. These findings represent an important step in specifying the relevant social environment in the study of health behaviors to include eating.
| S-EPMC3222397 | biostudies-literature
Project description:BackgroundMacrophages play a significant role in liver disease development and progression. The macrophage activation marker soluble (s)CD163 is associated with severity and prognosis in a number of different acute and chronic liver diseases but has been only sparsely examined in Wilson's disease (WD). We investigated sCD163 levels in patients with acute and chronic WD and hypothesized associations with liver disease phenotype and biochemical markers of liver injury.MethodsWe investigated sCD163 in two independent cohorts of WD patients: 28 patients with fulminant WD from the US Acute Liver Failure (ALF) Study Group registry and 147 patients with chronic disease from a German WD registry. We included a control group of 19 healthy individuals. Serum sCD163 levels were measured by ELISA. Liver CD163 expression was determined by immunohistochemistry.ResultsIn the ALF cohort, median sCD163 was 10-fold higher than in healthy controls (14.6(2.5-30.9) vs. 1.5(1.0-2.7) mg/L, p < 0.001). In the chronic cohort, median sCD163 was 2.6(0.9-24.9) mg/L. There was no difference in sCD163 according to subgroups based on initial clinical presentation, i.e. asymptomatic, neurologic, hepatic, or mixed. Patients with cirrhosis at the time of diagnosis had higher sCD163 compared with those without cirrhosis (3.0(1.2-24.9) vs. 2.3(0.9-8.0) mg/L, p < 0.001); and both cohorts significantly lower than the ALF patients. Further, sCD163 correlated positively with ALT, AST, GGT and INR (rho = 0.27-0.53); and negatively with albumin (rho = - 0.37), (p ≤ 0.001, all). We observed immunohistochemical CD163 expression in liver tissue from ALF patients.ConclusionsAlthough sCD163 is not specific for WD, it was elevated in WD patients, especially in those with ALF. Further, sCD163 was higher in patients with cirrhosis compared to patients without cirrhosis and associated with biochemical markers of liver injury and hepatocellular function. Thus, macrophage activation is evident in WD and associates with liver disease phenotype and biochemical parameters of liver disease. Our findings suggest that sCD163 may be used as a marker of liver disease severity in WD patients.
| S-EPMC7331244 | biostudies-literature
Project description:BackgroundMovement disorder is common in Wilson's disease (WD), but there is no report on oromandibular dystonia (OMD). We report on frequency, severity, and MRI correlation of OMD in Wilson's disease with neurological manifestations (WDNM) and its response to treatment.MethodsConsecutive WDNM patients were included and their clinical, hematological, serum chemistry, and MRI findings were noted. Neurological severity of WD and OMD were assessed. Burke-Fahn-Marsden (BFM) score for dystonia was noted. Patients were treated with penicillamine, zinc, and multiple antidystonic drugs. Clinical improvement at 3 and 6 months was noted.ResultsOverall, 61 of 67 (91%) WDNM patients had OMD, whose median age was 13.5 years. Median severity of OMD was 2.5 (range, 1-4). Thirteen patients were anarthric and 12 unable to eat. Severity of OMD correlated with drooling (r = 0.29; P = 0.02), BFM score (r = 0.63; P < 0.001), pancytopenia (r = -0.26; P = 0.04), and serum ceruloplasmin (r = 0.33; P = 0.01), but not with location and number of MRI lesions. Compared to baseline, severity of OMD improved at 6 months (P < 0.001), but not at 3 months. None became asymptomatic. Improvement in OMD paralleled with improvement in severity grade of WDNM (r = 0.26; P = 0.04) and with BFM score (r = 0.31; P = 0.02).ConclusionOMD was a common manifestation of WDNM occurring in 91% patients, and OMD improved partially over the study period.
| S-EPMC6178763 | biostudies-literature
Project description: Not available
| S-EPMC8257181 | biostudies-literature
Project description:We report an unusual occurrence of involuntary movement involving the tongue in a patient with confirmed Wilson's disease (WD). She manifested with slow, hypophonic speech and dysphagia of 4 months duration, associated with pseudobulbar affect, apathy, drooling and dystonia of upper extremities of 1 month duration. Our patient had an uncommon tongue movement which was arrhythmic. There was no feature to suggest tremor, chorea or dystonia. It might be described as athetoid as there was a writhing quality, but of lesser amplitude. Thus, the phenomenology was uncommon in clinical practice and the surface of the tongue was seen to "ripple" like a liquid surface agitated by an object or breeze. Isolated lingual dyskinesias are rare in WD. It is important to evaluate them for WD, a potentially treatable disorder.
| S-EPMC4090856 | biostudies-literature
Project description:We used cutaneous delayed-type hypersensitivity responses, a powerful in vivo measure of cell-mediated immunity, to evaluate the relationships among cell-mediated immunity, AIDS, and polymorphisms in CCR5, the HIV-1 coreceptor. There was high concordance between CCR5 polymorphisms and haplotype pairs that influenced delayed-type hypersensitivity responses in healthy persons and HIV disease progression. In the cohorts examined, CCR5 genotypes containing -2459G/G (HHA/HHA, HHA/HHC, HHC/HHC) or -2459A/A (HHE/HHE) associated with salutary or detrimental delayed-type hypersensitivity and AIDS phenotypes, respectively. Accordingly, the CCR5-?32 allele, when paired with non-?32-bearing haplotypes that correlate with low (HHA, HHC) versus high (HHE) CCR5 transcriptional activity, associates with disease retardation or acceleration, respectively. Thus, the associations of CCR5-?32 heterozygosity partly reflect the effect of the non-?32 haplotype in a background of CCR5 haploinsufficiency. The correlations of increased delayed-type hypersensitivity with -2459G/G-containing CCR5 genotypes, reduced CCR5 expression, decreased viral replication, and disease retardation suggest that CCR5 may influence HIV infection and AIDS, at least in part, through effects on cell-mediated immunity.
| S-EPMC3071050 | biostudies-literature
Project description:Wilson's disease (WD) is a potentially fatal disorder of chronic copper toxicity, primarily affecting the liver and the brain. Judicious treatment can restore health and longevity, even in patients with severe neurological impairment. However, the disease is associated with considerable morbidity and mortality resulting from delay in diagnosis, and difficulty in pacing the medical treatment. In this article, we briefly review the diagnosis and treatment options for WD and share our experience in managing patients with WD. We focus on decoppering (copper chelation) treatment of WD and outline pragmatic strategies for patient management designed to recognize and minimize adverse effects while ensuring treatment compliance and effectiveness.
| S-EPMC6183178 | biostudies-literature