Wilson's Disease Patients Research Articles

Free water imaging as a novel biomarker in Wilson's disease: A cross-sectional study

BackgroundThe bi-tensor free water imaging may provide more specific information in detecting microstructural brain tissue alterations than conventional single tensor diffusion tensor imaging. The study aimed to investigate microstructural changes in deep gray matter (DGM) nuclei of Wilson's disease (WD) using a bi-tensor free water imaging and whether the findings correlate with the neurological impairment in WD patients. MethodsThe study included 29 WD patients and 25 controls. Free water and free water corrected fractional anisotropy (FAT) in DGM nuclei of WD patients were calculated. The correlations of free water and FAT with the Unified WD Rating Scale (UWDRS) neurological subscale of WD patients were performed. ResultsFree water and FAT values were significantly increased in multiple DGM nuclei of neurological WD patients compared to controls. WD patients with normal appearing on conventional MRI also had significantly higher free water and FAT values in multiple DGM nuclei than controls. Positive correlations were noted between the UWDRS neurological subscores and free water values of the putamen and pontine tegmentum as well as FAT values of the dentate nucleus, red nucleus, and globus pallidus. In addition, the measured free water and FAT values of specific structures also showed a positive correlation with specific clinical symptoms in neurological WD patients, such as dysarthria, parkinsonian signs, tremor, dystonia, and ataxia. ConclusionsFree water imaging detects microstructural changes in both normal and abnormal appearing DGM nuclei of WD patients. Free water imaging indices were correlated with the severity of neurological impairment in WD patients.

Technical Study of Automated High-Throughput High-Sensitive Ceruloplasmin Assay on Dried Blood Spots-Reinstate the Potential Use for Newborn Screening of Wilson Disease.

In this study, we modified a fully automatic immunoassay on ceruloplasmin concentration on dried blood spots (DBS) to increase its analytical sensitivity in order to accurately differentiate newborns from true Wilson disease (WD) patients. Modifications to the assay parameters of the Roche/Hitachi Cobas c systems immunoturbidimetric assay are adjusted to lower the limit of quantitation to 0.60 mg/L from 30 mg/L. This enables sensitive measurement of ceruloplasmin in eluent after DBS extraction. In addition, reference intervals and receiver operating characteristic curve analysis for diagnostic cut-off were established using DBS of neonates and WD adult patients. After DBS whole blood calibration, the 95th percentile of the reference interval for newborns was 86-229 mg/L. The cut-off value of 54 mg/L was found to be the most optimal point for differentiating true adult WD from newborn controls. This test shows a high area under curve of 1.000 with 100% sensitivity and specificity in differentiating normal newborns from WD adult samples. However, the results should be further validated with true newborn WD patient samples together with the consideration of other factors that can also lead to low ceruloplasmin levels. This test shows application potential in newborn screening for WD, which can save lives through early identification and timely treatment.

PCR65 Development of a Patient-Reported Outcome Measure in Wilson Disease

Wilson Disease is a rare disorder in which a mutation of ATP7B causes copper to accumulate in the blood, resulting in liver disease and neurological symptoms. The objective of this research was to confirm the content validity of the Wilson Disease Functional Rating Scale – Patient Report (WDFRS-PR) for use in the Wilson Disease patient population.

Disrupted topological organization of the motor execution network in Wilson's disease.

There are a number of symptoms associated with Wilson's disease (WD), including motor function damage. The neuropathological mechanisms underlying motor impairments in WD are, however, little understood. In this study, we explored changes in the motor execution network topology in WD. We conducted resting-state functional magnetic resonance imaging (fMRI) on 38 right-handed individuals, including 23 WD patients and 15 healthy controls of the same age. Based on graph theory, a motor execution network was constructed and analyzed. In this study, global, nodal, and edge topological properties of motor execution networks were compared. The global topological organization of the motor execution network in the two groups did not differ significantly across groups. In the cerebellum, WD patients had a higher nodal degree. At the edge level, a cerebello-thalamo-striato-cortical circuit with altered functional connectivity strength in WD patients was observed. Specifically, the strength of the functional connections between the cerebellum and thalamus increased, whereas the cortical-thalamic, cortical-striatum and cortical-cerebellar connections exhibited a decrease in the strength of the functional connection. There is a disruption of the topology of the motor execution network in WD patients, which may be the potential basis for WD motor dysfunction and may provide important insights into neurobiological research related to WD motor dysfunction.

Significant heterogeneity in the diagnosis and long-term management of Wilson disease: Results from a large multicenter Spanish study

There is uncertainty regarding Wilson's disease (WD) management. ObjectivesTo assess, in a multicenter Spanish retrospective cohort study, whether the approach to WD is homogeneous among centers. MethodsData on WD patients followed at 32 Spanish hospitals were collected. Results153 cases, 58% men, 20.6 years at diagnosis, 69.1% hepatic presentation, were followed for 15.5 years. Discordant results in non-invasive laboratory parameters were present in 39.8%. Intrahepatic copper concentration was pathologic in 82.4%. Genetic testing was only done in 56.6% with positive results in 83.9%. A definite WD diagnosis (Leipzig score ≥4) was retrospectively confirmed in 92.5% of cases. Chelating agents were standard initial therapy (75.2%) with frequent modifications (57%), particularly to maintenance zinc. Enzyme normalization was not achieved by one third, most commonly in the setting of poor compliance, lack of genetic mutations and/or presence of cardiometabolic risk factors. Although not statistically significant, there were trends for sex differences in number of diagnosed cases, age at diagnosis and biochemical response. ConclusionsSignificant heterogeneity in diagnosis and management of WD patients emerges from this multicenter study that includes both small and large reference centers. The incorporation of genetic testing will likely improve diagnosis. Sex differences need to be further explored.

Botulinum toxin type A treatment of four cases of Wilson disease with lower limb dystonia: A prospective study

Botulinum toxin type A (BoNT-A) has been recommended in various neurological disorders as a useful tool for alleviating dystonia. In Wilson disease (WD) patients with dystonia, BoNT-A injection can be used as a treatment modality when conventional treatment is ineffective for alleviating symptoms. The purpose of this study was to thoroughly evaluate the efficacy of BoNT-A injection in treating WD complicated by lower extremity dystonia. The efficacy of these injections was assessed by clinical scales, surface electromyography (EMG), and gait analysis. A comparative analysis of all gait parameters, EMG parameters, and clinical scales revealed a significant increase in velocity, decrease in integrated EMG (iEMG), and improvement in modified Ashworth scale (MAS), Burke Fahn Marsden (BFM), and activities of daily living (ADL) scores (all P < 0.05). Overall, our findings indicated that BoNT-A injection led to marked relief of symptoms in patients with WD with lower extremity dystonia.

Clinical features and power spectral entropy of electroencephalography in Wilson's disease with dystonia.

To study the clinical features and power spectral entropy (PSE) of electroencephalography signals in Wilson's disease (WD) patients with dystonia. Several scale evaluations were performed to assess the clinical features of WD patients. Demographic information and electroencephalography signals were obtained in all subjects. 34 WD patients with dystonia were recruited in the case group and 24 patients without dystonia were recruited in the control group. 20 healthy individuals were included in the healthy control group. The mean body mass index (BMI) in the case group was significantly lower than that in the controls (p <.05). The case group had significantly higher SAS, SDS, and Bucco-Facial-Apraxia Assessment scores (p <.05). Total BADS scores in the case group were lower than those in the control group (p <.01). Note that 94.11% of the case group presented with dysarthria and 70.59% of them suffered from dysphagia. Dysphagia was mainly related to the oral preparatory stage and oral stage. Mean power spectral entropy (PSE) values in the case group were significantly different (p <.05) from those in the control group and the healthy group across the different tasks. The patients with dystonia were usually accompanied with low BMI, anxiety, depression, apraxia, executive dysfunction, dysarthria and dysphagia. The cortical activities of the WD patients with dystonia seemed to be more chaotic during the eyes-closed and reading tasks but lower during the swallowing stages than those in the control group.

Laboratory and clinical evaluation of a microarray for the detection of ATP7B mutations in Wilson disease in China.

Wilson disease (WD) is an autosomal recessive copper metabolic disorder caused by mutations in ATP7B. Sanger sequencing is currently used for ATP7B variant identification. However, the ATP7B gene contains 21 exons, which makes sequencing of the entire gene both complex and time-consuming. Therefore, a simpler assay is urgently needed. We performed a laboratory and clinical evaluation of an oligonucleotide microarray for the detection of 24 ATP7B recurrent mutations (except p.P992L) in Chinese patients with WD. The accuracy of the microarray was evaluated by screening for ATP7B mutations in 126 patients including 106 suspected WD samples and 20 patients with other liver diseases as negative control. Results were confirmed by Sanger sequencing. We established a reliable microarray system for the rapid detection of the 24 ATP7B mutations, with a sensitivity of 30 ng/test genomic DNA and specificity of 100% for all loci; the coefficient of variation in repeatability tests was <10%. Clinical evaluation showed an overall concordance between the microarray detection and sequencing of 100%, and 81.13% (86/106) of suspected WD cases showed ATP7B mutations by microarray detection. Microarray and Sanger sequencing identified p.R778L (50.94%), p.A874V (17.92%), p.P992L (11.32%), p.V1106I (11.32%), and p.I1148T (6.60%) as the most common mutations in WD patients. Our microarray system is customizable and easily used for high-throughput detection of certain recurrent ATP7B mutations, providing a simpler method suitable for WD genetic diagnosis in China.

S3309 Acute on Chronic Liver Failure From Wilson’s Disease After Initial Therapy with Ammonium Tetrathiomolybdate Followed by Zinc Monotherapy for 35 Years: A Case Report

Introduction: Wilson’s disease (WD) is an inherited disease of toxic accumulation of Cu mainly affecting the brain and liver. We describe a case of acute on chronic liver failure caused by WD despite being stable on Zn maintenance therapy for 35 years after initial treatment with ammonium (NH4) tetrathiomolybdate. Case Description/Methods: A 58-year-old Caucasian male with WD presented to a local hospital with acute onset of jaundice and dark urine. He is a minimal alcohol drinker. He had no exposures to hepatotoxicity and no prior evidence of liver fibrosis or decompensation. He was diagnosed WD at age 18 with neurologic symptoms and was treated in a clinical trial with NH4 tetrathiomolybdate at the time of diagnosis followed by Zn monotherapy. His Zn dosage was monitored by his PCP based on its level. On admission, his vitals were stable. Exam revealed jaundice, scleral icterus, and abdominal distension. No sign of encephalopathy or asterixis. Labs were notable for INR 2.4, ALP/AST/ALT 86/148/47 IU/L, Tbili 12.6 mg/dL, Cr 0.9 mg/dL, elevated Cu, and normal ceruloplasmin. CT noted cirrhotic liver morphology. On Day 4, he was transferred to our hospital for an urgent liver transplant (LT) evaluation. On arrival, his condition rapidly progressed with active hemolysis and elevated Tbili (peaked at 60.1) and Cr (Figure 1). Other precipitating causes including viral and autoimmune hepatitis were ruled out. On Day 5, he was sent to ICU for dialysis and was listed for transplant as Status 1A. On Day 8, he successfully underwent deceased donor LT. Liver explant showed cholestatic hepatitis on chronic hepatitis with cirrhosis consistent with WD. On Day 22, he was discharged home. Discussion: NH4 tetrathiomolybdate is proposed to be a more efficacious treatment option for neurologic predominant WD but it is not yet commercially available. Zn monotherapy is shown to be comparable to penicillamine in preventing neurologic and hepatic decompensation by inhibiting Cu uptake by intestinal mucosa. Close monitoring is paramount for patients on Zn due to risk of treatment failure. AASLD and EASL recommend monitoring liver function test, serum Cu, ceruloplasmin and physical exam twice yearly, and urine Cu yearly. However, parameters for treatment failure of Zn need to be clearly defined to consider alternative treatment before disease progression occurs. LT is the only effective option for WD patients with decompensated liver disease unresponsive to medical therapy. One-year survival following LT ranges from 79-87%.Figure 1.: Trend of patient’s total bilirubin, creatinine, and INR during hospitalization.

Serum neurofilament light chain and initial severity of neurological disease predict the early neurological deterioration in Wilson’s disease

BackgroundIn Wilson’s disease (WD), early neurological deterioration after treatment initiation is associated with poor outcomes; however, data on this phenomenon are limited. Our study analysed the frequency and risk factors of early neurological deterioration in WD.MethodsEarly neurological deterioration, within 6 months from diagnosis, was defined based on the Unified Wilson’s Disease Rating Scale (UWDRS): any increase in part II or an increase of ≥ 4 in part III. In total, 61 newly diagnosed WD patients were included. UWDRS scores, brain magnetic resonance imaging (MRI) scores, copper metabolism parameters, treatment type and serum neuro-filament light chain (sNfL) concentrations at diagnosis were analysed as potential risk factors of early deterioration.ResultsEarly neurological deterioration was observed in 16.3% of all WD patients; all cases of worsening occurred in the neurological phenotype (27.7%). Higher scores were seen in those who deteriorated compared with those who did not for UWDRS part II (4.3 ± 5.0 vs 2.0 ± 5.9; p < 0.05), UWDRS part III (21.5 ± 14.1 vs 9.3 ± 16.4; p < 0.01) and MRI-assessed chronic damage (3.2 ± 1.6 vs 1.4 ± 2.2; p = 0.006); all these variables indicated the initial severity of neurological disease. Pre-treatment sNfL concentrations were significantly higher in patients who deteriorated compared with those who did not (33.2 ± 23.5 vs 27.6 ± 62.7 pg/mL; p < 0.01). In univariate logistic regression amongst all patients, chronic damage MRI scores, UWDRS part III scores and sNfL concentrations predicated early deterioration. In the neurological WD, only sNFL were a significant predictor. In bivariate logistic regression amongst all patients, sNfL remained the only significant predictor of deterioration when corrected for MRI scores.ConclusionsNfL concentrations are a promising biomarker of the risk of early neurological deterioration in WD.

ATP7B Genotype and Chronic Liver Disease Treatment Outcomes in Wilson Disease: Worse Survival With Loss-of-Function Variants

Background and AimsAlthough a good genotype-phenotype correlation has not been established in Wilson disease (WD), patients with loss-of-function (LOF) ATP7B variants demonstrate different clinical and biochemical characteristics. We aim to describe long-term treatment outcomes in the chronic liver disease (CLD) phenotype and evaluate an association with LOF variants. MethodsThis was a single-center retrospective review of WD patients with at least 1 variant in ATP7B. Demographic, biochemical, genetic, and clinical parameters were obtained. The composite clinical endpoint of liver transplantation or death was used for probands with CLD phenotype on chelators. ResultsOf 117 patients with hepatic WD: 71 had CLD, 27 had fulminant hepatic failure requiring urgent liver transplantation, and 19 were diagnosed through family screening. Median age at diagnosis was 13.1 (interquartile range, 9.7–17.6) years. In total, 91 variants in ATP7B were identified in the study population. At least 1 LOF variant was present in 60 (51.3%) patients. During median follow-up of 10.7 (interquartile range, 6.7–18.9) years, 10 (14.1%) of the probands with CLD reached the composite endpoint. There was a worse transplant-free survival for patients prescribed chelation therapy in patients with at least 1 LOF variant (P = .03). ConclusionsPatients with WD and CLD phenotype on chelators, who have at least 1 LOF variant in ATP7B, have a worse prognosis during long-term follow up. This subgroup of patients requires close monitoring for signs of progressive liver disease. Sequencing of ATP7B may be used in the diagnosis of WD, and in addition, it may provide useful prognostic information for patients with hepatic WD.

Brain MRI in the Decision for Liver Transplantation in Pediatric Neurological Wilson's Disease.

Neurological Wilson's disease (WD) presentation in the pediatric population is rare, and liver transplantation (LT) in these patients remains controversial. The aim of the present study was to assess the role of brain magnetic resonance imaging (MRI) in predicting reversion of brain lesions and neurological outcomes in pediatric WD patients after LT. Patients with confirmed WD (Leipzig score ≥4), disease onset in pediatric age (<18 years), neurological involvement, and submitted to LT were selected. Clinical records and pre- and post-LT brain MRI were evaluated. Six patients met the pre-defined inclusion criteria, one of whom died shortly after LT and was excluded. The indication for LT was end-stage liver disease in two patients and neurological worsening despite optimized treatment in three patients. After LT, the neurological picture progressively improved in all patients. Pre-LT brain MRI showed T1-weighted hyperintensities in four patients, which quickly resolved afterward. T2-weighted hyperintensities were observed in four patients before LT, completely resolving in one patient, stabilizing in two, and improving in one after LT. A direct correlation could not be found between clinical and neuroradiological improvement. Progressive clinical improvement was observed even in patients with irreversible brain MRI changes. Conversely, some patients with normal MRI had only slight neurological improvement. The pattern of T2-weighted hyperintensities after LT was unpredictable and did not correlate with neurological outcomes, suggesting that these changes may not entail irreversible clinical damage. Therefore, brain MRI does not seem to have prognostic value for assessing clinical response to LT.

Latest innovations in the treatment of Wilson's disease

Wilson's disease (WD), also called hepatolenticular degeneration, is an autosomal recessive copper dysfunction disorder that is among the few treatable neurogenetic disorders. The main goals for controlling WD are to lower copper intake and encourage copper removal. Medical treatments and low-copper diets are available, but many problems remain. For example, current treatments cannot fix copper metabolism and are unable to cross the blood–brain barrier. Furthermore, severe side effects have been experienced by many WD patients. Because lifelong therapy is required for this disease, adherence to medical therapy and best practices for monitoring and personalizing therapy continue to evolve; some of these issues are being addressed in ongoing studies. Additionally, novel chelating agents, gene therapies using adeno-associated viruses, and variant-specific therapies that may improve neurological outcomes are in development. Here, we review the latest treatment innovations that may play an essential role for WD patients in the future. • Wilson's disease (WD) is one of the few neurogenetic diseases that can be treated. • Current treatments neither can fix the copper metabolism nor cross the blood-brain barrier (BBB). • Besides, severe side effects have been experienced by many WD patients. • Novel chelating agents, gene therapy, and variant-specific treatments are in development.

Effect of oral zinc regimens on human hepatic copper content: a randomized intervention study

Zinc inhibits intestinal copper uptake, an effect utilized for treating Wilson’s disease (WD). We used copper-64 (64Cu) PET/CT to examine how much four weeks of treatment with different zinc regimens reduced the hepatic 64Cu content after oral 64Cu administration and test if alternative regimens were noninferior to the standard regimen of zinc acetate 50 mg × 3 daily. Forty healthy persons were randomized to four different zinc protocols. The WD standard treatment zinc acetate 50 mg × 3 reduced the hepatic 64Cu content from 26.9 ± 7.5% to 13.3 ± 5.6% of the administered 64Cu. Zinc gluconate 50 mg × 3 was noninferior (P = 0.02) (35.8 ± 9.0% to 17.4 ± 7.5%). Zinc acetate 150 mg × 1 (33.1 ± 9.9% to 17.4 ± 7.5%) and zinc gluconate 150 mg × 1 (28.1 ± 6.7% to 22.0 ± 6.7%) were less effective. These effects were intra- and inter-individually highly variable, and 14% had no effect of any zinc regimen, which may explain disparities in zinc treatment efficacy in WD patients.

The Maternal and Fetal Outcomes of Pregnancy in Wilson's Disease: A Systematic Literature Review and Meta-Analysis.

Wilson’s disease (WD) is a rare, treatable genetic disorder with multi-organ symptoms related mainly to copper accumulation. Most patients become aware of the disease as young adults, thus knowledge on fertility, pregnancy course and outcome is very important both for patients and physicians. The aim of this study was to perform a systematic review and meta-analysis of pregnancy outcomes in women with WD. This systematic literature review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were identified by searching the PubMed database (up to 12 January 2022) and by screening reference lists. We found 49 publications, including 13 retrospective studies and 36 series and case reports on pregnancy outcomes in WD patients. In total, descriptions of 449 pregnant women with 822 pregnancies were retrieved. Successful deliveries were achieved in 78.3% (644/822) of all pregnancies. Spontaneous abortions were observed in 21.7% (178/822) of pregnancies, more frequently in patients who were untreated 68.6% (96/140). Analyzing maternal outcome, 2.2% (18/822) of pregnancies were associated with the aggravation of neurological symptoms. Symptoms of hepatic deterioration were observed in 4.6% (38/822) of cases. These were usually transient and recovered after pregnancy; however, death due to liver failure was observed in 0.2% (2/822) of cases. Birth defects occurred in 4.7% (39/822) of pregnancies. The available meta-analysis showed statistically significant positive associations between anti-copper treatment and pregnancy outcome. Our results document the significance of anti-copper treatment as the main factor leading to successful pregnancy, as well as positive outcomes for women with WD.

Cardiac involvement in Wilson's disease: a retrospective cohort study.

Wilson's disease (WD) is an inherited disorder with perturbations in copper metabolism and can cause multiorgan damage. This study aims to explore cardiac findings mainly based on electrocardiography (ECG) in WD patients. We retrospectively enrolled adult patients who were diagnosed with WD between January 2011 and December 2020. Demographic and clinical data were collected and reevaluated. A total of 126 patients were included. There were 71 men and 55 women. The mean age was 27.2 years. Ninety-nine had hepatic presentation as the initial symptom and 27 had neuropsychiatric presentation as the initial symptom. Thirty-seven patients (29.4%) had cardiac manifestations. Of these patients, nine presented apparent cardiac symptoms (three with discontinuous chest tightness, three with dizziness, two with palpitation and one with atypical chest pain) and 28 had asymptomatic electrocardiography (ECG) abnormalities. Among the nine patients, four had second- or third-degree atrioventricular block, three had ST-segment change and two had ventricular tachycardia. ECG abnormalities in the 28 patients included increase in the width of the QRS complex in 8, atrial premature beats in 8, T-wave inversion in 5, P-wave inversion in 2, sinus bradycardia in 2, ST-segment change in 2, and coexistence of sinus bradycardia and T-wave inversion in 1. No statistical difference (P = 0.32) existed in the occurrence of ECG abnormalities between patients with hepatic presentation (27/99) and those with neuropsychiatric presentation (10/27). Cardiac involvement is not rare in adult WD patients. We suggest that cardiac evaluation should be routinely performed in the population.

Lesions in White Matter in Wilson's Disease and Correlation with Clinical Characteristics.

Neuroimaging studies in Wilson's disease (WD) have identified various alterations in white matter (WM) microstructural organization. However, it remains unclear whether these alterations are localized to specific regions of fiber tracts, and what diagnostic value they might have. The purpose of this study is to explore the spatial profile of WM abnormalities along defined fiber tracts in WD and its clinical relevance. Ninety-nine patients with WD (62 men and 37 women) and 91 age- and sex-matched controls (59 men and 32 women) were recruited to take part in experiments of diffusion-weighted imaging with 64 gradient vectors. The data were calculated by FMRIB Software Library (FSL) software and Automated Fiber Quantification (AFQ) software. After registration, patient groups and normal groups were compared by Mann-Whitney U test analysis. Compared with the controls, the patients with WD showed widespread fractional anisotropy reduction and mean diffusivity, radial diffusivity elevation of identified fiber tracts. Significant correlations between diffusion tensor imaging (DTI) parameters and the neurological Unified Wilson's Disease Rating Scale (UWDRS-N), serum ceruloplasmin, and 24-h urinary copper excretion were found. The present study has provided evidence that the metrics of DTI could be utilized as a potential biomarker of neuropathological symptoms in WD. Damage to the microstructure of callosum forceps and corticospinal tract may be involved in the pathophysiological process of neurological symptoms in WD patients, such as gait and balance disturbances, involuntary movements, dysphagia, and autonomic dysfunction.

Use of the bibliometric in rare diseases: taking Wilson disease personally

BackgroundBibliometric have been widely applied to the evaluation of academic productivity. However, those of individuals or institutions on a specific disease have not been explored. The aim of the present study is to conduct a bibliometric analysis of particular rare disease and investigate whether those doctors and hospitals with higher index screened by this method specialize in this disease.MethodsA representative rare disease, Wilson disease (WD), was searched on Clarivate Analytics’ Web of Science and Elsevier’s Scopus, which was published in English between 1 January 2001 and 31 December 2020. Clinical authors and medical institutions with the most papers were screened, and their total number of publications and citations, h-index and g-index were computed and then ranked by h-index.ResultsA total of 6856 and 6193 papers and 200 and 160 authors were got from WoS and Scopus, respectively. Scopus provided 160 institutions. The above bibliometric indices were calculated in 100 researchers and 80 institutions, and top 30 authors (Top-30a) and top 20 institutions (Top-20i) of them based on the h-index were listed in the tables. Top-30a came from seven specialties and 13 countries whose median (interquartile range) h-index was 14 (12–19.5) (range 10–28) which was located between associate and full professors in some other disciplines. Top-20i was distributed in 13 countries whose mean ± standard deviation of the h-index was 15 ± 4.9 (range 10–27).ConclusionsThe related specialists and medical institutions of WD screened by specific disease bibliometric analysis are eminent and credible and benefit WD patients to obtain reliable medical treatment. This model may be suitable for other rare diseases.

Low Copper Diet-A Therapeutic Option for Wilson Disease?

Wilson’s disease (WD) is an autosomal recessive inherited disease in which a pathological storage of copper in various organs is the mean pathophysiological mechanism. The therapy consists of drug therapy with chelating agents or zinc. For patients, nutrition is always an important issue. The aim of this review was to determine whether there are clear recommendations for a low copper diet for WD patients, or whether the essential trace element zinc plays a role? We were able to show that some of the foods with high copper content would have to be consumed in such large quantities that this is regularly not the case. Furthermore, there are also different absorption rates depending on the copper content. A lower copper intake only prevents the re-accumulation of copper. In summary, consistent adherence to drug therapy is more important than a strict diet. Only two foods should be consistently avoided: Liver and Shellfish.

Autoantibodies in Wilson disease: Impact on clinical course.

Symptoms of Wilson disease (WD) vary and additional factors such as autoimmunity may play an important role in WD pathogenesis. The presence of antinuclear antibodies (ANA), anti‐neutrophil cytoplasmic antibodies, neuronal surface antibodies, and onconeural antibodies in WD was investigated using standardized indirect immunofluorescence assays and Western Blot analysis. The presence of all studied autoantibodies was higher in WD patients in comparison to healthy subjects, but there was no statistically significant difference in autoantibodies frequency according to disease manifestation. D‐penicillamine treatment was associated with a higher presence of ANA than zinc sulfate but without an increase in autoimmune diseases rate.