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Wilson's disease (WD) is an inherited autosomal recessive disorder of copper metabolism, that affects the liver, the brain, and the musculoskeletal system. The symptoms, clinical course, and outcome of WD are highly variable. The main features—the hepatic and the neurologic forms—can be distinguished, but many patients present with a mixture of both. Diagnosis is based on the combination of clinical signs, biochemical features, histologic findings, and molecular analysis of ATP7B gene, when available. The diagnosis of WD is suggested biochemically by the association of increase serum transaminase concentrations, low serum ceruloplasmin, and high urinary copper concentration. The relative lack of sensitive and specific criteria for the rapid diagnosis of WD has made it difficult to diagnose. It is imperative to consider the differential diagnoses including MEDNIK disease, CDG, and MDRIII deficiency, where copper levels are altered. Making the correct diagnosis is imperative since there are no beneficial effects to chelation in MDRIII, CDG, or other non-WD conditions. These diagnostic difficulties illustrate the importance of metabolic screening and molecular genetics tests in the exact diagnosis of these disorders. Untreated, WD invariably leads to death from liver disease or severe neurological disability, and early and rapid diagnosis remains paramount for optimal patient management. [ABSTRACT FROM AUTHOR]

Programmable and modular systems capable of orthogonal genomic and transcriptomic perturbations are crucial for biological research and treating human genetic diseases. Here, we present the minimal versatile genetic perturbation technology (mvGPT), a flexible toolkit designed for simultaneous and orthogonal gene editing, activation, and repression in human cells. The mvGPT combines an engineered compact prime editor (PE), a fusion activator MS2–p65–HSF1 (MPH), and a drive-and-process multiplex array that produces RNAs tailored to different types of genetic perturbation. mvGPT can precisely edit human genome via PE coupled with a prime editing guide RNA and a nicking guide RNA, activate endogenous gene expression using PE with a truncated single guide RNA containing MPH-recruiting MS2 aptamers, and silence endogenous gene expression via RNA interference with a short-hairpin RNA. We showcase the versatility of mvGPT by simultaneously correcting a c.3207C>A mutation in the ATP7B gene linked to Wilson's disease, upregulating the PDX1 gene expression to potentially treat Type I diabetes, and suppressing the TTR gene to manage transthyretin amyloidosis. In addition to plasmid delivery, we successfully utilize various methods to deliver the mvGPT payload, demonstrating its potential for future in vivo applications. Molecular tools enabling precise DNA mutations and targeted modulation of gene expression have significant potential in medicine and biology. Here, the authors develop a compact system for simultaneous and independent gene editing, activation, and repression in mammalian cells. [ABSTRACT FROM AUTHOR]

Trientine tetrahydrochloride (TETA-4HCl, Cuvrior®) is a copper chelating agent with the active moiety triethylenetetramine (trientine), developed by Orphalan, Inc. to address the unmet needs in the treatment of Wilson disease. The journey from bench to bedside builds upon the documented safety profile of trientine hydrochloride capsules developed initially to meet the needs of individuals intolerant to d-penicillamine (DPA). Trientine hydrochloride capsules are inherently unstable requiring strict cold chain storage conditions from production, transportation, and use at home by the patient. Trientine tetrahydrochloride has a distinctive, patent-protected unique polymorphic form, which permits the production at scale of film-coated scored tablets deemed room temperature stable for 36 months. Trientine tetrahydrochloride is supported by a well-characterized pharmacodynamic, pharmacokinetic, and metabolic profile demonstrating reliable and predictable dose linearity and dose proportionality kinetics. Trientine tetrahydrochloride is the only trientine formulation that has been compared with DPA in a prospective randomized clinical trial, demonstrating non-inferiority to DPA in adults with stable Wilson disease. On 28 April, 2022, the US Food and Drug Administration approved TETA-4HCl for use in adult patients with Wilson disease who are de-coppered and tolerant to DPA. Health authorities in multiple countries worldwide have approved TETA-4HCl for the treatment of adults and children aged 5 years or more who are intolerant to DPA including the European Union, UK, Saudi Arabia, Switzerland, Colombia, Australia, New Zealand, and China. This article aims to provide a comprehensive narrative review of the key milestones in the development of TETA-4HCl. [ABSTRACT FROM AUTHOR]

This article discusses a case study of a patient with cirrhosis who presented with weakness, dysarthria, insomnia, and depression. Initially, his cirrhosis was attributed to alcohol use, but further investigation led to the diagnosis of Wilson's disease, a rare genetic disorder that affects copper metabolism. The article highlights the challenges of diagnosing Wilson's disease, which can mimic other diseases, and emphasizes the importance of obtaining a detailed family history. It also discusses the barriers to diagnosis and care that can occur in underserved populations, such as language barriers and low health literacy. Early identification and treatment of Wilson's disease can reverse symptoms and improve outcomes. [Extracted from the article]

Background: Wilson's disease (WD) is a rare condition resulting from autosomal recessive mutations in ATP7B, a copper transporter, manifesting with hepatic, neurological, and psychiatric symptoms. Timely diagnosis and appropriate treatment yield a positive prognosis, while delayed identification and/or insufficient therapy lead to a poor outcome. Our aim was to establish a prognostic method for WD by characterising biomarkers based on circulating microRNAs. Methods: We conducted investigations across three cohorts: discovery, validation (comprising unrelated patients), and follow-up (revisiting the discovery cohort 3 years later). All groups were compared to age- and gender-matched controls. Plasma microRNAs were analysed via RNA sequencing in the discovery cohort and subsequently validated using quantitative PCR in all three cohorts. To assess disease progression, we examined the microRNA profile in Atp7b−/− mice, analysing serum samples from 6 to 44 weeks of age and liver samples at three time points: 20, 30, and 40 weeks of age. Results: In patients, elevated levels of the signature microRNAs (miR-122-5p, miR-192-5p, and miR-885-5p) correlated with serum activities of aspartate transaminase, alanine aminotransferase and gamma-glutamyl transferase. In Atp7b−/− mice, levels of miR-122-5p and miR-192-5p (miR-885-5p lacking a murine orthologue) increased from 12 weeks of age in serum, while exhibiting fluctuations in the liver, possibly attributable to hepatocyte regenerative capacity post-injury and the release of hepatic microRNAs into the bloodstream. Conclusions: The upregulation of the signature miR-122-5p, miR-192-5p, and miR-885-5p in patients and their correlation with liver disease progression in WD mice support their potential as biomarkers of WD. [ABSTRACT FROM AUTHOR]

Cuproptosis, a newly characterized form of regulated cell death driven by copper accumulation, has emerged as a significant mechanism underlying various non-cancerous diseases. This review delves into the complex interplay between copper metabolism and the pathogenesis of conditions such as Wilson's disease (WD), neurodegenerative disorders, and cardiovascular pathologies. We examine the molecular mechanisms by which copper dysregulation induces cuproptosis, highlighting the pivotal roles of key copper transporters and enzymes. Additionally, we evaluate the therapeutic potential of copper chelation strategies, which have shown promise in experimental models by mitigating copper-induced cellular damage and restoring physiological homeostasis. Through a comprehensive synthesis of recent advancements and current knowledge, this review underscores the necessity of further research to translate these findings into clinical applications. The ultimate goal is to harness the therapeutic potential of targeting cuproptosis, thereby improving disease management and patient outcomes in non-cancerous conditions associated with copper dysregulation. [ABSTRACT FROM AUTHOR]

Hepatolenticular degeneration (HLD), also known as Wilson's disease (WD), is a rare autosomal recessive disorder regarding copper metabolism. Whether gut microbiota imbalance is involved in developing HLD remains unknown. A comprehensive 16S rRNA amplicon sequencing, metagenomic sequencing, and metabonomic analysis were undertaken in patients with WD to analyze the composition and function profiles of gut microbiota in patients with WD. The data demonstrated differences in gut microbiota and metabolic pathways between WD patients and normal individuals, significantly decreasing bacterial richness and diversity. The levels of Selenomonaceae and Megamonas in WD patients are significantly higher than those in healthy individuals. The relative abundances of Roseburia inulinivorans in patients with WD are lower than in healthy individuals. Compared with healthy people, the level of metabolites in patients with WD is abnormal. Leucylproline, 5-Phenylvaleric Acid and N-Desmethylclobazam, which have nutritional and protective effects, are significantly reduced fecal metabolites in patients with WD. D-Gluconic acid, which can chelate metal ions, may be a potential treatment for WD. The positive correlation it demonstrates with Alistipes indistinctus and Prevotella stercora indicates potential bacteria able to treat WD. These metabolites are mainly related to the biosynthesis of antibiotics, alpha-linolenic acid metabolism, one carbon pool by folate, nicotinate and nicotinamide metabolism. In conclusion, the data from this study elucidate novel mechanisms describing how abnormal gut miccrobiota contribute to the pathogenesis of WD and outlines new molecules for the treatment of WD. [ABSTRACT FROM AUTHOR]

Background: Wilson's disease is an inherited disease characterized by impaired copper metabolism that causes damage to many organs, including the brain. Patients having neurological involvement usually present with varied neuropsychiatric symptoms. Magnetic resonance imaging (MRI) Brain plays an indispensable role in identifying the structural involvement in these patients, aiding in early accurate diagnosis and timely management. Typically, basal ganglia, thalami and brainstem are involved, with bright claustrum sign, face of giant panda sign and miniature panda signs on MRI. Conclusions: Having knowledge about the commonly encountered and known MRI brain findings in Wilson's disease are essential in aiding accurate diagnosis and initiating early management. However, identifying the Atypical MRI brain characteristics is all the more imperative and should be considered in patients with prolonged or severe disease or in patients with rapid clinical progression and in patients showing poor response to treatment. [ABSTRACT FROM AUTHOR]

Introduction: Wilson's disease (WD) is associated with a variety of movement disorders and progressive neurological dysfunction. The aim of this study was to correlate baseline brain magnetic resonance imaging (MRI) features with clinical phenotype and long-term outcomes in chronically treated WD patients. Methods: Patients were retrospectively selected from an institutional database. Two experienced neuroradiologists reviewed baseline brain MRI. Functional assessment was performed using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) scale, and disease severity was classified using the Global Assessment Scale for Wilson's Disease (GASWD). Results: Of 27 patients selected, 14 were female (51.9%), with a mean (standard deviation [SD]) age at onset of 19.5 (7.1) years. Neurological symptoms developed in 22 patients (81.5%), with hyperkinetic symptoms being the most common (70.4%). Baseline brain MRI showed abnormal findings in 18 cases (66.7%), including T2 hyperintensities in 59.3% and atrophy in 29.6%. After a mean (SD) follow-up of 20.9 (11.0) years, WD patients had a mean score of 19.2 (10.2) on WHODAS 2.0 and 6.4 (5.7) on GASWD. The presence of hyperkinetic symptoms correlated with putaminal T2 hyperintensities (p = 0.003), putaminal T2 hypointensities (p = 0.009), and mesencephalic T2 hyperintensities (p = 0.009). Increased functional disability was associated with brain atrophy (p = 0.007), diffusion abnormalities (p = 0.013), and burden of T2 hyperintensities (p = 0.002). A stepwise regression model identified atrophy as a predictor of increased WHODAS 2.0 (p = 0.023) and GASWD (p = 0.007) scores. Conclusions: Atrophy and, to a lesser extent, deep T2 hyperintensity are associated with functional disability and disease severity in long-term follow-up of WD patients. [ABSTRACT FROM AUTHOR]

Excessive Cu2+ intake can cause neurological disorders (e.g. Wilson's disease) and adversely affect the gastrointestinal, liver, and kidney organs. The presence of Cu2+ is strongly linked to the emergence and progression of Wilson's disease (WD), and accurately measuring the amount of copper is a crucial step in diagnosing WD at an early stage in a clinical setting. In this work, CQDs were fabricated through a facile technique as a novel fluorescence-based sensing platform for detecting Cu(II) in aqueous solutions, and in the serum samples of healthy and affected individuals by WD. The CQDs interact with Cu(II) ions to produce Turn-on and Turn-off states at nano-molar and micro-molar levels, respectively, with LODs of 0.001 µM and 1 µM. In fact, the Cu2+ ions can act like a bridge between two CQDs by which the charge and electron transfer between the CQDs may increase, possibly can have significant effects on the spectroscopic features of the CQDs. To the best of our knowledge, this is the first reported research that can detect Cu(II) at low levels using two different complexation states, with promising results in testing serum. The potential of the sensor to detect Cu(II) was tested on serum samples from healthy and affected individuals by WD, and compared to results obtained by ICP-OES. Astonishingly, the results showed an excellent correlation between the measured Cu(II) levels using the proposed technique and ICP-OES, indicating the high potential of the fluorimetric CQD-based probe for Cu(II) detection. The accuracy, sensitivity, selectivity, high precision, accuracy, and applicability of the probe toward Cu(II) ions make it a potential diagnostic tool for Wilson's disease in a clinical setting. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to examine the volumes of thalamic nuclei and the intrinsic thalamic network in patients with Wilson's disease (WDs), and to explore the correlation between these volumes and the severity of neurological symptoms. Methods: A total of 61 WDs and 33 healthy controls (HCs) were included in the study. The volumes of 25 bilateral thalamic nuclei were measured using structural imaging analysis with Freesurfer, and the intrinsic thalamic network was evaluated through structural covariance network (SCN) analysis. Results: The results indicated that multiple thalamic nuclei were smaller in WDs compared to HCs, including mediodorsal medial magnocellular (MDm), anterior ventral (AV), central median (CeM), centromedian (CM), lateral geniculate (LGN), limitans-suprageniculate (L-Sg), reuniens-medial ventral (MV), paracentral (Pc), parafascicular (Pf), paratenial (Pt), pulvinar anterior (PuA), pulvinar inferior (PuI), pulvinar medial (PuM), ventral anterior (VA), ventral anterior magnocellular (VAmc), ventral lateral anterior (VLa), ventral lateral posterior (VLp), ventromedial (VM), ventral posterolateral (VPL), and right middle dorsal intralaminar (MDI). The study also found a negative correlation between the UWDRS scores and the volume of the right MDm. The intrinsic thalamic network analysis showed abnormal topological properties in WDs, including increased mean local efficiency, modularity, normalized clustering coefficient, small-world index, and characteristic path length, and a corresponding decrease in mean node betweenness centrality. WDs with cerebral involvement had a lower modularity compared to HCs. Conclusions: The findings suggest that the majority of thalamic nuclei in WDs exhibit significant volume reduction, and the atrophy of the right MDm is closely related to the severity of neurological symptoms. The intrinsic thalamic network in WDs demonstrated abnormal topological properties, indicating a close relationship with neurological impairment. [ABSTRACT FROM AUTHOR]

Introduction: Rapunzel syndrome is a very rare form of trichobezoar. It is strongly linked to psychiatric conditions; trichotillomania and trichophagia. These conditions in the pediatric population point to the presence of childhood stressors like child neglect, abuse, etc. This case report highlights that child neglect may be an underlying contributing factor in selected cases of Rapunzel syndrome. Hence, a multidisciplinary approach should be sought in all cases of Rapunzel syndrome, catering to the emotional and psychological needs of the pediatric population. Case presentation: A 7-year-old girl from a low socioeconomic background presented with periorbital and facial swelling, abdominal distension, and pallor. On physical examination, she showed bilateral pitting edema and a distended abdomen with poor overall hygienic condition. Her family history was positive for Wilson's disease. Lab investigations highlighted iron deficiency anemia (Hb 8.2 g/dL), with normal liver function. Ultrasound demonstrated ascites, liver changes, and pleural effusion. The work-up for Wilson's disease was unremarkable. During the hospital course, her abdominal distention lessened; a non-tender epigastric mass (4 × 5 cm) was thus discovered. An abdominal X-ray revealed an entangled mass outlining the gastric shadow. Her parents also revealed a history of trichophagia. Suspecting a large trichobezoar, a laparotomy was performed. After the midline incision, the stomach was opened anteriorly between stay sutures along the curvature. It delivered a large trichobezoar, 65 cm in length extending up to the proximal jejunum. Rapunzel syndrome diagnosis was finally established. Conclusion: This unique presentation emphasizes the need to consider this rare etiology, even with unusual clinical histories especially with a history of child neglect, while collaborative surgical interventions facilitate successful outcomes. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) are a recently discovered group of non-coding RNAs that play a crucial role in the regulation of various human diseases, especially in the study of nervous system diseases which has garnered significant attention. However, there is limited knowledge on the identification and function of lncRNAs in hepatolenticular degeneration (HLD). The objective of this study was to identify novel lncRNAs and determine their involvement in the networks associated with HLD. We conducted a comprehensive analysis of RNA sequencing (RNA-seq) data, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and computational biology to identify novel lncRNAs and explore their potential mechanisms in HLD. We identified 212 differently expressed lncRNAs, with 98 upregulated and 114 downregulated. Additionally, 32 differently expressed mRNAs were found, with 15 upregulated and 17 downregulated. We obtained a total of 1131 pairs of co-expressed lncRNAs and mRNAs by Pearson correlation test and prediction and annotation of the lncRNA-targeted miRNA-mRNA network. The differential lncRNAs identified in this study were found to be involved in various biological functions and signaling pathways. These include translational initiation, motor learning, locomotors behavior, dioxygenase activity, integral component of postsynaptic membrane, neuroactive ligand-receptor interaction, nuclear factor-kappa B (NF-κB) signaling pathway, cholinergic synapse, sphingolipid signaling pathway, and Parkinson's disease signaling pathway, as revealed by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Six lncRNAs, including XR_001782921.1 (P < 0.01), XR_ 001780581.1 (P < 0.01), ENSMUST_00000207119 (P < 0.01), XR_865512.2 (P < 0.01), TCONS_00005916 (P < 0.01), and TCONS_00020683 (P < 0.01), showed significant differences in expression levels between the model group and normal group by RT-qPCR. Among these, four lncRNAs (TCONS_00020683, XR_865512.2, XR_001780581.1, and ENSMUST00000207119) displayed a high degree of conservation. This study provides a unique perspective for the pathogenesis and therapy of HLD by constructing the lncRNA-miRNA-mRNA network. This insight provides a foundation for future exploration in this field. [ABSTRACT FROM AUTHOR]

Trientine or (N,N´-bis(2-aminoethyl)-1,2-ethanediamine (TETA) is a copper chelator and used in Wilson's disease, is aliphatic amine that does not have UV absorbing groups. In this study, the modified silver nanoparticles (AgNPs) by sodium lauryl sulfate have been used to develop an analytical method for quantification of TETA. Different concentrations of TETA were added into a particular concentration of AgNPs and absorbance of each sample was measured at 397 nm under the optimal conditions which include pH, time, salt and AgNPs volume. It was optimized by a design of experiments using response surface methodology. Then, the calibration curve was obtained based on the concentrations of TETA solution versus decrease in the absorbance of AgNPs. Selectivity of the developed method was performed in plasma and presence of common cations i.e. copper, zinc and ferrous. Under optimum conditions, linear range of this method was between 10 and 40 ng.mL− 1 with correlation coefficient (R2) of 0.996 with limit of detection and quantification of 3 ng.mL− 1 and 10 ng.mL− 1, respectively. Selectivity of established method in presence of cations eliminated by diluting because of high sensitivity of the established analytical techniques based on AgNPs. This method is suitable and low costing for quantification of TETA and does not require high equipment. [ABSTRACT FROM AUTHOR]

Simple, portable, and low-cost paper-based sensors are alternative devices that have the potential to replace high-cost sensing technologies. The compatibility of the paper base biosensors for both chemical and biochemical accentuates its feasibility for application in clinical diagnosis, environmental monitoring, and food quality monitoring. High concentration of copper in blood serum and urine is associated with diseases like liver diseases, carcinomas, acute and chronic infections, rheumatoid arthritis, etc. Detection of copper concentration can give an early sign of Alzheimer disease. Apart from that genetic Wilson's disease can be detected by evaluating the concentration of copper in the urine. In view of the above advantages, a novel and the highly sensitive paper-based sensor has been designed for the selective detection of Cu2+ ions. The fast and highly sensitive chemiresistive multi-dye system sensor can detect Cu2+ ions selectively in as low as 2.23 ppm concentration. Least interference has been observed for counter ion in the detection of Cu2+. Copper chloride, nitrate, and acetate were used to validate the detection process. This assay provides a very high selectivity of Cu2+ ion over other metal cations such as Na+, Mg2+, Ca2+, etc. The easy preparation and high stability of dye solutions, easy functionalization of the paper-based sensors, high selectivity over other cations, low interference of counter anion, and significantly low detection limit of 2.23 ppm make it an effective Cu2+ ion sensor for real-time application in near future. [ABSTRACT FROM AUTHOR]

The comprehensive review by Lafhal and Fdil provides overview of the pathophysiology, clinical features, and different diagnostic strategies for Wilson's disease (WD), a rare and serious hereditary disorder of copper metabolism. The variable clinical manifestations of WD and the lack of a single definitive test presents significant diagnostic challenges. [ABSTRACT FROM AUTHOR]

Introduction: Neurological deterioration, soon after anti-copper treatment initiation, is problematic in the management of Wilson's disease (WD) and yet reports in the literature are limited. The aim of our study was to systematically assess the data according to early neurological deteriorations in WD, its outcome and risk factors. Methods: Using PRISMA guidelines, a systematic review of available data on early neurological deteriorations was performed by searching the PubMed database and reference lists. Random effects meta-analytic models summarized cases of neurological deterioration by disease phenotype. Results: Across the 32 included articles, 217 cases of early neurological deterioration occurred in 1512 WD patients (frequency 14.3%), most commonly in patients with neurological WD (21.8%; 167/763), rarely in hepatic disease (1.3%; 5/377), and with no cases among asymptomatic individuals. Most neurological deterioration occurred in patients treated with d-penicillamine (70.5%; 153/217), trientine (14.2%; 31/217) or zinc salts (6.9%; 15/217); the data did not allow to determine if that reflects how often treatments were chosen as first line therapy or if the risk of deterioration differed with therapy. Symptoms completely resolved in 24.2% of patients (31/128), resolved partially in 27.3% (35/128), did not improve in 39.8% (51/128), with 11 patients lost to follow-up. Conclusions: Given its occurrence in up to 21.8% of patients with neurological WD in this meta-analysis of small studies, there is a need for further investigations to distinguish the natural time course of WD from treatment-related early deterioration and to develop a standard definition for treatment-induced effects. [ABSTRACT FROM AUTHOR]

Labile copper(II) ions (Cu2+) in serum are considered to be readily available for cellular uptake and to constitute the biologically active Cu2+ species in the blood. It might also be suitable to reflect copper dyshomeostasis during diseases such as Wilson's disease (WD) or neurological disorders. So far, no direct quantification method has been described to determine this small Cu2+ subset. This study introduces a fluorometric high throughput assay using the novel Cu2+ binding fluoresceine-peptide sensor FP4 (Kd of the Cu2+-FP4-complex 0.38 pM) to determine labile Cu2+ in human and rat serum. Using 96 human serum samples, labile Cu2+was measured to be 0.14 ± 0.05 pM, showing no correlation with age or other serum trace elements. No sex-specific differences in labile Cu2+ concentrations were noted, in contrast to the total copper levels in serum. Analysis of the effect of drug therapy on labile Cu2+ in the sera of 19 patients with WD showed a significant decrease in labile Cu2+ following copper chelation therapy, suggesting that labile Cu2+ may be a specific marker of disease status and that the assay could be suitable for monitoring treatment progress. [ABSTRACT FROM AUTHOR]

Purpose: Several outbreaks of acute hepatitis of unknown etiology (AHUE) in children were reported in 2022 in many countries, with adenovirus identified as the etiological agent in most of them. We aimed to evaluate the characteristics and outcomes of AHUE cases in Egypt. Methodology: Hospitalized patients with acute hepatitis were included in the study. Drug-induced, alcoholic hepatitis, autoimmune hepatitis, and Wilson's disease were identified either by medical history or by routine laboratory diagnosis. Molecular and serological approaches were used to investigate common viral causes of hepatitis, such as hepatitis A–E viruses, cytomegalovirus, Epstein–Barr virus, herpes simplex viruses (HSV1/2), adenovirus, parvovirus B19, and coxsackie virus. Results: A total of 42 patients were recruited and divided into two groups: 24 cases of unknown hepatitis after excluding the common causes and 18 cases of known hepatitis. About two-thirds of the patients were male (61.9%), and the mean age was 34.55 ± 16.27 years. Jaundice, dark urine, abdominal pain and diarrhea were recorded at a higher incidence in group 1, while jaundice and fever were frequent in group 2. Fulminant hepatitis occurred in 28.6% of the cases, but the two groups did not differ significantly in terms of patient outcome, duration of hospitalization, ascites, and development of fulminant hepatitis. Adenovirus was detected in five cases (20.8%) in group 1, and one case co-infecting with hepatitis E virus in group 2. Herpes simplex virus 1/2, coxsackie virus, and parvovirus B19 were not detected in any case, while etiologies of 75% of the cases were still not confirmed. One out of the six adenovirus-infected patients died. The outcome significantly correlated with the severity of the liver disease. Conclusion: This is the first report describing etiologies and characteristics of AHUE cases in Egypt, and interestingly, adenovirus was detected in adults. Further studies are required to determine the prevalence of this newly emerging viral hepatitis pathogens. [ABSTRACT FROM AUTHOR]

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Background: Chronic hepatitis C (HCV) and B viruses (HBV) represent the commonest global causes of liver cirrhosis. Other etiologies of non-viral cirrhosis such as autoimmune, metabolic, vascular, or biliary diseases are underestimated. The study aimed to identify causes, clinicoepidemiological characteristics, and outcome of non-B non-C liver cirrhosis. This Egyptian multicenter study recruited patients with liver cirrhosis excluding HCV and HBV. Clinical evaluation and the mortality were recorded. Laboratory, radiological, and histopathological assessment to diagnose the etiology was performed. Results: One hundred eighty-eight patients were included: 54.3% were males. Autoimmune hepatitis (AIH) was the most common cause of cirrhosis (28.2%), followed by Budd-Chiari syndrome (BCS) in 25%, and cryptogenic in 23.9%. Metabolic causes such as Wilson's disease, non-alcoholic steatohepatitis (NASH), and hemochromatosis were reported in 7.4%, 3.2%, and 1.1%, respectively. Biliary and cardiac cirrhosis were less frequent. Older age was prevalent in hemochromatosis (67.5 ± 17.7 years) and NASH (60.7 ± 11), while young age in Wilson's disease (29.5 ± 14.8) and secondary biliary cirrhosis (14.8 ± 4.8). Rural residence was common (60.6%). Mortality was reported in BCS (40.4%), cryptogenic (28.9%), cardiac (25%), Wilson's disease (21.4%), AIH (17%), and NASH (16.7%). Hepatocellular carcinoma complicated 10.6% of cases. A significantly high percentage of patients had decompensated cirrhosis. Child–Pugh class and rural residence were significant predictors of mortality. Conclusion: This first report on non-B non-C cirrhosis in Egypt revealed a high prevalence of AIH, BCS, and cryptogenic cirrhosis. Advanced Child class and rural residence were the predictors of mortality. [ABSTRACT FROM AUTHOR]

Background: A substantial proportion of Wilson's disease (WD) patients exhibit residual neurological symptoms. Data on the prognostic value of initial clinical features and treatment choices in WD patients compliant to the therapy is relatively sparse. Aim: The aim of the present study was to identify predictors of the long-term outcome of patients with WD with good treatment adherence. Methods: Forty patients with neurological form of WD were evaluated before the de-coppering treatment initiation (based on the medical records) and after mean 15.25 ± 11.24 years of the stable treatment. Severity of neurological symptoms were assessed with a tier two of Global Assessment Scale (GAS) for Wilson's Disease. Results: The most frequent symptoms prior to treatment initiation were dysarthria (90%), tremor (90%), clumsiness (67.5%), depression (67.5%), and gait disturbance (62.5%). Significant decrease in the frequency of dysarthria, clumsiness, tremor, gait disturbance, postural instability and an improvement in school/work performance were observed after the long-term treatment, while frequency of dysphagia, drooling, bradykinesia and rigidity, dystonic and choreatic features did not change. Overall symptom severity decreased over time. Presence of dystonia before treatment initiation was the only identified predictor of worse residual GAS score. Greater severity of residual dystonia was associated with female gender and longer disease duration. Conclusion: Although patients with neurological form of WD compliant to de-coppering treatment had favorable disease outcome, a significant burden of residual neurological symptoms was observed after the long-term follow-up. Dystonia at disease onset was the only identified predictor of the worse long-term outcome. [ABSTRACT FROM AUTHOR]

Selenium homeostasis depends on hepatic biosynthesis of selenoprotein P (SELENOP) and SELENOP-mediated transport from the liver to e.g. the brain. In addition, the liver maintains copper homeostasis. Selenium and copper metabolism are inversely regulated, as increasing copper and decreasing selenium levels are observed in blood during aging and inflammation. Here we show that copper treatment increased intracellular selenium and SELENOP in hepatocytes and decreased extracellular SELENOP levels. Hepatic accumulation of copper is a characteristic of Wilson's disease. Accordingly, SELENOP levels were low in serum of Wilson's disease patients and Wilson's rats. Mechanistically, drugs targeting protein transport in the Golgi complex mimicked some of the effects observed, indicating a disrupting effect of excessive copper on intracellular SELENOP transport resulting in its accumulation in the late Golgi. Our data suggest that hepatic copper levels determine SELENOP release from the liver and may affect selenium transport to peripheral organs such as the brain. Selenium and copper are two essential trace elements whose homeostasis and distribution is regulated by hepatic release of selenoprotein P (SELENOP) and ceruloplasmin, respectively. Here, the authors show that excessive copper results in hepatic SELENOP accumulation in the trans Golgi which might limit the selenium transport to peripheral organs. [ABSTRACT FROM AUTHOR]

Wilson's disease (WD) is an autosomal recessive disorder with a genetic basis. The predominant non-motor symptom of WD is cognitive dysfunction, although the specific genetic regulatory mechanism remains unclear. Tx-J mice, with an 82% sequence homology of the ATP7B gene to the human gene, are considered the most suitable model for WD. This study employs deep sequencing to investigate the differences in RNA transcript profiles, both coding and non-coding, as well as the functional characteristics of the regulatory network involved in WD cognitive impairment. The cognitive function of tx-J mice was evaluated using the Water Maze Test (WMT). Long non-coding RNA (lncRNA), circular RNA (circRNA), and messenger RNA (mRNA) profiles were analyzed in the hippocampal tissue of tx-J mice to identify differentially expressed RNAs (DE-RNAs). Subsequently, the DE-RNAs were used to construct protein–protein interaction (PPI) networks, as well as DE-circRNAs and lncRNAs-associated competing endogenous RNA (ceRNA) expression networks, and coding-noncoding co-expression (CNC) networks. To elucidate their biological functions and pathways, the PPI and ceRNA networks were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. A total of 361 differentially expressed mRNAs (DE-mRNAs), comprising 193 up-regulated and 168 down-regulated mRNAs, 2627 differentially expressed long non-coding RNAs (DE-lncRNAs), consisting of 1270 up-regulated and 1357 down-regulated lncRNAs, and 99 differentially expressed circular RNAs (DE-circRNAs), consisting of 68 up-regulated and 31 down-regulated circRNAs, were observed in the tx-J mice group when compared to the control mice group. Gene Ontology (GO) and pathway analyses revealed that DE-mRNAs were enriched in cellular processes, calcium signaling pathways, and mRNA surveillance pathways. In contrast, the DE-circRNAs-associated competing endogenous RNA (ceRNA) network was enriched for covalent chromatin modification, histone modification, and axon guidance, whereas the DE-lncRNAs-associated ceRNA network was enriched for dendritic spine, regulation of cell morphogenesis involved in differentiation, and mRNA surveillance pathway. The study presented the expression profiles of lncRNA, circRNA, and mRNA in the hippocampal tissue of tx-J mice. Furthermore, the study constructed PPI, ceRNA, and CNC expression networks. The findings are significant in comprehending the function of regulatory genes in WD associated with cognitive impairment. These results also offer valuable information for the diagnosis and treatment of WD. [ABSTRACT FROM AUTHOR]

The ATOX1 (Antioxidant Protein 1) is a human copper metal chaperone that plays an important role in cellular copper homeostasis. The protein is responsible for cytosolic copper absorption from CTR1 (copper transporter 1) and transport to the copper pumps in the Trans Golgi network to the ATP7A and ATP7B proteins. This review collects data on the antioxidant role of ATOX1, the gene role's in the angiogenesis regulation and cancer cell proliferation, and its role in the pathogenesis of copper-induced diseases—Wilson–Konovalov disease and Menkes disease. [ABSTRACT FROM AUTHOR]

Background: The liver has an important role in the different metabolic processes. So, inborn errors of metabolism will result in several metabolic disorders, which can cause acute or chronic liver disease leading to cirrhosis and liver cancer. Main body: In one of our Egyptian conferences, the United Conference of Hepatogastroenterology and Infectious Diseases (UCHID) 2022, our authors discussed the debates on the management of Wilson's disease, hereditary hemochromatosis, and alpha one anti-trypsin deficiency. Conclusion: The session summarized the pitfalls in the management of the 3 serious metabolic liver disorders with focused take-home messages to every physician. [ABSTRACT FROM AUTHOR]

Objective: To examine the clinical characteristics and influencing factors related to sleep disorders in patients with Wilson's disease (WD), and investigate its potential mechanisms. Methods: A total of 150 patients with WD (76 hepatic, 42 neurological, 32 asymptomatic form) and 150 age- and sex-matched control subjects were investigated using 3 standardized sleep questionnaires. Differences among 3 subtypes were discussed. Results: The mean Parkinson's disease sleep scale (PDSS) score of WD was lower than the controls (Z = − 4.426, P = 0.000), and their mean Epworth Sleepiness Scale (ESS) score as well as Pittsburgh sleep quality index (PSQI) score of WD was higher than that of the controls (t = 2.005, P = 0.048; t = 3.342, P = 0.001). The incidence of excessive daytime sleepiness (EDS) in WD group were significantly higher than the controls (X2 = 6.064, P = 0.014). Further analysis showed that total PDSS score of neurologic presentation group was lower than others (X2 = 6.131, P = 0.047), while the ESS score was higher (F = 3.817, P = 0.029). UWDRS showed a negative correlation with PDSS (r = − 0.440, P = 0.022) and has a higher negative correlation with PDSS in neurologic presentation group (r = − 0.732, P = 0.000). Conclusions: Patients with WD often suffer from sleep disturbances, mainly characterized by difficulty falling asleep, difficulty staying asleep, nocturnal motor symptoms (numbness, cramps, tremor), and daytime dozing. And the incidence of EDS is significantly higher than that of the controls. Sleep quality is worse in patients with WD of neurologic presentation than the other two groups. Furthermore, the worse of the symptoms, patients with WD suffer more serious of the sleep disorders especially in neurologic presentation group. [ABSTRACT FROM AUTHOR]

Background: Wilson disease (WD) is an inherited disorder of copper metabolism commonly involving the liver, cornea, and brain. Its incidence is increasing day by day worldwide. Early diagnosis and prompt treatment are the key for best outcome. Material and methods: A cross-sectional descriptive study was done from January 2014 to December 2019. Sixty children of both genders between 3 and 18 years were diagnosed by clinical and laboratory profile meeting selected criteria. Results: Mean age was 8.42 ± 2.6 years and male female ratio was 1.5:1. Consanguinity of marriage was found in 38.3% cases. Seventy percent of cases were hepatic, 16.7% were neuropsychiatric, 5.0% were hepatic with neuropsychiatric, and 8.3% cases were manifested asymptomatically. Asymptomatic and hepatic WD were reported between 3 and 10 years and most of the neuropsychiatric and hepatic with neuropsychiatric manifested after 10 years of age. More than 50% cases improved, a little more than 20% children died, 18.4% were unchanged and 6.6% were hepatic added neuropsychiatric manifestations. Most of the asymptomatic (100%) and hepatic (61.9%) cases improved. High mortality was found with 76.9% cases of acute liver failure (ALF), 7.7% case of chronic liver disease (CLD) and 25% cases of CLD with portal hypertension (CLD and PH). Most of the neuropsychiatric cases (90.0%), and approximately two-third (66.6%) of hepatic with neuropsychiatric cases remained unchanged. Neuropsychiatric manifestations were added in 15.4% cases of CLD and 25% cases of CLD with PH patient. The treatment was well tolerated in 66% children without any side effects. Low WBC (6.3%) and platelet count (4.3%), vomiting (6.3%), anorexia (4.3%), loss of taste (4.3%), rash (4.3%), and proteinuria (2.1%) were found in few cases. Conclusion: Majority of the children were presented with hepatic manifestations. More than half of patients with WD treated by D-penicillamine (DP) were improved. Significant mortality was found in acute liver failure whereas neuropsychiatric presentations had persistent abnormalities. No major side effects of DP was observed in most of the cases. Early diagnosis and prompt treatment were crucial for better outcome. [ABSTRACT FROM AUTHOR]

Background: Infection with coronavirus disease 2019 (COVID-19) can progress to the multisystem inflammatory syndrome in children (MIS-C). Patients with liver cirrhosis are at increased risk of complications. Case presentation: We report on a 13-year-old Wilson's disease patient who was referred for liver transplantation because of rapid deterioration in his hepatic condition. After admission, he developed fever, respiratory distress, coronary arteries dilatation on echocardiography, laboratory evidence of inflammation, and positive severe acute respiratory syndrome coronavirus (SARS-CoV-2) PCR. SARS-CoV-2-induced MIS-C was diagnosed. Inspite of aggressive management of MIS-C, progressive deterioration of the respiratory, liver, kidney, and cardiac functions occurred and he passed away. Conclusion: MIS-C is a serious possible complication leading to multiorgan failure and higher death rate especially in cirrhotic children. So, early diagnosis and management with higher level of care by a multidisciplinary team are warranted. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article discusses a case of a child with abdominal pain, arthralgia, palpable skin rash, hepatosplenomegaly, and pancytopenia. It mentions the etiology of the child's symptoms, which initially presented as Henoch-Schonlein purpura (HSP)/IgA vasculitis but was later diagnosed as Wilson disease. It also delves into the possible pathogenesis of IgA vasculitis and discusses the treatment approach for this condition in the context of Wilson disease.

Wilson's disease (WD) is a rare genetic disorder of copper metabolism that results in dysfunction of copper excretion into bile leading to its accumulation in the liver, brain, cornea, and kidney. Only a few epidemiological studies about WD have been carried out, with limited available data about the disease. The most common liver disease in Egypt is viral hepatitis, which masks other liver diseases, especially in adults. This review describes the establishment of the first specialized WD clinic in the Assiut Liver Center, Upper Egypt. This multidisciplinary clinic comprises stakeholders working in WD management from different specialties, including hepatologists, pediatric hepatologists, neuropsychiatrists, dieticians, radiologists, pathologists, and ophthalmologists. Over 2 years since the launch of the WD clinic in February 2020, a total of 64 WD suspected cases were referred to our center. The WD clinic at the Assiut Liver Center is a step to provide an integrated service for neglected diseases like WD. Besides the provided integrated services for WD patients, a family screening program is applied with satisfying results. [ABSTRACT FROM AUTHOR]

Introduction: Wilson's disease (WD) is a genetic disorder with pathological copper accumulation and associated clinical symptoms in various organs, particularly the liver and brain. Neurological disease is assessed with the clinical Unified Wilson's Disease Rating Scale (UWDRS). There is a lack of quantitative objective markers evaluating brain involvement. Recently, a semiquantitative brain magnetic resonance imaging (MRI) scale has been proposed, which combines acute toxicity and chronic damage measures into a total score. The relationship between MRI brain pathology and the MRI scale with disease form and neurological severity was studied in a large cohort. Methods: We retrospectively assessed 100 newly diagnosed treatment-naïve patients with WD with respect to brain MRI pathology and MRI scores (acute toxicity, chronic damage, and total) and analyzed the relationship with disease form and UWDRS part II (functional impairment) and part III (neurological deficits) scores. Results: Most patients had the neurological form of WD (55%) followed by hepatic (31%) and presymptomatic (14%). MRI examination revealed WD-typical abnormalities in 56% of patients, with higher pathology rates in neurological cases (83%) than in hepatic (29%) and presymptomatic (7%) cases. UWDRS part II and III scores correlated with the MRI acute toxicity score (r = 0.55 and 0.55, respectively), chronic damage score (r = 0.39 and 0.45), and total score (0.45 and 0.52) (all P < 0.01). Conclusions: Brain MRI changes may be present even in patients without neurological symptoms, although not frequently. The semiquantitative MRI scale correlated with the UWDRS and appears to be a complementary tool for severity of brain injury assessment in WD patients. [ABSTRACT FROM AUTHOR]

Background and Objective: There are limited data on the adverse events of d-penicillamine in Wilson's disease (WD) that can result in dose modification or treatment discontinuation. The objective of this study was to observe the adverse events related to d-penicillamine in patients with hepatic WD. Methods: A retrospective audit of prospectively registered hepatic WD patients at a tertiary care center between December 2006 and January 2020 was carried out. Demographic variables, laboratory parameters, and details of treatment were noted. Adverse events (AEs) related to d-penicillamine treatment, the timing and management of these AEs were analysed. Results: The study included 112 patients with hepatic WD on d-penicillamine. d-penicillamine intolerance was seen in 28/112 (25%) over 179 person-years. Of the 28 AEs, severe AEs leading to permanent d-penicillamine discontinuation occurred in 16 (57%) [never reintroduced 12 (43%), discontinued after intolerant to rechallenge, 4 (14%)], temporary cessation followed by reintroduction to initial dose 13 (46%) and continuation with reduced dose in 3 (11%) patients. Overall, most common AEs were hematological [16, 57% (pancytopenia n = 8, bicytopenia n = 5 and hemolytic anemia n = 3)] while renal adverse events (n = 7, 25%) constituted the most common indication for permanent discontinuation. Cytopenias developed beyond 12 months of d-penicillamine initiation whereas hemolytic anemia developed within first 3 months. Following d-penicillamine discontinuation in 25 patients, it was reintroduced to initial dose in 13/25 (52%), switched to trientine due to neurological worsening in 2/25 (8%) and switched to zinc in 10/25 (40%). In patients with reintroduction, gradual dose escalation was tolerated in 9/13 (69%) with a recurrence of AEs leading to permanent discontinuation in 4/13 (31%). Conclusion: D-penicillamine treatment is associated with significant AEs mainly related to blood, kidney, and skin. Temporary cessation of drug with reintroduction at a lower dose is an effective and safe option. [ABSTRACT FROM AUTHOR]

Degenerative changes in the basal ganglia (BG) are thought to contribute to neurological symptoms in Wilson's disease (WD). However, very little is known about whether and how the BG have an influence on prospective memory (PM) by interacting with the cerebral cortex. Here, we employed structural magnetic resonance imaging to systematically examine the effect of volume atrophy of BG on cortical thickness and to evaluate the relationships between cortical thickness of regions associated with BG atrophy and PM performance in WD. Cortical thickness atrophy in the left temporal pole and medial frontal gyrus are not related to degenerative changes in BG. Cortical thickness in the left superior frontal gyrus and right orbitofrontal gyrus (ORB) have stronger correlations with volume atrophy of the left accumbens, pallidum, and putamen in WD when compared with healthy controls. Furthermore, the cortical thickness of the right ORB is not only significantly correlated with PM performance but can also distinguish the severity of PM impairment in WD. Additionally, the middle cingulate cortex was related to volume atrophy of the accumbens, and its cortical thickness has a significant positive correlation with event-based PM. Together, these findings highlight that BG-orbitofrontal circuits may serve as neural biomarkers of PM and provide implications for the neural mechanisms underlying cognitive impairment in WD. [ABSTRACT FROM AUTHOR]

Typically, diagnosis is based on the association of compatible clinical signs and classical biological triad: low ceruloplasmin (Cp), low serum copper and elevated 24-h urinary copper excretion. We conclude from this clinical case that a standard but incomplete serum copper test with no abnormality cannot refute Wilson's disease hypothesis when the clinical suspicion is strong. Kayser-Fleischer ring is present in almost all Wilson's disease patients at disease diagnosis when neurologic symptoms are observed [[2]]. [Extracted from the article]

Exchangeable copper (CuEXC), mainly comprised copper (Cu) bound to albumin, has been proposed as a specific marker of Cu overload in Wilson's disease (WD). To the author's knowledge, there are no methods capable of determining reliably CuEXC to meet the requirements and challenges faced by a clinical trial. The present work describes a novel speciation strategy for the determination of the main Cu-species in human serum by anion-exchange high-performance liquid chromatography coupled to inductively coupled plasma mass spectrometry (HPLC-ICP-MS). A label-free protein quantification approach was conducted where the concentration of Cu associated to the protein fraction was based on its relative peak area distribution and the total Cu concentration in the sample. Such a methodology was characterized in terms of selectivity, sensitivity, precision, and robustness. Due to the lack of speciated Cu-reference materials, protein recovery was assessed by comparison with that of species-specific (SS) isotope dilution (ID). For this, a double SS HPLC-ICP-IDMS method for Cu-albumin was developed and presented here for the first time. Three human sera (two frozen LGC8211 and ERM®-DA250a, and the lyophilised Seronorm™ Human) were analyzed using both the relative and ID quantification methods. The validated relative approach, with relative expanded uncertainties (k = 2) between 5.7 and 10.1% for Cu-albumin concentrations ranging from 112 to 455 μg kg−1 Cu, was found to be able to discriminate between healthy and WD populations in terms of Cu-albumin content. Also, using such methodology, underestimation of CuEXC by the classical EDTA/ultrafiltration method was demonstrated. The methodology developed in this work will be invaluable for quality control assessment and WD drug monitoring. [ABSTRACT FROM AUTHOR]

Abnormal blink reflex (BR) results mainly from the dysfunction of reticular brainstem pathways and is one of the features of degenerative brain disorders. We aimed to investigate whether patients with Wilson's disease (WD) have abnormal BR. This was a prospective, observational, single-center study. BR was assessed in accordance with generally accepted standards in 44 newly diagnosed treatment-naïve and 66 treated patients with WD. Any abnormal parameters in BR were observed in 45.5% treatment-naïve patients and 37.9% treated patients (p = 0.429). We also did not observe significant differences in BR parameters and frequency of abnormal findings between treated and treatment naïve patients. Abnormal findings in any of the BR parameters were more frequent in patients with neurological vs. non-neurological presentation (57.5 vs. 28.6%, p = 0.002), present vs. absent Kayser–Fleischer ring (73 vs. 21.5%, p < 0.001), and typical vs. no typical WD abnormalities in brain MRI (50% vs. 24.4%, p = 0.009). In addition, longer median R1 and R2 latencies, both ipsilateral and contralateral, were significantly more frequent in neurological than non-neurological WD patients, those with Kayser–Fleischer rings, and those with abnormal MRI findings typical of WD. Our results confirm frequent BR abnormalities in WD, which may be explained by the pathological influence of copper deposits in the circuit linking the basal ganglia, cerebellum and brainstem. [ABSTRACT FROM AUTHOR]

The article presents answers to a clinical quiz about nephrotic range proteinuria in an adolescent with Wilson's disease.

Although lupus induced by penicillamine, the first-line medication for Wilson's disease, is well-documented, primary systematic lupus erythematosus (SLE) co-occurring with Wilson's disease has only rarely been reported. Symptom overlap can add to difficulties in making the correct and complete diagnosis of these two systemic diseases. An 18-year-old female was diagnosed with simultaneous Wilson's disease and SLE and was successfully treated with hydroxychloroquine and oral zinc. We also reviewed the literature for cases of Wilson's disease co-occurring with SLE not induced by penicillamine and found six other cases. Clinical presentations, diagnoses, treatments, and outcomes were analyzed and summarized to expand our understanding of this rare condition. The most frequent diagnostic clues to Wilson's disease in patients with SLE included unexplained liver damage despite well-controlled SLE, extrapyramidal symptoms and signs, hyper-intense signals of the basal ganglia bilaterally on T2-weighted and fluid-attenuated inversion recovery (FLAIR) MRI images, and Kayser-Fleischer (K-F) rings on physical examination. Penicillamine should be avoided or used cautiously in Wilson's disease patients complicated by SLE. The overall prognosis is good if treated in a timely manner. Key Points • SLE complicated by Wilson's disease or the co-occurrence of the two conditions in the absence of penicillamine may exist in rare conditions. • The diagnostic clues for identifying Wilson's disease in SLE patients may include unexplained liver damage despite well-controlled SLE, extrapyramidal symptoms and signs, and K-F rings found by physical examination. • Penicillamine should be avoided or used cautiously in Wilson's patients with SLE. [ABSTRACT FROM AUTHOR]