Wilson's Disease Research Articles

Pregnancies in Women After Liver Transplant due to Wilson's Disease—Case Series

Wilson's disease is a rare autosomal recessive disorder. Due to a defect in membrane copper transporter, copper is not excreted in the bile and accumulates in the tissues. The only treatment for acute liver failure in Wilson's disease is a liver transplant. AimAssessment of the course of pregnancies and comparison of obstetric outcomes in female liver transplant recipients in the course of Wilson's disease. MethodologyRetrospective analysis of data of women, who were pregnant and gave birth in the years: 2017 to 2023. Evaluation of their liver function used pharmacotherapy and obstetric outcomes. ResultsWe recorded 11 pregnancies in liver transplantation recipients due to Wilson's disease. Ten single pregnancies and 1 twin (DCDA) were observed. In all pregnancies, graft functions and immunosuppressive drug concentrations were monitored. Three women suffered from epilepsy, one was diagnosed with psychiatric disorder. Two were diagnosed with cholestasis, and another 2 with gestational diabetes. Two of them were treated for pregnancy-induced hypertension and 2 developed preeclampsia. Deterioration of liver function parameters in pregnancy was observed in 2 cases. In total, 8 full-term babies were born and 4 late-preterm, including twins at 35 weeks of gestation. Seven pregnancies were delivered by caesarean section and 4 delivered vaginally. No complications in early postpartum period have been reported. ConclusionsWomen with Wilson's disease treated with organ transplantation have a chance of successful pregnancies and deliveries.

Wilson disease: the diagnostic challenge and treatment outcomes in a series of 262 cases.

Wilson disease (WD) is an autosomal recessive disorder that leads to organ toxicity due to copper overload. Early diagnosis is complicated by the rarity and diversity of manifestations. To describe the diagnostic features and response to treatment in our cohort of WD patients. This was a retrospective analysis of 262 WD patients stratified by clinical presentation, complementary exams, ATP7B genotyping, and response to treatment. Symptoms occurred at an average age of 17.4 (7-49) years, and patients were followed up for an average of 9.6 (0-45) years. Patients presented mainly with hepatic (36.3%), neurologic (34.7%), and neuropsychiatric (8.3%) forms. Other presentations were hematologic, renal, or musculoskeletal, and 16.8% of the patients were asymptomatic. Kayser-Fleischer rings occurred in 78.3% of the patients, hypoceruloplasminemia in 98.3%, and elevated cupruria/24h in 73.0%, with an increase after D-penicillamine in 54.0%. Mutations of the ATP7B gene were detected in 84.4% of alleles. Brain magnetic resonance imaging showed abnormalities in the basal ganglia in 77.7% of patients. D-penicillamine was the first choice in 93.6% of the 245 patients, and 21.1% of these patients were switched due to adverse effects. The second-line therapies were zinc and trientine. The therapeutic response did not differ significantly between the drugs (p = 0.2). Nine patients underwent liver transplantation and 82 died. Wilson disease is diagnosed at a late stage, and therapeutic options are limited. In people under 40 years of age with compatible manifestations, WD could be considered earlier in the differential diagnosis. There is a need to include ATP7B genotyping and therapeutic alternatives in clinical practice.

Elevated salivary copper levels in patients with Wilson's disease

Elevated salivary copper levels in patients with Wilson's disease

Pregnancy in Liver and Kidney Female Recipient: A Case Report

Deterioration of kidney function after orthotopic liver transplantation is a common complication. It may occur due to perioperative acute kidney injury (AKI) and pre-existing or developing chronic kidney disease (CKD). AKI is described in early postoperative period in more than half of the recipients whereas the main cause of CKD is pharmacotherapy. When end-stage renal failure occurs, patients may be qualified for additional transplantations.A case report: We present a rare case of 27-year-old female who as teenager underwent two liver transplantations due to Wilson's disease. Operations were complicated by systemic infection and multiple organ failure. The kidneys did not regain their function, therefore, after 6 months of dialysis, the organ was transplanted. In total, three organ transplantations were performed. Due to the patient's willingness and good graft functions, patient started trying to conceive. Three months before successful conception, immunosuppressive therapy was changed to tacrolimus and azathioprine. Pregnancy was complicated by pregnancy induced hypertension and its course was closely monitored. Organs' functions and immunosuppressive therapy were regularly assessed. Due to the pre-eclampsia developed in the 35th week of gestation, a caesarean section was performed and she gave birth to daughter weighing 2350g (Apgar 7-7-8). Women decided on breastfeeding. No obstetric complications or graft function deterioration were observed in the early postpartum period. Mother and daughter left home after 7 days of hospitalization.Conclusions: The presented clinical situation proves that successful pregnancy is possible by multi-organ transplantation recipients, without impairing the graft functions. Therefore, it requires adequate preparation and increased care.

Plasma exchange improves survival in acute liver failure- An updated systematic review and meta-analysis focussed on comparing within single etiology.

Therapeutic plasma exchange (PLEX) is increasingly used in patients with acute liver failure (ALF) as either stand-alone therapy or bridge to liver transplantation. Etiology plays a major role in prognosis of these patients and benefit of PLEX may consequently differ across etiologies. This systematic review and meta-analysis aims to evaluate the efficacy of PLEX in treating ALF, focussing on studies with single etiology. We conducted a systematic literature search and identified studies comparing PLEX vs. standard medical therapy (SMT) for patients with ALF across all age groups. The protocol was registered in theInternational Prospective Register of Systematic Reviews (PROSPERO) (CRD42023442383). Pooled risk-ratios were determined by Mantel-Haenszel method within a random effect model. Primary outcome was mortality at ≤ 60-days and 90days. Secondary outcome was adverse events attributable to PLEX. Eight studies (pooled sample size in PLEX arm:284; randomized trials:2; Comparative cohorts:6) with retrievable data on ALF were included in this systematic review. Analysis showed that PLEX was associated with significant reduction in mortality at ≤ 60-days (RR 0.64; CI, 0.51-0.80; P < 0.001) and at 90-days (RR 0.67; CI, 0.50-0.90; P = 0.008) as compared to SMT. On sub-group analysis, the survival benefit was noted irrespective of the volume of plasma exchanged during PLEX. Three studies (pooled sample size in PLEX arm: 110; all comparative cohorts) were identified, which included patients with a single etiology for ALF. These studies included patients with Wilson's disease, rodenticidal hepatotoxicity and acute fatty liver of pregnancy. Pooled analysis of studies with single etiology ALF showed better reduction in ≤ 90-day mortality with PLEX (RR 0.53; CI, 0.37-0.74; P < 0.001). Studies reported no major side-effects attributable to PLEX. PLEX is safe and improves survival, independent of the volumes utilized, in patients with ALF as compared to standard medical treatment. The survival benefit is especially pronounced in studies restricted to single etiology.

Clinical profile of children with metabolic liver diseases presenting in a tertiary care hospital of Eastern India

Clinical profile of children with metabolic liver diseases presenting in a tertiary care hospital of Eastern India

Neuropsychiatric Manifestations and Neuroimaging Changes of Neurologic Wilson Disease–A Cross Sectional Study

Background: Wilson disease is genetic disorder of copper metabolism which causes hepatic &amp; neurologic manifestation mainly. Chelator therapy is usually given as first line treatment in symptomatic wilson disease. Objective: Objective of our study was to evaluate the neuropsychiatric menufestations of wilson disease. Methods: A Cross sectional study was conducted at Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, a tertiary care premier Postgraduate Medical Institution of Bangladesh. Forty five (45) patients of neurologic wilson disease were evaluated at In-patient department of Paediatric Neurology, during the period of January 2015 to December 2020. Diagnosis of Neurologic wilson disease was done, based on the characteristic clinical features of progressive deterioration of scholastic performances, dysarthria and gait disorder along with ophthalmologic findings, biochemical &amp; neuroimaging findings. Results: Total numbers of studied cases were 45. Mean age was 124.65± 20.69 months and male to female ratio was 1.8:1. Most of the patient (83.33%) arrived from poor socio-economic background and rural area (66.67%) of Bangladesh. Among them 20.0% had history of consanguineous mating parents and 17.78% had another affected sibs. Common presenting features were progressive deterioration of school performance (89.74%), gait disturbance (92.31%), dysarthria (92.31%) and dystonia (41.03%) of our studied children. Neuropsychiatric manifestations were very common among the affected children. Changes in behavior was present in 62.22% cases, and among them mania were present in 57.77% children. Other common neuropsychiatric manifestations were depression (35.55%), generalized anxiety disorder in 31.11% and loss of memory in 20% cases. Ophthalmological manifestations like KF ring (83.33%) also found in majority of patient. Neuroimaging study showed basal ganglia hyperintensity in 63.63.% , white matter hyper intense signal changes 18.18% cases and ischemic change in grey matter in 18.18% cases. Conclusion: In our study about two third cases of Neurologic Wilson diseases may present with Neuropsychiatric manifestations in children. Behavior changes were commonest neuropsychiatric manifestations which includes depression, mania, generalized anxiety disorder and loss of memory.In neuroimaging study bilateral basal ganglia hyperintensity were found in about three-fourth cases of our studied children. J Bangladesh Coll Phys Surg 2024; 42: 144-148

Changing etiological spectrum of acute liver failure.

Acute liver failure (ALF) is an uncommon but potentially dramatic syndrome characterized by massive hepatic necrosis and has a very high mortality rate of 50% to75% without liver transplantation. This study is aimed at analyzing the etiological spectrum of ALF patients and compare these with ALF mimicssuch as malaria, dengue fever and other tropical infectious diseases. The study population included patients who presented with ALF and ALF mimics in a tertiary care center over two years. We retrospectively analyzed the patient case files and a comparison was made concerning the baseline demographic details, clinical profile, laboratory values and outcomes. Sixty-three patients were assessed, with 32 in ALF and 31 in ALF mimics group. The most common cause for ALF was hepatitis A virus (25%), followed by hepatitis B virus (18.7%), drug-induced liver injury (12.7%), autoimmune hepatitis (12.5%), hepatitis E virus (9.3%) and Wilson's disease (6.25%). In the ALF mimics group, malaria (58.06%) was the most common cause, followed by dengue fever (16.1%), leptospirosis (12.9%) and scrub typhus (12.9%). Patients in the ALF mimics group had significantly higher incidence of fever (p = 0.001), hepatosplenomegaly (p = 0.01), anemia (p = 0.02) and shorter jaundice to encephalopathy duration (p = 0.032) as compared to the ALF group, while higher transaminase levels (p = 0.03), bilirubin (p = 0.01), prothrombin time (p = 0.01), serum ammonia (p = 0.02) and mortality (p = 0.02) were observed in ALF patients. The most common cause for ALF was hepatitis A virus, followed by hepatitis B virus, while in ALF mimics it was malaria followed by dengue fever, in our study. Patients of ALF mimics can have similar presentation, but a high index of suspicion and awareness is required to identify the common infectious ALF mimics for early diagnosis.

Wilson Disease: Copper-Mediated Cuproptosis, Iron-Related Ferroptosis, and Clinical Highlights, with Comprehensive and Critical Analysis Update.

Wilson disease is a genetic disorder of the liver characterized by excess accumulation of copper, which is found ubiquitously on earth and normally enters the human body in small amounts via the food chain. Many interesting disease details were published on the mechanistic steps, such as the generation of reactive oxygen species (ROS) and cuproptosis causing a copper dependent cell death. In the liver of patients with Wilson disease, also, increased iron deposits were found that may lead to iron-related ferroptosis responsible for phospholipid peroxidation within membranes of subcellular organelles. All topics are covered in this review article, in addition to the diagnostic and therapeutic issues of Wilson disease. Excess Cu2+ primarily leads to the generation of reactive oxygen species (ROS), as evidenced by early experimental studies exemplified with the detection of hydroxyl radical formation using the electron spin resonance (ESR) spin-trapping method. The generation of ROS products follows the principles of the Haber-Weiss reaction and the subsequent Fenton reaction leading to copper-related cuproptosis, and is thereby closely connected with ROS. Copper accumulation in the liver is due to impaired biliary excretion of copper caused by the inheritable malfunctioning or missing ATP7B protein. As a result, disturbed cellular homeostasis of copper prevails within the liver. Released from the liver cells due to limited storage capacity, the toxic copper enters the circulation and arrives at other organs, causing local accumulation and cell injury. This explains why copper injures not only the liver, but also the brain, kidneys, eyes, heart, muscles, and bones, explaining the multifaceted clinical features of Wilson disease. Among these are depression, psychosis, dysarthria, ataxia, writing problems, dysphagia, renal tubular dysfunction, Kayser-Fleischer corneal rings, cardiomyopathy, cardiac arrhythmias, rhabdomyolysis, osteoporosis, osteomalacia, arthritis, and arthralgia. In addition, Coombs-negative hemolytic anemia is a key feature of Wilson disease with undetectable serum haptoglobin. The modified Leipzig Scoring System helps diagnose Wilson disease. Patients with Wilson disease are well-treated first-line with copper chelators like D-penicillamine that facilitate the removal of circulating copper bound to albumin and increase in urinary copper excretion. Early chelation therapy improves prognosis. Liver transplantation is an option viewed as ultima ratio in end-stage liver disease with untreatable complications or acute liver failure. Liver transplantation finally may thus be a life-saving approach and curative treatment of the disease by replacing the hepatic gene mutation. In conclusion, Wilson disease is a multifaceted genetic disease representing a molecular and clinical challenge.

The cost implications of Wilson disease among hospitalized patients: analysis of USA hospitals.

In this study, we used a national cohort of patients with Wilson's disease (WD) to investigate the admissions, mortality rates, and costs over the captured period to assess specific subpopulations at higher burden. Patients with WD were selected using 2016-2019 National Inpatient Sample (NIS). The weighted estimates and patient data were stratified using demographics and medical characteristics. Regression curves were graphed to derive goodness-of-fit for each trend from which R2 and P values were calculated. Annual total admissions per 100 000 hospitalizations due to WD were 1075, 1180, 1140, and 1330 ( R2 = 0.75; P = 0.13) from 2016 to 2019. Within the demographics, there was an increase in admissions among patients greater than 65 years of age ( R2 = 0.90; P = 0.05) and White patients ( R2 = 0.97; P = 0.02). Assessing WD-related mortality rates, there was an increase in the mortality rate among those in the first quartile of income ( R2 = 1.00; P < 0.001). The total cost for WD-related hospitalizations was $20.90, $27.23, $24.20, and $27.25 million US dollars for the years 2016, 2017, 2018, and 2019, respectively ( R2 = 0.47; P = 0.32). There was an increasing total cost trend for Asian or Pacific Islander patients ( R2 = 0.90; P = 0.05). Interestingly, patients with cirrhosis demonstrated a decreased trend in the total costs ( R2 = 0.97; P = 0.02). Our study demonstrated that certain ethnicity groups, income classes and comorbidities had increased admissions or costs among patients admitted with WD.

Exploration of TCM syndrome types of the material basis and risk prediction of Wilson disease liver fibrosis based on 1H NMR metabolomics

Wilson disease (WD) is an autosomal recessive disorder characterized by abnormal copper metabolism. The accumulation of copper in the liver can progress to liver fibrosis and, ultimately, cirrhosis, which is a primary cause of death in WD patients. Metabonomic technology offers an effective approach to investigate the traditional Chinese medicine (TCM) syndrome types of WD-related liver fibrosis by monitoring the alterations in small molecule metabolites within the body. In this study, we employed 1H-Nuclear Magnetic Resonance (1H NMR) metabonomics to assess the metabolic profiles associated with five TCM syndrome types of WD-related liver fibrosis and analyzed the diagnostic and predictive capabilities of various metabolites. The study found a variety of metabolites, each with varying levels of diagnostic and predictive capabilities. Furthermore, the discerned differential metabolic pathways were primarily associated with various pathways involving carbohydrate metabolism, amino acid metabolism, and lipid metabolism. This study has identified various characteristic metabolic markers and pathways associated with different TCM syndromes of liver fibrosis in WD, providing a substantial foundation for investigating the mechanisms underlying these TCM syndromes.

Analysis of Disease Adaptation Ability in Patients with Hepatolenticular Degeneration: Current Status and Influencing Factors

Objective To investigate This study aims to examine the disease adaptation ability capabilities of hepatolenticular degeneration patients during their treatment treatment, and explore to identify the factors influencing these affecting their adaptation ability. abilities. Methods A total of 210 hepatolenticular degeneration patients in treatment were selected by convenience sampling method, method and was employed to select 210 patients undergoing treatment for hepatolenticular degeneration. The investigation utilized a general information questionnaire, the Disease Acceptance Scale AIS-CHI questionnaire, and the Chinese version of the Simple Roy Coping with Adaptation Scale Scale. were used for investigation. Results The results of multiple Multiple linear regression analysis showed revealed that factors such as place of residence, education level, occupation, medical payment mode, and average monthly income of family members significantly influenced were the main factors affecting the disease adaptation ability capabilities of these patients. In conclusion, patients withpatients. In conclusion, patients with hepatolenticular degeneration exhibit suboptimal patients. Conclusion Hepatolenticular degeneration patients show poor adaptation ability abilities during treatment. Therefore, Consequently, it is incumbent upon the responsibility of medical staff to guide assist patients and their families to in actively managing cope with the their disease status status, thereby facilitating so as to better adapt to the disease adaptation and ensuring thus ensure the physiological and psychological health well-being of patients post-discharge.

An ESIPT active coumarin-diphenyl azine-based AIEgen: Nanomolar Cu2+ ion sensing, Latent Fingerprinting, live-cell imaging, and real sample analysis

Designing economical and sensitive chemosensors for detecting important metal ions, like Cu2+ ions, is essential and remains a hot topic worldwide. In this investigation, we extended our investigation to design a specific diphenyl-azine-based skeletal system for the selective and sensitive detection of Cu2+ions. We reported a coumarin-diphenyl-azine-based AIEgen (C-1) using an improvised methodology with a large Stoke's shift (∼245 nm) for precisely sensing copper ions in solid, solution, and biological cells. The AIE-ESIPT properties of C-1 were validated using various sophisticated techniques. C-1 was found to be a promising selective and sensitive sensor of Cu2+ ions (nanomolar LOD value ∼10.38 nM) via colorimetric and TURNOFF fluorometric ways. The practical applicability of C-1 was analyzed via real-time estimation of copper ions in water samples (obtained from three varied locations) and in biological samples (urine and serum). The satisfactory recovery with a low RSD value indicates the potential of C-1 in detecting copper ions in actual samples. Estimating copper ions in urine and blood samples demonstrates the usefulness of C-1 in diagnosing disorders like Wilson's disease, which is caused by high concentrations of copper ions in the body. Additionally, we have detected Cu2+ions in live cells (HeLa cells) and carried out Latent Fingerprinting (Level 1 and Level 2) to validate its versatility in physiological and forensic applications. Overall, the proposed C-1 AIEgen is an ultrasensitive Cu2+ions sensor with innumerable applications in the physical world.

Evaluation of ventricular arrhythmia in children with Wilson's disease; cardiac electrophysiological balance index (iCEB)

Evaluation of ventricular arrhythmia in children with Wilson's disease; cardiac electrophysiological balance index (iCEB)

Assessment and factors affecting quality of life among patients with Wilson’s disease

Wilson’s disease is caused by abnormal copper metabolism resulting in deposition in various organs, including the brain, liver, and cornea, thus disrupting organ function. It is characterized by encephalopathy, extrapyramidal symptoms, progressive liver failure, and copper ring deposition in the cornea. Management of this disease should include quality of life maintenance; however, relevant studies on this topic are lacking. This study aimed to assess the factors affecting the quality of life (QoL) of patients with Wilson’s disease. A cross-sectional survey using convenience sampling was conducted between July 2020 and March 2021 at the hospital. Data on patient characteristics, 36-item Short-Form General Health Survey, Uniform Wilson Disease Rating Scale, and Hamilton Depression Rating Scale scores were collected. Associations among quality of life depression, anxiety, and Wilson’s disease progression were examined using Pearson correlation analysis. Factors affecting the quality of life of patients, including depression, anxiety, liver function, clinical symptoms, diet, liver function, brain magnetic resonance imaging (MRI) findings, disease duration, Barthel Index, and Morse scores were examined using multivariate linear regression analysis. This study included 134 patients with Wilson’s disease whose mean age was 29.12 ± 8.59 years. The mean QoL score in the patient group was 71.38 ± 9.55 points and was negatively correlated with anxiety (r = − 0.883, P = 0.000), depression (r = − 0.852 P = 0.000), and clinical symptoms (r = − 0.542, P = 0.000) scores. Anxiety, depression, and clinical symptoms severity are vital factors for the QoL of patients with Wilson’s disease. The study provides foundational evidence to design novel interventions, including symptom management, diet, and self-care ability, which can help in improving the quality of life in patients with Wilson’s disease and decreasing the burden associated with this disease.

Burden of Wilson Disease among patients and care partners in the United States: results from a cross-sectional survey

Objective This study assessed the burden of Wilson Disease (WD) among patients and care partners (WD-CPs) in the US and compared it to a US general population of adults (GPs) and care partners (GP-CPs). Methods This cross-sectional, self-reported survey included patients with WD and WD-CPs aged ≥18 years recruited through the Wilson Disease Association (WDA), while data for GPs and GP-CPs were obtained from the 2022 National Health and Wellness Survey. GPs and GP-CPs were propensity score matched (3:1) with WD patients and WD-CPs for demographics and health characteristics. Bivariate analysis evaluated differences in comorbidity burden and health-related outcomes of the WD cohorts compared to matched GP cohorts. Results Thirty-seven patients with WD and 53 WD-CPs completed the survey. Most patients reported some treatment burden (73.3%), experienced sleep problems (60%), and visited a healthcare provider (HCP) in the past 6 months (91.9%). Compared with matched GPs, patients with WD had a significantly higher mortality risk (p < .001) and reported greater rates of chronic liver disease, cirrhosis (both, p < .001), migraines (p = .032), non-alcoholic steatohepatitis (p = .004), sleep problems (p = .009) and HCP visits (p = .002). Most WD-CPs (75.5%) reported high burden of caring (mean ZBI-12 score, 26.5) and more negative impact on esteem than GP-CPs. Conclusion This study highlights the burden of WD experienced by patients and WD-CPs, with patients experiencing high treatment burden, comorbidity burden and healthcare resource utilization, and WD-CPs experiencing high impact of caring, including impact on employment and self-esteem.

Effect of high-frequency repetitive transcranial magnetic stimulation on cognitive impairment in WD patients based on inverse probability weighting of propensity scores.

Hepatolenticular degeneration [Wilson disease (WD)] is an autosomal recessive metabolic disease characterized by copper metabolism disorder. Cognitive impairment is a key neuropsychiatric symptom of WD. At present, there is no effective treatment for WD-related cognitive impairment. In this study, high-frequency repetitive transcranial magnetic stimulation (rTMS) was used to treat WD-related cognitive impairment, and inverse probability weighting of propensity scores was used to correct for confounding factors. The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Auditory Verbal Learning Test (AVLT), Boston Naming Test (BNT), Clock Drawing Test (CDT) and Trail Making Test (TMT) were used to evaluate overall cognition and specific cognitive domains. The MMSE, MoCA and CDT scores after treatment were significantly different from those before treatment (MMSE: before adjustment: OR = 1.404, 95% CI: 1.271-1.537; after adjustment: OR = 1.381, 95% CI: 1.265-1.497, p < 0.001; MoCA: before adjustment: OR = 1.306, 95% CI: 1.122-1.490; after adjustment: OR = 1.286, 95% CI: 1.104; AVLT: OR = 1.161, 95% CI: 1.074-1.248; after adjustment: OR = 1.145, 95% CI: 1.068-1.222, p < 0.05; CDT: OR = 1.524, 95% CI: 1.303-1.745; after adjustment: OR = 1.518, 95% CI: 1.294-1.742, p < 0.001). The BNT and TMT scores after adjustment were not significantly different from those before adjustment (BNT: before adjustment: OR = 1.048, 95% CI: 0.877-1.219; after adjustment: OR = 1.026, 95% CI: 0.863-1.189, p > 0.05; TMT: before adjustment: OR = 0.816, 95% CI: 1.122-1.490; after adjustment: OR = 0.791, 95% CI: 0.406-1.176, p > 0.05). High-frequency rTMS can effectively improve cognitive impairment, especially memory and visuospatial ability, in WD patients. The incidence of side effects is low, and the safety is good.

Synthesis and Biological Activities of Some Metal Complexes of Peptides: A Review.

Peptides, both natural and synthetic, are well suited for a wide range of purposes and offer versatile applications in different fields such as biocatalysts, injectable hydrogels, tumor treatment, and drug delivery. The research of the better part of the cited papers was conducted using various database platforms such as MetalPDB. The rising prominence of therapeutic peptides encompasses anticancer, antiviral, antimicrobial, and anti-neurodegenerative properties. The metals Na, K, Mg, Ca, Fe, Mn, Co, Cu, Zn, and Mo are ten of the twenty elements that are considered essential for life. Crucial for understanding the biological role of metals is the exploration of metal-bound proteins and peptides. Aside from essential metals, there are other non-essential metals that also interact biologically, exhibiting either therapeutic or toxic effects. Irregularities in metal binding contribute to diseases like Alzheimer's, neurodegenerative disorders, Wilson's, and Menkes disease. Certain metal complexes have potential applications as radiopharmaceuticals. The examination of these complexes was achieved by preforming UV-Vis, IR, EPR, NMR spectroscopy, and X-ray analysis. This summary, although unable to cover all of the studies in the field, offers a review of the ongoing experimentation and is a basis for new ideas, as well as strategies to explore and gain knowledge from the extensive realm of peptide-chelated metals and biotechnologies.

Phenotype and molecular characterization of Wilson's disease in Morocco

Background and study aimsIn Morocco the prevalence of Wilson disease (WD) and the spectrum of mutations are not known. The aim of the present study was to estimate the prevalence of WD in Morocco, to evaluate the phenotype among a large cohort of WD patients, and to characterize ATP7B variants in a subgroup of WD patients. Patients and methodsWe collected data from 226 patients admitted to five university hospital centers in Morocco between 2008 and 2020. The diagnosis was based on clinical manifestations, function tests and biochemical parameters. The genotype was characterized in 18 families diagnosed at the University Hospital Center of Marrakesh, by next generation sequencing. ResultsThe mean annual prevalence in Morocco was 3.88 per 100,000 and the allele frequency was 0.15 %. Among the 226 patients included (121 males and 105 females), 196 were referred for a hepatic or neurological involvement and 30 were asymptomatic. The mean age at diagnosis was 13 ± 5.1 years (range: 5 - 42 years). Consanguinity was found in 63.3 % of patients. The mean duration of illness was 2.8 ± 1.9 years. Kayser-Fleischer rings were found in 131 (67.9 %) of 193 patients. Among the 196 symptomatic patients, 141/159 (88.7 %) had low serum ceruloplasmin (<0.2 g/L) and a high 24-hours urinary copper (>100 μg/day) was found in 173/182 (95.1 %) patients. The initial treatment was D-penicillamine in 207 patients, zinc acetate in five, zinc sulfate in five, and nine patients were not treated; 60/207 (29 %) patients have stopped treatment. A total of 72 patients died; the mortality rate was 31.9 %. Eight different ATP7B variants were identified among the 18 patients studied, of which two were novel (p.Cys1104Arg and p.Gln1277Hisfs*52), and six previously published (p.Gln289Ter, p.Cys305Ter, p.Thr1232Pro, p.Lys1020Arg, p.Glu583ArgfsTer25 and c.51+4A>T). All informative patients were homozygous for the disease-causing mutation. ConclusionIn Morocco, a high prevalence due to consanguinity and a high mortality rate due to the difficulty of diagnosis and lack of treatment were observed in WD patients. NGS sequencing identified new ATP7B variants in WD patients from Morocco.

Exploring the Content Validity of the Unified Wilson Disease Rating Scale: Insights from Qualitative Research.

Wilson disease (WD) is a rare metabolic disorder of impaired copper transport manifesting in hepatic, neurological, and psychiatric symptoms. To evaluate the clinical symptoms of WD in clinical trials, a group of clinicians created the Unified Wilson Disease Rating Scale (UWDRS). Content validity of this scale has not been established. The aim of this study was to evaluate the content validity of the UWDRS PartII from the patient perspective. This study utilized multiple qualitative research methods including concept elicitation interviews, concept/instrument mapping, and cognitive debriefing interviews. Concept elicitation interviews with a sample of patients with WD and one or more neurological signs/symptoms identified several signs, symptoms, and impacts related to neurological dysfunction, strengthening our understanding of the importance of the neurological aspects of the WD patient experience. Mapping neurological concepts to PartII and III items of the UWDRS showed complete coverage of all salient neurological concepts and near complete coverage of all neurological concepts reported by patients in concept elicitation interviews. Item debriefing of PartII of the UWDRS revealed that patients generally found the items clear and personally relevant to their experience with WD. Overall, the findings from this study provide evidence for the content validity of the UWDRS PartII and supportive evidence for the content validity of PartIII. The UWDRS should be used in conjunction with additional clinical outcomes assessments, specifically those evaluating the hepatic and psychiatric signs/symptoms of WD, to provide a comprehensive evaluation of the WD patient experience.