Wilson Disease: Update on Pathophysiology and Treatment Wilson Disease Webinar: Genetic Testing and Emerging Treatments. After interviews with clinicians, the model was expanded to include 45 signs/symptoms and 14 impacts. Changes in mood. These findings may ultimately support the development of meaningful and relevant treatments for WD that address the signs, symptoms and impacts that matter most to patients. 2012;4(1):510. The patient-reported experience of living with Wilson disease. The following impacts are not depicted due to not having been probed for bothersome ratings: Inability to walk/wheelchair bound, and Alcohol/abuse. Provided by the Springer Nature SharedIt content-sharing initiative. Symptoms are typically related to the brain and liver.Liver-related symptoms include vomiting, weakness, fluid build-up in the abdomen, swelling of the legs, yellowish skin, and itchiness.Brain-related symptoms include tremors, muscle stiffness, trouble in speaking, personality changes, anxiety, and psychosis. The literature review returned 30 articles, from which 45 concepts (35 signs/symptoms and 10 impacts) were selected for inclusion in the preliminary conceptual model. Supplemental material to support the methods and results. Your privacy choices/Manage cookies we use in the preference centre. One of the livers jobs is to maintain the balance of copper in the body. It was developed by the Canadian Liver Foundation as a means to link Canadians like you who have a family member who has liver disease, who care for someone who suffers from liver disease, or who have been diagnosed with a liver disease, to talk about your concerns with a peer in a similar situation. Several hepatic (6), neurological (6), and psychiatric (11) signs and symptoms were considered salient (defined as5 people ever experiencing a concept and the average peak bother rating5). All authors contributed to the development of this manuscript. Additionally, it defines subgroups of patients (those with hepatic as well as neurological and psychiatric signs/symptoms, and those without neurological signs/symptoms) that may be key for generating productive dialogue with each group of patients in clinical practice as well as for developing successful therapies for these 2 groups through clinical trials. This liver failure may be the first sign of having Wilson disease. 3). Mov Disord. Saturation of concepts was determined to be adequate after the third wave of interviews (i.e. This copper overload damages these organs. Dont go near XXX, youll capture it (Patient 2). "I have trouble getting two pins, let alone all of them," he said. All concepts retrieved from the literature review were included in the preliminary WD conceptual model, with prioritized concepts in bold (Additional file 1: Fig. Impacts were reorganized from immediate and general categories into 3 conceptual categories to better reflect feedback from interviews: physical, emotional and social/functional (Fig. Among psychiatric signs/symptoms, anxiety (7.5), irritability (5.6), frustration (6), depression (8.5), frequent up and down in mood (6.2), and apathy (6) were considered salient. The diagnosis can be confirmed withblood tests measuring serum copper and ceruloplasmin, a blood protein that contains copper. E-MAIL: howard@wayflex.ro Wilson disease is a hereditary disease in which excessive amounts of copper accumulate in the body, mainly in the liver. Data were also analyzed to explore the change in the patient experience over time and to evaluate potential subgroups of patients based on symptoms reported. Patient transcripts were analyzed chronologically after each wave to assess whether concept saturation had been reached. A further important feature of this work is that the study included patients with a very large range of disease duration (from 5 to 55years since diagnosis), which allowed for coverage of concepts that are important to patients across the full disease course. Help us help you! Content validityestablishing and reporting the evidence in newly developed patient-reported outcomes (PRO) instruments for medical product evaluation: ISPOR PRO good research practices task force report: part 1eliciting concepts for a new PRO instrument. Individuals with WD experience many highly bothersome symptoms that span across multiple bodily systems, resulting in hepatic, neurological, and psychiatric impairments. The impact of WD to patients health-related quality of life (HRQoL) has not been extensively assessed. Concepts were prioritized if the higher end of the prevalence range stated in the literature was 50%. Poujois A, Woimant F, Samson S, Chaine P, Girardot-Tinant N, Tuppin P. Characteristics and prevalence of Wilsons disease: a 2013 observational population-based study in France. Qualitative research methods were used to determine the most salient concepts based on the number of patients who experience each and the average peak bother reported. WAYFLEX EUROPE USA. J Neurol Neurosurg Psychiatry. Twenty of the 74 symptoms discussed with patients were excluded from the final conceptual model because they were not endorsed by patients (unable to walk/unable to talk, difficulty eating, numbness in jaw, lower extremity pain related to swelling, skin rash, blurred vision), they would unlikely change with treatment in a clinical trial (changes in facial expression, asymmetry of face, stunted growth, spider veins), or they would not be easily captured through PRO measures (seizures, psychotic episode, mania, enlarged/swollen liver, anemia, portal vein hypertension, yellow skin [jaundice], green brown/gold rings around the eyes). Saturation of concepts was defined as the point at which no new information was forthcoming from ensuing patient interviews [19]. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Wilson's disease is an autosomal-recessive disorder of copper metabolism caused by mutations in ATP7B and associated with neurological, psychiatric, ophthalmological and hepatic manifestations. Semi-structured concept elicitation (CE) interviews were conducted with 11 patients with WD and one caregiver of one of the patients included in the interviews (a patient diagnosed at age 15 who was 22years old at the time of the interview). Bandmann O, Weiss KH, Kaler SG. By browsing this site, we may share your information with our social media partners in accordance with our Privacy Policy. Wilson disease | Copper Metabolism, Liver Damage & Genetics These medicines remove copper from the body. Im always tired. These findings also have implications for assessing treatment benefit in the context of clinical trials to support endpoint decisions relating to what is most relevant and meaningful to patients. For each concept previously experienced, patients were asked to provide a past peak bother rating using the same scale. The heterogeneity and variety of these symptoms suggests the degree of the burden placed on patients and the extent to which patients lives are negatively affected by the disease. Quality of life in patients with treated and clinically stable Wilsons disease. Individuals who tolerate the treatment and take it consistently generally enjoy good health and normal life expectancy. The second section explored the patient journey with WD, including time since diagnosis and treatment history. I could sit down, but I cantKind of like somebody hit me with a truck (Patient 7). "I'll always want to train the athletes but I'm not sure if I'll go back and do the whole film and television thing yet.". Czlonkowska A, Litwin T, Dusek P, Ferenci P, Lutsenko S, Medici V, et al. Two coders were involved in the coding of the transcripts, and inter-rater agreement (IRA) was evaluated to be maintained above 0.7. This is not like severe shaking. Howard Dell Wilson. Pediatr Transplant. Ann N Y Acad Sci. National Help Line:This support resource gives you and your loved one somewhere to turn for answers after diagnosis, helps you understand your disease, and provides you with the resources you need. Despite the copper accumulation, eyesight is not affected. Your CommunityBe an Advocacy ChampionBe a VolunteerWays to Donate, AdvocacyEventsGuest BlogLiver Disease ChampionsLiver Friendly RecipesLiver Health TipNewsPartnershipsResearchVolunteer Story, About CLF50th AnniversaryContact UsCareersPartnersBlog, STROLL For LIVERLIVERight Health ForumLIVERight Gala. 2018;4(1):21. Funct Neurol. The Canadian Liver Foundation is proud to have supported research that helped in the discovery of the Wilson disease gene. Since the gene transmitting the disease is recessively inherited, siblings of an affected individual have a 25 per cent chance of being affected. Im just tired. Wilson Disease - National Institute of Neurological Disorders and Stroke 2023 Advance Local Media LLC. Taken together, these results illustrate a more nuanced, comprehensive, and complex picture of the patient disease journey that informs treatment and disease management. The most characteristic sign is a rusty brown ring around the cornea of the eye. Patrick DL, Burke LB, Gwaltney CJ, Leidy NK, Martin ML, Molsen E, et al. It affects 1 in 30,000 individuals and may present as weakness, abdominal pain, jaundice, personality change, seizures, etc. Wilson disease is a rare genetic condition that causes a person's body to store too much of the mineral copper. In the spring of 1912, Samuel Alexander Kinnier Wilson, a young registrar at the National Hospital, Queen's Square, London, described the detailed clinical and pathologic findings of 4 patients, all of whom, he believed, had the same disease. infoneuro@muhc.mcgill.ca The toxic concentration of copper in the body must be removed. This work establishes a new understanding of what really matters to patients who experience symptoms of WD and how burdensome the different aspects of their condition can be over the course of their journey with this disease. I noticed them, but other people never noticed them (Patient 9). Fifteen impacts were found to be most salient to patients: sleep disturbance (average peak bother 6.2), worried about the future (6.1), feeling scared (6), limit in physical function (6.9), impact on social life (7), impact on ability to work (7), impact on school performance (7), made fun of/ridiculed by others (7.6), excessive daytime sleep (7.3), time burden (7.2), financial burden (7.4), embarrassed (7.2), worried about how perceived by others (8), difficulty writing (5.8), and impact on family life (5.8; Fig. "I had the same disease as (former Chicago Bears running back) Walter Payton," Dell said. Wilson disease is present at birth, but symptoms usually start between ages 5 and 35. It is also known as hepatolenticular degeneration. The U.S. Masters is typically made up of former professional athletes who still compete at high levels and is presented by USA Track and Field. The final conceptual model includes 54 symptoms (22 hepatic, 19 neurological, 13 psychiatric) and 21 impacts with salient concepts depicted in bold (Fig. These 10 signs/symptoms were tremor, headache, difficulty swallowing, yellow skin (jaundice), tendency to bleed easily, seizures, vomiting, fainting, joint pain, and joint stiffness. He also included careful descriptions of 8 similar patients from the literature, in each case pointing out the clinical features of progressive . All but 3 symptoms were mentioned by patients in Wave 1 (n=4) or Wave 2 (n=4; Additional file 1: Table S4). Sometimes I actually say weird things because Im trying to find my words, but the problem is I cant, so I have to use words around it (Patient 4). Eur J Neurol. Patients were diagnosed with WD between 5 and 55years ago. 2011;14(8):96777. For each concept currently experienced, patients were asked to provide a current peak bother rating on a scale from 0 (not at all bothered) to 10 (greatly bothered). Also, symptoms can evolve over time. USA. Previouslyas indicated by the TLRresearch has tended to focus on the neuropsychiatric aspects of the WD presentation in patients with WD, all of which may have a substantial negative impact on patients lives [8, 9, 20]. Based on the prior understanding of the disease presentation, identified signs, and symptoms (i.e., concepts) were organized into the 3 major categories: neurological, psychiatric, and hepatic. Wilson disease is an autosomal-recessive disease of copper accumulation and toxicity caused by a defect in an enzyme involved in the excretion of excess copper.