-
World Journal of Hepatology Jun 2021Wilson's disease (WD) is a rare condition caused by copper accumulation primarily in the liver and secondly in other organs, such as the central nervous system. It is a... (Review)
Review
Wilson's disease (WD) is a rare condition caused by copper accumulation primarily in the liver and secondly in other organs, such as the central nervous system. It is a hereditary autosomal recessive disease caused by a deficiency in the ATP7B transporter. This protein facilitates the incorporation of copper into ceruloplasmin. More than 800 mutations associated with WD have been described. The onset of the disease frequently includes manifestations related to the liver (as chronic liver disease or acute liver failure) and neurological symptoms, although it can sometimes be asymptomatic. Despite it being more frequent in young people, WD has been described in all life stages. Due to its fatal prognosis, WD should be suspected in all patients with unexplained biochemical liver abnormalities or neurological or psychiatric symptoms. The diagnosis is established with a combination of clinical signs and tests, including the measurement of ceruloplasmin, urinary copper excretion, copper quantification in liver biopsy, or genetic assessment. The pharmacological therapies include chelating drugs, such as D-penicillamine or trientine, and zinc salts, which are able to change the natural history of the disease, increasing the survival of these patients. In some cases of end-stage liver disease or acute liver failure, liver transplantation must be an option to increase survival. In this narrative review, we offer an overview of WD, focusing on the importance of clinical suspicion, the correct diagnosis, and treatment.
PubMed: 34239699
DOI: 10.4254/wjh.v13.i6.634 -
Best Practice & Research. Clinical... 2022Wilson's disease (WD) is an autosomal recessive genetic disorder of copper metabolism leading to liver or brain injury due to accumulation of copper. Diagnosis is based... (Review)
Review
Wilson's disease (WD) is an autosomal recessive genetic disorder of copper metabolism leading to liver or brain injury due to accumulation of copper. Diagnosis is based on: clinical features, biochemical tests including plasma ceruloplasmin concentration, 24h urinary copper excretion, copper content in the liver, and molecular analysis. Pharmacological therapy comprises chelating agents (penicillamine, trientine) and zinc salts which seem to be very effective. Still, poor compliance is a major problem. Adolescents and patients with psychiatric disorders usually have problems with adherence to treatment. As transition is a vulnerable period transition ''training'' should start before the planned transfer, preferably already in early adolescence in cooperation between adult and pediatric clinics. Response to treatment is assessed based on physical examination, normal liver function tests and monitoring of copper metabolism markers. Liver transplantation has a well-defined role in Wilsonian acute hepatic failure according to the prognostic score. The long-term survival in WD patients seems to be very similar as for the general population if disease is early diagnosed and correctly treated. WD patients with a longer delay from diagnosis to therapy and who present with neurological and psychiatric symptoms have worse quality of life.
Topics: Adolescent; Adult; Chelating Agents; Child; Copper; Hepatolenticular Degeneration; Humans; Quality of Life
PubMed: 35331405
DOI: 10.1016/j.bpg.2021.101768 -
Translational Gastroenterology and... 2021Wilson disease (WD) is rare genetic disorder that presents with varied phenotype that can at times make the diagnosis challenging. Medical treatments are available, but... (Review)
Review
Wilson disease (WD) is rare genetic disorder that presents with varied phenotype that can at times make the diagnosis challenging. Medical treatments are available, but there are still unmet needs for patients. Since life-long therapy is necessary, adherence to medical therapy and best practices for monitoring and individualizing therapy continue to evolve. Studies are ongoing that address some of these issues. In the current review we focused our attention to recent advances in the diagnosis of WD, current medical treatments, future potential therapies and treatment monitoring. We include discussion of new methodology for detection and quantitation of ophthalmologic signs of WD, new brain imaging modalities for early detection of neurologic involvement in patients and potential new diagnostic methodology using blood samples that may be applicable to newborn screening and adult disease diagnosis. In addition, there are new strategies aimed at improving adherence and outcomes with currently available therapies, including once daily chelation dosing and discussion of the efficacy of different zinc salt compounds. With respect to new therapies with different mechanisms of action, we discuss studies on Bis-choline tetrathiomolybdate (TTM) in patients, pre-clinical studies of a novel chelator methanobactin and other animal studies exploring cures for WD with gene therapy using adeno-associated vectors (AAVs) that introduce into liver cells. There are also promising advances in the more accurate measurement of non-ceruloplasmin bound copper and exchangeable copper in the circulation which would potentially help with monitoring and individualization of treatment and possibly play a role in future disease diagnosis.
PubMed: 33824925
DOI: 10.21037/tgh-2020-02 -
Annals of Translational Medicine Mar 2021Dermatomyositis (DM) is an autoimmune disease that affects the skin, lungs, and muscle. Although the pathogenesis of DM is not completely understood, several... (Review)
Review
Dermatomyositis (DM) is an autoimmune disease that affects the skin, lungs, and muscle. Although the pathogenesis of DM is not completely understood, several environmental triggers have been linked to DM onset or flare. This article specifically examines the effects of herbal supplements, drugs, infections, ultraviolet (UV) radiation, and environmental pollutants on the onset or exacerbation of DM. Herbal supplements such as , , , , and Alfalfa have been implicated and are frequently used in health foods. Medications such as hydroxyurea, TNF-α inhibitors, immune checkpoint inhibitors (ICI), and penicillamine, as well as certain viral infections, such as parvovirus B19, coxsackie virus, polyomavirus, Epstein-Barr virus (EBV), hepatitis, influenza, and human immunodeficiency viruses (HIV) have been associated with DM onset. Bacterial infections and vaccinations have also been linked to the development of DM. Additional environmental factors, including UV radiation and air pollutants, such as silica, biological/mineral dust, and particulate air matter from vehicle and industrial emissions, may also play a role in DM pathogenesis. Overall, there is general agreement that an autoimmune attack of the skin, muscle, and lungs in DM can be triggered by various environmental factors and warrants further investigation.
PubMed: 33842655
DOI: 10.21037/atm-20-3719 -
Mini Reviews in Medicinal Chemistry 2020The thiol (-SH) functional group is found in a number of drug compounds and confers a unique combination of useful properties. Thiol-containing drugs can reduce radicals... (Review)
Review
The thiol (-SH) functional group is found in a number of drug compounds and confers a unique combination of useful properties. Thiol-containing drugs can reduce radicals and other toxic electrophiles, restore cellular thiol pools, and form stable complexes with heavy metals such as lead, arsenic, and copper. Thus, thiols can treat a variety of conditions by serving as radical scavengers, GSH prodrugs, or metal chelators. Many of the compounds discussed here have been in use for decades, yet continued exploration of their properties has yielded new understanding in recent years, which can be used to optimize their clinical application and provide insights into the development of new treatments. The purpose of this narrative review is to highlight the biochemistry of currently used thiol drugs within the context of developments reported in the last five years. More specifically, this review focuses on thiol drugs that represent the standard of care for their associated conditions, including N-acetylcysteine, 2,3-meso-dimercaptosuccinic acid, British anti-Lewisite, D-penicillamine, amifostine, and others. Reports of novel dosing regimens, delivery strategies, and clinical applications for these compounds were examined with an eye toward emerging approaches to address a wide range of medical conditions in the future.
Topics: Animals; Humans; Molecular Structure; Oxidative Stress; Sulfhydryl Compounds
PubMed: 31746294
DOI: 10.2174/1389557519666191119144100 -
Archives of Toxicology Jun 2020Arsenic (As) is widely used in the modern industry, especially in the production of pesticides, herbicides, wood preservatives, and semiconductors. The sources of As... (Review)
Review
Arsenic (As) is widely used in the modern industry, especially in the production of pesticides, herbicides, wood preservatives, and semiconductors. The sources of As such as contaminated water, air, soil, but also food, can cause serious human diseases. The complex mechanism of As toxicity in the human body is associated with the generation of free radicals and the induction of oxidative damage in the cell. One effective strategy in reducing the toxic effects of As is the usage of chelating agents, which provide the formation of inert chelator-metal complexes with their further excretion from the body. This review discusses different aspects of the use of metal chelators, alone or in combination, in the treatment of As poisoning. Consideration is given to the therapeutic effect of thiol chelators such as meso-2,3-dimercaptosuccinic acid, sodium 2,3-dimercapto-1-propanesulfonate, 2,3-dimercaptopropanol, penicillamine, ethylenediaminetetraacetic acid, and other recent agents against As toxicity. The review also considers the possible role of flavonoids, trace elements, and herbal drugs as promising natural chelating and detoxifying agents.
Topics: Animals; Antidotes; Arsenic Poisoning; Arsenicals; Chelating Agents; Environmental Exposure; Environmental Pollutants; Humans; Plant Preparations; Risk Assessment; Treatment Outcome
PubMed: 32388818
DOI: 10.1007/s00204-020-02739-w -
Animals : An Open Access Journal From... Oct 2022We assessed the protective effects of Gandouling (GDL) on copper sulfate (CuSO4)-induced heart injuries in Sprague−Dawley rats, which were randomly divided into the...
We assessed the protective effects of Gandouling (GDL) on copper sulfate (CuSO4)-induced heart injuries in Sprague−Dawley rats, which were randomly divided into the control, CuSO4, GDL + CuSO4 and penicillamine + CuSO4 groups. The rats received intragastric GDL (400 mg/kg body weight) once per day for 42 consecutive days after 56 days of CuSO4 exposure, and penicillamine was used as a positive control. The levels of plasma inflammatory cytokines (IMA, hFABP, cTn-I and BNP) were determined using the enzyme-linked immunosorbent assay. The histopathological symptoms were evaluated using hematoxylin and eosin staining and transmission electron microscopy. To determine the underlying mechanism, Western blotting was conducted for the detection of the heme oxygenase 1 (HO-1) expression. The results revealed that GDL supplementation alleviated the histopathological symptoms of the rat heart tissue, promoted Cu excretion to attenuate impairment, and significantly decreased inflammatory cytokine levels in the plasma (p < 0.01). In addition, GDL increased the HO-1 expression in the rat hepatic tissue. The protective effect of GDL on the heart was superior to that of penicillamine. Overall, these findings indicate that GDL alleviates hepatic heart injury after a Cu overaccumulation challenge, and GDL supplements can be beneficial for patients with Wilson’s disease.
PubMed: 36230444
DOI: 10.3390/ani12192703 -
Digestive and Liver Disease : Official... Dec 2019
Topics: Adult; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Autoimmune Diseases; Autoimmunity; Chelating Agents; Clinical Deterioration; Fatal Outcome; Female; Hepatolenticular Degeneration; Humans; Immunologic Tests; Patient Care Management; Penicillamine; Renal Insufficiency
PubMed: 31669076
DOI: 10.1016/j.dld.2019.08.025 -
World Journal of Hepatology Oct 2023Wilson disease is an autosomal recessive disorder affecting the ATP7B gene located on chromosome 13q. This leads to copper deposition in various organs, most importantly... (Review)
Review
Wilson disease is an autosomal recessive disorder affecting the ATP7B gene located on chromosome 13q. This leads to copper deposition in various organs, most importantly in the liver and brain. The genetic mutations are vast, well reported in the West but poorly documented in developing countries. Hence the diagnosis is made with a constellation of clinico-laboratory parameters which have significant overlap with other liver diseases and often pose a significant dilemma for clinicians. Diagnostic scoring systems are not fool-proof. The availability and affordability of chelators in developing countries impact the drug compliance of patients. While D-penicillamine is a potent drug, its side effects lead to drug discontinuation. Trientine is cost-prohibitive in developing countries. There is no single test to assess the adequacy of chelation. Exchangeable urinary copper is an essential upcoming diagnostic and prognostic tool. In the presence of cirrhosis, hypersplenism clouds the assessment of myelosuppression of drugs. Similarly, it may be difficult to distinguish disease tubulopathy from drug-induced glomerulonephritis. Neurological worsening due to chelators may appear similar to disease progression. Presentation as fulminant hepatic failure requires rapid workup. There is a limited window of opportunity to salvage these patients with the help of plasmapheresis and other liver-assisted devices. This review addresses the challenges and clinical dilemmas faced at beside in developing countries.
PubMed: 37970614
DOI: 10.4254/wjh.v15.i10.1109 -
Medicine Feb 2023Hepatolenticular degeneration, also known as Wilson disease (WD), is an autosomal recessive inherited disease characterized by copper metabolism, which has complex...
RATIONALE
Hepatolenticular degeneration, also known as Wilson disease (WD), is an autosomal recessive inherited disease characterized by copper metabolism, which has complex clinical manifestations, and mainly including liver and nervous system lesions. Pregnancy combined with WD is extremely harmful to mothers and children, with high miscarriage rates, and premature birth rates and perinatal mortality.
PATIENT CONCERNS
Here we introduced the basic information of 4 pregnant women with WD. The first pregnant woman had a 16-year history of WD, stopped taking penicillamine 1 year before pregnancy. The second woman had a 3-year history of WD and was taking penicillamine regularly, unintended pregnancy occurred 1 month after stopping the drug. The third woman had a history of WD for 5 years with penicillamine treatment. The 4th woman was found to have WD due to repeated missed miscarriage with abnormal liver function, after which penicillamine was regularly taken. Fortunately, she was pregnant again a year later.
DIAGNOSES
The pregnant women in case 1 and case 2 were diagnosed with decompensated cirrhosis with coagulation dysfunction during pregnancy. The pregnant woman in case 3 was found to have liver cirrhosis by ultrasound, and the pregnant woman in case 4 did not have liver abnormalities during pregnancy.
INTERVENTIONS
The pregnant woman in case 1 began to take copper-removing drugs and take a low-copper diet after finding the aggravation of the disease in the early stage of pregnancy, and had good compliance during pregnancy. The pregnant woman in case 2 had poor compliance during pregnancy and did not receive any treatment. The pregnant woman in case 3 refused to use copper elimination drugs during pregnancy, but took a low copper diet. The pregnant woman in case 4 had good compliance during pregnancy, and she was treated with drugs and low copper diet during the whole pregnancy.
OUTCOMES
Three of the four pregnant women got a healthy baby but premature, and only the pregnant woman in case 2 had spontaneous abortion at 25 weeks.
LESSONS
After comprehensive monitoring and multidisciplinary management of professional medical staff before and after pregnancy, WD pregnant women still have the opportunity to obtain a better pregnancy outcome and improve quality of life.
Topics: Child; Pregnancy; Female; Humans; Hepatolenticular Degeneration; Copper; Abortion, Spontaneous; Quality of Life; Penicillamine
PubMed: 36800617
DOI: 10.1097/MD.0000000000032968