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Endocrinology, Diabetes & Metabolism... Jan 2021Wilson's disease (WD) is a rare disorder of copper metabolism usually presenting with variable liver damage and neuropsychiatric symptoms. Here we report a 39-year-old...
SUMMARY
Wilson's disease (WD) is a rare disorder of copper metabolism usually presenting with variable liver damage and neuropsychiatric symptoms. Here we report a 39-year-old Taiwanese female with late manifestation of WD presenting with gonadotroph, thyreotroph and corticotroph hypopituitarism. Molecular genetic testing revealed compound heterozygosity for two mutations in exons 12 and 14 (c.2828G>A and c.3140A>T). Copper-chelating therapy with D-penicillamine and zinc was initiated along with supplementation of hydrocortisone and L-thyroxine. Hypopituitarism resolved when urinary copper excretion returned to normal levels under copper chelation. This case should raise awareness of pituitary function in WD patients.
LEARNING POINTS
Hypopituitarism can complicate Wilson's disease (WD) and endocrinologists should be aware of it when caring for hypopituitary patients. Hepatologists should consider endocrinologic testing for hypopituitarism when WD patients present with symptoms of adrenal insufficiency, thyroid or gonadal dysfunction. Copper-chelating treatment is mandatory and may lead to the recovery of pituitary function in such patients.
PubMed: 33431708
DOI: 10.1530/EDM-20-0086 -
Deutsche Medizinische Wochenschrift... Jul 2023Wilson's disease and HFE-hemochromatosis are autosomal-recessively inherited metabolic diseases of the liver. Copper overload in case of Wilson's disease and iron...
Wilson's disease and HFE-hemochromatosis are autosomal-recessively inherited metabolic diseases of the liver. Copper overload in case of Wilson's disease and iron overload in case of hemochromatosis lead to organ damage of the liver and other organs. In order to diagnose these diseases at an early stage and introduce therapy, knowledge of the symptoms and diagnostic criteria of these diseases is important. Iron overload in hemochromatosis patients is treated with phlebotomies and copper overload in Wilson's disease patients with either chelating medications (D-penicillamine or trientine) or zinc salts. After introduction of lifelong therapy both diseases typically have a favorable disease course and further development of organ-damage can be prevented, especially with respect to liver-damage.
Topics: Humans; Hepatolenticular Degeneration; Hemochromatosis; Copper; Liver; Iron Overload
PubMed: 37364578
DOI: 10.1055/a-1871-6393 -
Pharmacological Research Jun 2024Disturbances in copper (Cu) homeostasis have been observed in diabetes and associated complications. Cu is an essential micronutrient that plays important roles in... (Review)
Review
Disturbances in copper (Cu) homeostasis have been observed in diabetes and associated complications. Cu is an essential micronutrient that plays important roles in various fundamental biological processes. For example, diabetic cardiomyopathy is associated with elevated levels of Cu in the serum and tissues. Therefore, targeting Cu may be a novel treatment strategy for diabetic complications. This review provides an overview of physiological Cu metabolism and homeostasis, followed by a discussion of Cu metabolism disorders observed during the occurrence and progression of diabetic complications. Finally, we discuss the recent therapeutic advances in the use of Cu coordination complexes as treatments for diabetic complications and their potential mechanisms of action. This review contributes to a complete understanding of the role of Cu in diabetic complications and demonstrates the broad application prospects of Cu-coordinated compounds as potential therapeutic agents.
PubMed: 38876443
DOI: 10.1016/j.phrs.2024.107264 -
World Journal of Clinical Cases May 2021Acute liver failure (ALF) can be a primary presentation of Wilson disease (WD). Mortality rates are high in WD with ALF (WDALF). Predictions of mortality in WDALF vary...
BACKGROUND
Acute liver failure (ALF) can be a primary presentation of Wilson disease (WD). Mortality rates are high in WD with ALF (WDALF). Predictions of mortality in WDALF vary by model and are sometimes contradictory, perhaps because few patients are studied or WD diagnoses are questionable.
AIM
To determine the outcomes among well-documented WDALF patients and assess mortality model performance in this cohort.
METHODS
We reviewed the medical records of our pediatric WDALF patients ( = 41 over 6-years-old, single-center retrospective study) and compared seven prognostic models (King's College Hospital Criteria, model for end-stage liver disease/pediatric end-stage liver disease scoring systems, Liver Injury Unit [LIU] using prothrombin time [PT] or international normalized ratio [INR], admission LIU using PT or INR, and Devarbhavi model) with one another.
RESULTS
Among the 41 Han Chinese patients with ALF, WD was established by demonstrating variants in 36. In 5 others, Kayser-Fleischer rings and Coombs-negative hemolytic anemia permitted diagnosis. Three died during hospitalization and three underwent liver transplantation (LT) within 1 mo of presentation and survived (7.3% each); 35 (85.4%) survived without LT when given enteral D-penicillamine and zinc-salt therapy with or without urgent plasmapheresis. Parameters significantly correlated with mortality included encephalopathy, coagulopathy, and gamma-glutamyl transpeptidase activity, bilirubin, ammonia, and serum sodium levels. Area under the receiver operating curves varied among seven prognostic models from 0.981 to 0.748 with positive predictive values from 0.214 to 0.429.
CONCLUSION
WDALF children can survive and recover without LT when given D-penicillamine and Zn with or without plasmapheresis, even after enlisting for LT.
PubMed: 34002136
DOI: 10.12998/wjcc.v9.i14.3273 -
Clinical Rheumatology Jun 2021Although lupus induced by penicillamine, the first-line medication for Wilson's disease, is well-documented, primary systematic lupus erythematosus (SLE) co-occurring... (Review)
Review
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.
Topics: Adolescent; Copper; Female; Hepatolenticular Degeneration; Humans; Lupus Erythematosus, Systemic; Magnetic Resonance Imaging; Penicillamine
PubMed: 33057918
DOI: 10.1007/s10067-020-05463-z -
Applied Materials Today Mar 2021Nitric oxide (NO) is a gasotransmitter of great significance to developing the innate immune response to many bacterial and viral infections, while also modulating... (Review)
Review
Nitric oxide (NO) is a gasotransmitter of great significance to developing the innate immune response to many bacterial and viral infections, while also modulating vascular physiology. The generation of NO from the upregulation of endogenous nitric oxide synthases serves as an efficacious method for inhibiting viral replication in host defense and warrants investigation for the development of antiviral therapeutics. With increased incidence of global pandemics concerning several respiratory-based viral infections, it is necessary to develop broad therapeutic platforms for inhibiting viral replication and enabling more efficient host clearance, as well as to fabricate new materials for deterring viral transmission from medical devices. Recent developments in creating stabilized NO donor compounds and their incorporation into macromolecular scaffolds and polymeric substrates has created a new paradigm for developing NO-based therapeutics for long-term NO release in applications for bactericidal and blood-contacting surfaces. Despite this abundance of research, there has been little consideration of NO-releasing scaffolds and substrates for reducing passive transmission of viral infections or for treating several respiratory viral infections. The aim of this review is to highlight the recent advances in developing gaseous NO, NO prodrugs, and NO donor compounds for antiviral therapies; discuss the limitations of NO as an antiviral agent; and outline future prospects for guiding materials design of a next generation of NO-releasing antiviral platforms.
PubMed: 38620577
DOI: 10.1016/j.apmt.2020.100887 -
Scientific Reports Dec 2022Smoke emissions produced by firearms contain hazardous chemicals, but little is known if their properties change depending on firearm and ammunition type and whether...
Smoke emissions produced by firearms contain hazardous chemicals, but little is known if their properties change depending on firearm and ammunition type and whether such changes affect toxicity outcomes. Pulmonary toxicity was assessed in mice exposed by oropharyngeal aspiration to six different types of smoke-related particulate matter (PM) samples; (1) handgun PM, (2) rifle PM, (3) copper (Cu) particles (a surrogate for Cu in the rifle PM) with and without the Cu chelator penicillamine, (4) water-soluble components of the rifle PM, (5) soluble components with removal of metal ions, and (6) insoluble components of the rifle PM. Gun firing smoke PM was in the respirable size range but the chemical composition varied with high levels of Pb in the handgun and Cu in the rifle smoke. The handgun PM did not induce appreciable lung toxicity at 4 and 24 h post-exposure while the rifle PM significantly increased lung inflammation and reduced lung function. The same levels of pure Cu particles alone and the soluble components from the rifle fire PM increased neutrophil numbers but did not cause appreciable cellular damage or lung function changes when compared to the negative (saline) control. Penicillamine treated rifle PM or Cu, slightly reduced lung inflammation and injury but did not improve the lung function decrements. Chelation of the soluble metal ions from the rifle fire PM neutralized the lung toxicity while the insoluble components induced the lung toxicity to the same degree as the rifle PM. The results show that different firearm types can generate contrasting chemical spectra in their emissions and that the rifle PM effects were mostly driven by water-insoluble components containing high levels of Cu. These findings provide better knowledge of hazardous substances in gun firing smoke and their potential toxicological profile.
Topics: Animals; Mice; Particulate Matter; Firearms; Penicillamine; Hazardous Substances; Chelating Agents; Water; Lung
PubMed: 36456643
DOI: 10.1038/s41598-022-24856-5 -
BMJ Case Reports Jul 2022A woman in her 30s with unclear history of cirrhosis presented to the emergency department with 8 months of worsening bilateral hand tremors, falls, depressed mood,...
A woman in her 30s with unclear history of cirrhosis presented to the emergency department with 8 months of worsening bilateral hand tremors, falls, depressed mood, altered mental status, difficulty swallowing and faecal/urinary incontinence. The patient was diagnosed with liver cirrhosis 6 years prior based on outside hospital ultrasound and liver biopsy. The hospital inpatient neurology team was promptly consulted for evaluation of worsening mental status. Kayser-Fleischer rings were visible without slit-lamp examination on clinical exam, as were prominent hand tremors and ataxia on finger-nose-finger task. Brain MRI showed increased T2/FLAIR (fluid-attenuated inversion recovery) signal within the thalami, midbrain and pons demonstrating a 'double panda sign'. Laboratory findings confirmed a diagnosis of Wilson's disease. Penicillamine and subsequent zinc therapy were initiated. Patient was eventually discharged home with plans for outpatient physical therapy and hepatology management. Two months from presentation, the patient reported significant improvement in ataxia, motor function, swallow function and incontinence.
Topics: Ataxia; Delayed Diagnosis; Female; Hepatolenticular Degeneration; Humans; Liver Cirrhosis; Penicillamine; Tremor
PubMed: 35787503
DOI: 10.1136/bcr-2021-246296 -
Clinical Anatomy (New York, N.Y.) Jul 2021Dyshomeostasis of trace elements have been implicated in the progression of Alzheimer's disease (AD), which is characterized by amyloid-β (Aβ) plaques. Trace elements... (Review)
Review
Dyshomeostasis of trace elements have been implicated in the progression of Alzheimer's disease (AD), which is characterized by amyloid-β (Aβ) plaques. Trace elements are particularly associated with the Aβ plaques. Metal-protein attenuating compounds have been developed to inhibit metals from binding to Aβ proteins, which result in Aβ termination, in the hope of improving cognitive functioning. However, there are still some contradicting reports. This review aims to first establish which trace elements are increased or decreased in the brains of Alzheimer's patients, and secondly, to review the effectiveness of clinical trials with metal-protein attenuating compounds for AD. Studies have consistently reported unchanged or increased iron, contradicting reports for zinc, decreased copper, unchanged or decreased manganese, inconsistent results for calcium, and magnesium seems to be unaffected. However, varied results have been reported for all trace elements. Clinical trials using metal-protein attenuating compounds to treat AD have also reported varied results. Copper chelators have repeatedly been used in clinical trials, even though few studies report increased brain copper levels in AD patients. Homeostasis of copper levels is important since copper has a vital role in several enzymes, such as cytochrome c, Cu/Zn superoxide dismutase and ceruloplasmin. Dyshomeostasis of copper levels can lead to increased oxidative stress and neuronal loss. Future studies should assess a variety of trace element levels in moderately and severely affected AD patients since there are contradicting reports. This review thus provides some insight into trace element alterations in the brains of individuals with AD.
Topics: Alzheimer Disease; Clioquinol; Copper; Deferoxamine; Humans; Metals; Penicillamine; Siderophores; Trace Elements
PubMed: 33580904
DOI: 10.1002/ca.23727 -
European Neurology 2022Increasing evidence has shown that oxidative stress is involved in the pathogenesis of Duchenne muscular dystrophy (DMD). Oxidative stress impairs muscle function,... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Increasing evidence has shown that oxidative stress is involved in the pathogenesis of Duchenne muscular dystrophy (DMD). Oxidative stress impairs muscle function, reduces regenerative capacity, and leads to atrophy and muscle weakness. The present study aimed to evaluate the effectiveness and safety of antioxidants in treatment of DMD patients.
METHODS
Medline, Embase, EBSCOhost, and Cochrane Library databases were searched using relevant keywords regarding DMD and antioxidants. The risk of bias for all included studies was assessed using the Cochrane risk of bias tool. The effectiveness of antioxidants in improving pulmonary function and muscle strength in DMD patients and their rate of adverse events was evaluated by meta-analysis.
RESULTS
A total of nine eligible studies were identified. Among these, two studies involving 85 patients compared idebenone with placebo. Pooled data showed a significant improvement in pulmonary function after idebenone treatment. Flavonoids- and omega 3-based compounds (FLAVOMEGA) significantly improved muscle strength. Two studies evaluated coenzyme Q10 (CoQ10) and reported clinical improvement in physical activity. The remaining four studies evaluated pentoxifylline, superoxide dismutase, vitamin E combination with penicillamine and penicillamine alone, respectively, and found no significant differences between the intervention and placebo groups, measured by pulmonary function, muscle strength, movement function, or quality of life. Most adverse events were mild, while the rates of dropout and serious adverse events were low with respect to antioxidants.
CONCLUSIONS
Idebenone appeared to be safe and effective in improving pulmonary function in DMD patients, while pentoxifylline, superoxide dismutase, penicillamine, or a combination of vitamin E with penicillamine did not show a significant therapeutic effect. CoQ10 and FLAVOMEGA might be beneficial in improving muscle strength or physical activity in DMD patients. However, additional trials with more participants are warranted in the future.
Topics: Antioxidants; Flavonoids; Humans; Muscular Dystrophy, Duchenne; Penicillamine; Pentoxifylline; Quality of Life; Superoxide Dismutase; Vitamin E
PubMed: 35697003
DOI: 10.1159/000525045