Ferroptosis, an iron-dependent form of cell death, plays a crucial role in the progression of liver injury in Wilson\'s disease (WD). Gandouling (GDL) has emerged as a potential therapeutic agent for preventing and treating liver injury in WD. However, the precise mechanisms by which GDL mitigates ferroptosis in WD liver injury remain unclear. In this study, we discovered that treating Toxic Milk (TX) mice with GDL effectively decreased liver copper content, corrected iron homeostasis imbalances, and lowered lipid peroxidation levels, thereby preventing ferroptosis and improving liver injury. Bioinformatics analysis and machine learning algorithms identified Hspb1 as a pivotal regulator of ferroptosis. GDL treatment significantly upregulated the expression of HSPB1 and its upstream regulatory factor HSF1, thereby activating the HSF1/HSPB1 pathway. Importantly, inhibition of this pathway by NXP800 reversed the protective effects of GDL on ferroptosis in the liver of TX mice. In conclusion, GDL shows promise in alleviating liver injury in WD by inhibiting ferroptosis through modulation of the HSF1/HSPB1 pathway, suggesting its potential as a novel therapeutic agent for treating liver ferroptosis in WD.

Wilson\'s disease is a genetic neurometabolic disorder affecting copper metabolism in the body. It occurs due to mutations in the ATP7B gene. Here, we report a case of a 12-year-old boy, born out of a second-degree consanguineous marriage, who presented with complaints of jaundice for the past one year, poor scholastic performance, and behavioral abnormalities for the past one month. There was a history of multiple suicides in the maternal family, and liver disorder in the maternal uncle. Various examinations revealed jaundice, Kayser-Fleischer ring in eyes, and dystonia of the extremities with hepatosplenomegaly. Copper studies were inconclusive, and neuroimaging showed characteristic findings specific for Wilson\'s disease. The child was treated with a low-copper diet, vitamin K, oral zinc acetate, oral D-penicillamine, trihexyphenidyl, baclofen, clonazepam, and propranolol.

Wilson\'s disease is a rare genetic disorder characterized by abnormal copper metabolism due to mutations in the ATP-7B gene. This case report details the presentation of a 14-year-old male child exhibiting severe generalized dystonia, rigidity, myoclonic jerks, dysarthria, and excessive salivary drooling. During ophthalmic examination, Kayser-Fleischer rings were identified. Symmetrical hyperintensities in cortical and subcortical areas, including the basal ganglia and brainstem, were noted on brain magnetic resonance imaging (MRI). Additionally, diffusion restriction in the bilateral fronto-parietal region was observed. The diagnosis of Wilson\'s disease was confirmed through further diagnostic assessments, such as serum ceruloplasmin levels and urine copper excretion. Treatment was initiated with penicillamine, anticonvulsants, and supportive measures, resulting in partial recovery after a three-month follow-up period. This case emphasizes the significance of identifying atypical MRI brain findings in Wilson\'s disease, which aids in early diagnosis and appropriate management to prevent irreversible neurological damage.

Wilson\'s disease (WD) is a rare inherited disease due to the mutation of the ATP7B gene, resulting in impaired hepatic copper excretion and its pathological accumulation in various organs such as the liver, the nervous system, or the kidneys. Whereas liver failure and neuropsychiatric disorders are the most common features, less is known about the renal complications. We conducted a review of the literature to define the characteristics and pathophysiology of kidney involvement during WD. This review shed light on strong evidence for direct copper toxicity to renal tubular cells. Excessive tubular copper accumulation might present with various degrees of tubular dysfunction, ranging from mild hydroelectrolytic and acid-base disorders to complete Fanconi syndrome. Proximal and distal renal tubular acidosis also favors development of nephrolithiasis, nephrocalcinosis, and bone metabolism abnormalities. Indirect complications might involve renal hypoperfusion as occurs in hepatorenal or cardiorenal syndrome, but also tubular casts\' formation during acute hemolysis, rhabdomyolysis, or bile cast nephropathy. Acute kidney failure is not uncommon in severe WD patients, and independently increases mortality. Finally, specific and long-term therapy by D-penicillamin, one of the most efficient drugs in WD, can cause glomerular injuries, such as membranous nephropathy, minimal-change disease, and, rarely, severe glomerulonephritis. Altogether, our study supports the need for interdisciplinary evaluation of WD patients involving nephrologists, with regular monitoring of tubular and glomerular functions, to provide adequate prevention of renal and bone involvement.

BACKGROUND: Wilson\'s disease (WD) often leads to liver fibrosis and cirrhosis, and early diagnosis of WD cirrhosis is essential. Currently, there are few non-invasive prediction models for WD cirrhosis. The purpose of this study is to non-invasively predict the occurrence risk of compensated WD cirrhosis based on ultrasound imaging features and clinical characteristics.
METHODS: A retrospective analysis of the clinical characteristics and ultrasound examination data of 102 WD patients from November 2018 to November 2020 was conducted. According to the staging system for WD liver involvement, the patients were divided into a cirrhosis group (n = 43) and a non-cirrhosis group (n = 59). Multivariable logistic regression analysis was used to identify independent influencing factors for WD cirrhosis. A nomogram for predicting WD cirrhosis was constructed using R analysis software, and validation of the model\'s discrimination, calibration, and clinical applicability was completed. Due to the low incidence of WD and the small sample size, bootstrap internal sampling with 500 iterations was adopted for validation to prevent overfitting of the model.
RESULTS: Acoustic Radiation Force Impulse (ARFI), portal vein diameter (PVD), and serum albumin (ALB) are independent factors affecting WD cirrhosis. A nomogram for WD cirrhosis was constructed based on these factors. The area under the ROC curve (AUC) of the model\'s predictive ability is 0.927 (95% CI: 0.88-0.978). As demonstrated by 500 Bootstrap internal sampling validations, the model has high discrimination and calibration. Clinical decision curve analysis shows that the model has high clinical practical value. ROC curve analysis of the model\'s rationality indicates that the model\'s AUC is greater than the AUC of using ALB, ARFI, and PVD alone.
CONCLUSIONS: The nomogram model constructed based on ARFI, PVD, and ALB can serve as a non-invasive tool to effectively predict the risk of developing WD cirrhosis.

BACKGROUND: Wilson\'s disease (WD) is an autosomal recessive disorder in which copper (Cu) accumulates in organs, particularly in the liver and central nervous system. This study aimed to investigate the prevalence, incidence, and treatment patterns of WD patients in Korea.
METHODS: National Health Insurance System (NHIS) claims data from 2010 to 2020 were analyzed. patients with WD as a primary or additional diagnosis at least once were identified using the International Classification of Diseases (ICD)-10 disease code E83.0 and a record for a registration program for rare intractable diseases in Korea.
RESULTS: The average age- and sex-adjusted prevalence and incidence of WD between 2010 and 2020 were 3.06/100,000 and 0.11/100,000, respectively. The mean age of the patients with newly diagnosed WD was 21.0 ± 15.9 years. Among the 622 WD incident cases during the study period, 19.3% of the patients had liver cirrhosis and 9.2% had received liver transplantation. Psychological and neurological diseases were present in 40.7% and 48.1% of the patients, respectively. Regarding the diagnosis of WD, liver biopsy was performed in only 51.6% of new cases. D-penicillamine, trientine, or zinc were prescribed in 81.5% of the incident cases, and the treatment uptake rates decreased with increasing age.
CONCLUSIONS: The prevalence of WD in Korea is 3.06/100,000 and approximately 1,800 patients use medical services annually. A significant proportion of patients are diagnosed at the cirrhotic stage and not treated with Cu-chelating therapeutics, suggesting the need for early diagnosis and adequate treatment to improve prognosis.

暂无摘要。

Wilson\'s disease is a genetic disorder of copper metabolism that primarily manifests with hepatic and neurological features. Kayser-Fleischer rings (KF rings) are pathognomonic of Wilson\'s disease and helps in establishing its diagnosis.

Wilson\'s disease (WD) is a genetic disorder that primarily leads to the pathological accumulation of copper (Cu) in the liver, causing an abnormal increase in reactive oxygen species (ROS). The prevailing clinical therapy for WD involves lifelong use of Cu chelation drugs to facilitate Cu excretion in patients. However, most available drugs exert severely side-effects due to their non-specific excretion of Cu, unsuitable for long-term use. In this study, we construct a prochelator that enables precise and controlled delivery of Cu chelator drugs to the liver in WD model, circumventing toxic side effects on other organs and normal tissues. This innovative prochelator rapidly releases the chelator and the fluorescent molecule methylene blue (MB) upon activation by ROS highly expressed in the liver of WD. The released chelator coordinates with Cu, efficiently aiding in Cu removal from the body and effectively inhibiting the pathological progression of WD.

This case report describes the atypical presentation of Wilson\'s disease in a 17-year-old male with sickle cell trait AS pattern. The patient initially presented with fever, generalized weakness, and joint pain, leading to an inconclusive diagnosis and unsuccessful initial treatment. A comprehensive re-evaluation revealed vitamin-A deficiency, adenoid hypertrophy, splenomegaly, and acalculous cholecystitis. Elevated copper levels in the 24-hour urine test confirmed the diagnosis of Wilson\'s disease. Treatment was modified to include amikacin, prednisolone, and Zinconia®, with analgesics for joint pain management. This case emphasizes the need for a thorough diagnostic approach and consideration of overlapping conditions in complex presentations, contributing to improved patient outcomes.