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.

UNASSIGNED: Wilson\'s disease (WD) is an inherited disorder characterized by impaired biliary excretion of copper and excessive copper accumulation in multiple organs, primarily leading to hepatic, neurological, and psychiatric manifestations. The coexistence of WD and systemic lupus erythematosus (SLE) has rarely been reported, posing challenges in accurately diagnosing these two conditions because of overlapping clinical symptoms.
UNASSIGNED: We presented the case of a 17-year-old girl initially suspected of having SLE due to positive anti-nuclear antibodies and lupus anticoagulants, decreased platelet count, hypocomplementemia, and pleural effusion. However, the patient also exhibited an unusual manifestation of decompensated liver cirrhosis, which is not typical of SLE. Further investigation revealed low serum ceruloplasmin levels, high 24-h urine copper levels, the presence of Kayser-Fleischer rings, and a compound heterozygous mutation in the ATP7B gene, confirming the diagnosis of WD.
UNASSIGNED: The co-occurrence of WD and SLE poses a significant diagnostic challenge, often leading to misdiagnosis and delayed diagnosis. Therefore, in patients with well-controlled SLE presenting with unexplained liver fibrosis, neurological involvement, or psychiatric symptoms, it is crucial to consider the possibility of WD. However, further studies are required to elucidate the underlying pathophysiological mechanisms.

UNASSIGNED: Traditional Chinese medicine (TCM) is widely used in the clinical treatment of hepatolenticular degeneration (HLD) and liver fibrosis (LF). In the present study, the curative effect was assessed using meta-analysis. The possible mechanism of TCM against LF in HLD was investigated using network pharmacology and molecular dynamics simulation.
UNASSIGNED: For literature collection, we searched several databases, including PubMed, Embase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure (CNKI), VIP Database for Chinese Technical Periodicals (VIP) and Wan Fang database until February 2023, and the Review Manager 5.3 was used to analyze the data. Network pharmacology and molecular dynamics simulation were used to explore the mechanism of TCM in treating LF in HLD.
UNASSIGNED: The results of the meta-analysis revealed that the addition of Chinese herbal medicine (CHM) in treating HLD resulted in a higher total clinical effective rate than western medicine alone [RR 1.25, 95% CI (1.09, 1.44), p = 0.002]. It not only has a better effect on liver protection [Alanine aminotransferase: SMD = -1.20, 95% CI (-1.70, -0.70), p < 0.00001; Aspartate aminotransferase: SMD = -1.41, 95% CI (-2.34, -0.49), p = 0.003; Total bilirubin: SMD = -1.70, 95% CI (-3.36, -0.03), p = 0.05] but also had an excellent therapeutic effect on LF through four indexes [Hyaluronic acid: SMD = -1.15, 95% CI (-1.76, -0.53), p = 0.0003; Procollagen peptide III: SMD = -0.72, 95% CI (-1.29, -0.15), p = 0.01; Collagen IV: SMD = -0.69, 95% CI (-1.21, -0.18), p = 0.008; Laminin: SMD = -0.47, 95% CI (-0.95, 0.01), p = 0.06]. Concurrently, the liver stiffness measurement decreased significantly [SMD = -1.06, 95% CI (-1.77, -0.36), p = 0.003]. The results of network pharmacological experiments and molecular dynamics simulation indicate that the three high-frequency TCMs (Rhei Radix Et Rhizoma-Coptidis Rhizoma-Curcumae Longae Rhizoma, DH-HL-JH) primarily act on the core targets (AKT1, SRC, and JUN) via the core components (rhein, quercetin, stigmasterol, and curcumin), regulate the signal pathway (PI3K-Akt, MAPK, EGFR, and VEGF signaling pathways), and play a role of anti-LF.
UNASSIGNED: Meta-analysis indicates that TCM is beneficial in treating HLD patients and improving LF. The present study successfully predicts the effective components and potential targets and pathways involved in treating LF for the three high-frequency CHMs of DH-HL-JH. The findings of the present study are hoped to provide some evidence support for clinical treatment.
UNASSIGNED: https://www.crd.york.ac.uk/PROSPERO, identifier: CRD42022302374.

BACKGROUND: Wilson\'s disease (WD) is a rare inherited disorder that leads to copper accumulation in the liver, brain, and other organs. WD is prevalent worldwide, with an occurrence of 1 per 30,000 live births. Currently, there is no gold standard diagnostic test for WD. The objective of this systematic review is to determine the diagnostic accuracy for WD of three biochemical tests, namely hepatic copper, 24-hour urinary copper, and ceruloplasmin using the Leipzig criteria.
METHODS: Adhering to PRISMA guidelines, databases including PubMed/MEDLINE, CINAHL Plus, Web of Science, and Cochrane were searched. Studies that comprised of confirmed or suspected WD along with normal populations were included with adult and pediatric group. The sensitivity, specificity, negative predictive value and positive predictive value were computed using RevMan 5.4.
RESULTS: Nine studies were included. The best practice evidence for 24-hour urinary copper test ranged from a cutoff value of 0.64-1.6 μmol/24 h (N = 268; sensitivity = 75.6%, specificity = 98.3%). Hepatic copper test was optimally cutoff based on the ROC curve analysis at 1.2 μmol/g yielding a power of 96.4% sensitivity and 95.4% specificity (N = 1,150); however, the tried and tested 4 μmol/g cutoff, with 99.4% sensitivity and 96.1% specificity, is more widely accepted. The ceruloplasmin test cutoff value was found to be ranging from 0.14 to 0.2 g/L (N = 4,281; sensitivity = 77.1%-99%, specificity = 55.9%-82.8%).
CONCLUSIONS: This paper provides a large-scale analysis of current evidence pertaining to the biochemical diagnosis of WD employing the Leipzig criteria. The laboratory values are typically based on specific subgroups based on age, ethnicity, and clinical subgroups. The findings of this systematic review must be used with caution, given the over- or under-estimation of the index tests.

The most common glomerulonephritis seen in the world is immunoglobulin A nephropathy (IgAN). It can be primary or secondary associated with various conditions like Chronic Liver disease, Crohn\'s disease, neoplasms, etc. However, IgAN secondary to Wilson\'s disease is very rare. A 9 year old boy presented with gross hematuria and proteinuria. He had a history of recurrent jaundice in the past. Ultrasonography (USG) whole abdomen showed altered echotexture of the liver with normal-sized kidneys. An extended workup for liver disease was done, and the diagnosis of Wilson\'s disease was confirmed with decreased serum ceruloplasmin levels, increased urinary copper, and the Kayser-Fleischer ring. Urine routine microscopy showed numerous red blood cells, few red blood cell casts, and mild proteinuria. Renal biopsy showed IgAN. The patient was started on D-penicillamine. On follow-up at 3 months, he showed complete resolution of proteinuria and hematuria. Thus, we suggest that Wilson\'s disease should be considered as one of the causes of secondary IgAN in pediatric patients with hematuria, proteinuria with liver dysfunction.

In Wilson\'s disease (WD), copper accumulation can result in neurological manifestations, particularly extrapyramidal symptoms. There are some data that the autonomic nervous system (ANS) may also be affected, and we aimed to systematically review available studies evaluating ANS dysfunction in WD.
We conducted a systematic review of the literature using the PubMed database (up to 31st August 2020), with search terms including \"autonomic\" and \"function\" and \"Wilson\'s disease\".
Fourteen studies, including 297 patients with neurological, hepatic or psychiatric forms of WD were retrieved. The most frequent methods used for ANS evaluation were orthostatic tests, which were performed in seven studies, with a number of other tests less frequently used. The incidence of ANS abnormalities ranged from ~8% to 79.2%, depending on the evaluation method. ANS abnormalities in patients with WD were often clinically asymptomatic. The features of dysautonomia were more common among patients with neurological symptoms and ANS abnormalities were more common in patients with severe brain injury. Studies confirmed both sympathetic and parasympathetic ANS impairment. The pathophysiology of ANS damage was not clear but may result from central, peripheral nervous system and direct cardiac involvement. Clear improvements were observed in four studies after anti-copper therapy initiation.
Both sympathetic and parasympathetic divisions of the ANS may be affected in WD. The observed ambiguities regarding ANS abnormalities in WD patients may arise from small study groups, differences in methodology, and a lack of comprehensive ANS evaluation; however, the results indicate that further studies are warranted.

Background: Wilson\'s disease (WD) is a rare condition; its diagnosis is challenging owing to a wide spectrum of ATP7B genotypes and variable clinical phenotypes, along with environmental factors. Few cases of WD with presentation of skin lesions and acute neurovisceral symptoms have been reported in the literature. To our knowledge, this is the first reported case of WD with an uncommon ATP7B gene mutation and rare symptoms of photosensitivity, sensation abnormality, and skin eruption occurring in a 19-year-old woman. Case presentation: We report the case of a 19-year-old woman with WD presenting with liver failure, skin manifestations, and acute neurovisceral symptoms.The rare mutation in intron 1 of ATP7B (c.51+2T > G) was further confirmed by gene sequencing. The patients\' symptoms improved after administration of penicillamine and zinc therapy combined with plasma exchange. She received long-term penicillamine treatment, and her liver function was within the normal range at 1 year after discharge. However, she underwent liver transplantation at 1.5 years after discharge. Conclusions: We present a case of WD with a novel ATP7B gene mutation that may serve as a reference to generalists and specialists in hepatology or neurology of the rare clinical characteristics of WD, to prevent misdiagnosis and aid in the early diagnosis and treatment of the condition.

Wilson\'s disease (WD) is a rare genetic disorder of copper metabolism that often manifests several clinical signs at the time of diagnosis. Typically it affects the liver in the early stages of the disease course and tends to show neuropsychiatric involvement in the later stages. Early diagnosis of WD holds a prognostic value, and an atypical presentation of the disease adds complexities in diagnosis. Even though we need to consolidate further the treatment guidelines for managing psychiatric and neurological symptoms optimally in the patients of WD, identifying signs at the early stages of the disease is crucial to avoid its detrimental effects on the human body. In this case presentation, a patient with no family history of psychiatric condition showed an early onset of neuropsychiatric symptoms without any other clinical signs of WD. Through this clinical case, we emphasize the importance of ruling out WD in patients that predominantly presents with psychiatric symptoms as a lone symptom. It also highlights the possible diagnostic value and significance of the ceruloplasmin level in identifying WD disease in early stages, when other clinical signs are absent, including liver abnormalities.

Prescribing d-penicillamine for Wilson\'s disease must be accompanied by vigilant monitoring, including a complete blood cell count with differential. For most, this should occur once or twice weekly during the first month of therapy and during periods of dose escalation, then every two weeks for six additional months, then monthly.

Wilson\'s disease (WD) is a rare autosomal recessive inherited disorder of chronic copper toxicosis. Currently, Chinese herbal medicines (CHM) is widely used for WD. Here, we conducted an updated systematic review to investigate the efficacy and safety of CHM for WD and its possible mechanisms. Randomized-controlled clinical trials (RCTs), which compared CHM with Western conventional medicine or placebo for WD, were searched in six databases from inception to July 2017. The methodological quality was assessed using 7-item criteria from the Cochrane\'s collaboration tool. All the data were analyzed using Rev-Man 5.3 software. Eighteen studies involving 1,220 patients were identified for the final analyses. A score of study quality ranged from 2/7 to 4/7 points. Meta-analyses showed that CHM could significantly increase 24-h urinary copper excretion and improve liver function and the total clinical efficacy rate for WD compared with control (p < 0.05). Additionally, CHM was well tolerated in patients with WD. The underlying mechanisms of CHM for WD are associated with reversing the ATP7B mutants, exerting anti-oxidation, anti-inflammation, and anti-hepatic fibrosis effects. In conclusion, despite the apparent positive results, the present evidence supports, to a limited extent because of the methodological flaws and CHM heterogeneity, that CHM paratherapy can be used for patients with WD but could not be recommended as monotherapy in WD. Further rigorous RCTs focusing on individual CHM formula for WD are warranted.