scholarly journals Wilson Disease: Canadian Perspectives on Presentation And Outcomes from an Adult Ambulatory Setting

2012 ◽  
Vol 26 (6) ◽  
pp. 333-339 ◽  
Author(s):  
A Moores ◽  
SH Fox ◽  
AE Lang ◽  
GM Hirschfield
Keyword(s):  
Basal Ganglia ◽  
Wilson Disease ◽  
Copper Metabolism ◽  
Retrospective Chart Review ◽  
Complete Recovery ◽  
Initial Therapy ◽  
Ambulatory Setting ◽  
Venous Flow ◽  
Variceal Bleed ◽  
Urinary Copper

BACKGROUND: Wilson disease (WD) is a rare disorder of copper metabolism.OBJECTIVE: To describe the authors’ clinical experience with a cohort of 48 adult patients followed in an ambulatory setting.METHODS: A retrospective chart review of patients with a diagnosis of WD was performed.RESULTS: Fifty-nine charts were identified and 11 were excluded on further review. At diagnosis, 14 patients were asymptomatic, with 13 hepatic, 15 neurological and six mixed hepatic/neurological presentations. Ceruloplasmin levels were low (<0.20 g/L) in 94%, and 24 h urinary copper levels high (>0.60 μmol/L) in 95% of cases. D-penicillamine was the most common initial therapy (48%), with zinc the most common at review (65%). Overall, biopsy and ultrasound reports documented cirrhosis in 53%. Portal hypertension, defined as splenomegaly (>12.0 cm), reversed portal venous flow on ultrasound or varices/gastropathy on endoscopy was seen in 63%. At last review, 39% had elevated aspartate aminotransferase (>34 U/L) and/or alanine aminotransferase levels (>40 U/L). One death and one transplant occurred, while three patients had encephalopathy, two became jaundiced, two developed ascites and one experienced variceal bleed. Of 21 neurological presenting patients, 14 improved compared with baseline, with four making almost complete recovery. Eleven patients experienced documented episodes of neurological decline, including four with non-neurological presentation. Diagnostic magnetic resonance imaging showed basal ganglia (64%), brainstem (64%) abnormalities and atrophy (36%); follow-up showed basal ganglia lesions (50%) and atrophy (55%).CONCLUSION: WD is a diverse chronic disease with generally favourable outcomes for patients who respond to initial therapy, which can be managed predominantly in an ambulatory setting.

Biochemical and molecular characterisation of neurological Wilson disease

2018 ◽  
Vol 55 (9) ◽  
pp. 587-593 ◽  
Author(s):  
Go Hun Seo ◽  
Yoon-Myung Kim ◽  
Seak Hee Oh ◽  
Sun Ju Chung ◽  
In Hee Choi ◽  
...  
Keyword(s):  
Wilson Disease ◽  
Age At Onset ◽  
Copper Metabolism ◽  
Favourable Outcome ◽  
Treatment Needs ◽  
Serum Ceruloplasmin ◽  
Urinary Copper ◽  
Genetic Features ◽  
Distinct Disease ◽  
Serum Aspartate Aminotransferase

BackgroundTo identify biochemical and genetic features that characterise neurological Wilson disease as a distinct disease subgroup.MethodsDetailed biochemical profiles and genotypic characteristics of neurological (86 patients) and hepatic subgroups (233 patients) from 368 unrelated Korean families were analysed.ResultsCompared with patients in the hepatic subgroup, patients in the neurological subgroup had a later age at onset, a higher proportion with Kayser-Fleischer rings and higher serum creatinine levels, and a lower proportion with favourable outcome (62% vs 80%, P<0.016). At diagnosis, the neurological subgroup had lower serum ceruloplasmin (3.1±2.1 mg/dL vs 4.2±3.2 mg/dL, P<0.001), total copper (26.4±13.8 µg/dL vs 35.8±42.4 µg/dL, P=0.005), free copper (17.2±12.5 µg/dL vs 23.5±38.2 µg/dL, P=0.038) and urinary copper (280.9±162.9 µg/day vs 611.1±1124.2 µg/day, P<0.001) levels. Serum aspartate aminotransferase, alanine aminotransferase, gamma glutamyltransferase and total bilirubin levels, as well as prothrombin time, were also lower in the neurological subgroup. Liver cirrhosis was more common but mostly compensated in the neurological subgroup. Frameshift, nonsense or splice-site ATP7B mutations and mutations in transduction or ATP hinge domains (2.4% vs 23.1%, P=0.006) were less common in the neurological subgroup.ConclusionThe neurological subgroup had distinct clinical, biochemical and genetic profiles. Further studies are required to identify the factors, with or without association with copper metabolism, underlying the neurological presentation for which treatment needs to be targeted to improve the clinical outcome of this subgroup.

scholarly journals Histopathology of Wilson Disease

2020 ◽  
Author(s):  
Nese Karadag Soylu
Keyword(s):  
Wilson Disease ◽  
Psychiatric Symptoms ◽  
Copper Metabolism ◽  
Copper Accumulation ◽  
Serum Ceruloplasmin ◽  
Liver Histopathology ◽  
Urinary Copper ◽  
Clinical Presentations ◽  
P Type ◽  
Age Range

Wilson Disease (WD) is a genetic metabolic disease of copper metabolism. The implicated gene is ATP7B, encodes a P-type ATPase which transports copper. The resultant defective metabolism of copper results in copper accumulation in multiple tissues especially liver, eye and central nervous system. WD occurs worldwide, usually between 5 and 35 years; a wider age range is also reported. Clinical presentations are diverse and include combinations of hepatic, neurological, ophthalmic and psychiatric manifestations. Other organs or tissues may also be affected. Biochemical abnormalities such as serum ceruloplasmin and 24-h urinary copper excretion are important for the diagnosis but are not always abnormal in WD. The liver histopathology has several different patterns from mild nonspecific changes to acute fulminant hepatitis and cirrhosis. Copper histochemistry is helpful in diagnosis. Genetic testing is another diagnostic tool. It is important to diagnose WD because it is fatal when overlooked, curable when diagnosed. The diagnosis should be keep in mind at all ages in patients with hepatic disease, neurological disease, or psychiatric symptoms.

Germ cell tumors in the basal ganglia: problems of early diagnosis and treatment

2008 ◽  
Vol 2 (2) ◽  
pp. 118-124 ◽  
Author(s):  
Yukihiko Sonoda ◽  
Toshihiro Kumabe ◽  
Shin-Ichiro Sugiyama ◽  
Masayuki Kanamori ◽  
Yoji Yamashita ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Early Diagnosis ◽  
Germ Cell ◽  
Precocious Puberty ◽  
Germ Cell Tumors ◽  
Young Patients ◽  
Early Recurrence ◽  
Initial Therapy ◽  
Motor Weakness ◽  
Delay In Diagnosis

Object Intracranial germ cell tumors (GCTs) originating in the basal ganglia are rare. The authors investigated factors related to the diagnosis of these lesions as well as outcome in order to help decrease the time to diagnosis and improve treatment efficacy. Methods The authors reviewed the clinical features of 142 cases of intracranial GCT in their institute. Fourteen cases of basal ganglia GCT were identified. The symptoms, neuroimaging findings, delay between symptom onset and diagnosis or treatment, initial and further treatment, and outcome were investigated. Results Major symptoms were motor weakness and precocious puberty. Gadolinium-enhanced T1-weighted MR images showed enhancement in 8 of 11 patients examined, but only slight hyperintensity without enhancement in 2 patients. Ipsilateral peduncle and hemispheric atrophy were found in 3 and 4 patients, respectively. Cases of basal ganglia GCT were characterized by a longer delay from the initial neuroimaging examination to diagnosis compared with GCT in other regions. Five patients had aggravated hemiparesis in the extremities due to the delay in diagnosis. Despite good response to the initial therapy, 5 patients experienced recurrence; 2 of these 5 had malignant GCTs, and 3 had been treated only with chemotherapy or radiochemotherapy with insufficient radiation dose and field. Finally, the 2 patients with malignant GCTs died of the disease, and 1 died of aspiration pneumonia due to dissemination around the brainstem. Conclusions Early diagnosis requires MR imaging with administration of contrast medium in young patients presenting with motor weakness and/or precocious puberty. Serial neuroimaging studies should be performed if any tiny lesion is detected in the basal ganglia. Since insufficient treatment resulted in early recurrence, radiation therapy with adequate dose and field is essential.

Copper-Induced Epigenetic Changes Shape the Clinical Phenotype in Wilson Disease

2020 ◽  
Vol 27 ◽  
Author(s):  
Daniela Fanni ◽  
Clara Gerosa ◽  
Valeria Marina Nurchi ◽  
Rosita Cappai ◽  
Marta Mureddu ◽  
...  
Keyword(s):  
Wilson Disease ◽  
Clinical Presentation ◽  
Clinical Phenotype ◽  
Methylation Status ◽  
Copper Metabolism ◽  
Epigenetic Factors ◽  
Genetic Changes ◽  
Illness Onset ◽  
Phenotypic Manifestation ◽  
Copper Overload

: Wilson disease is a congenital disorder of copper metabolism whose pathogenesis remains, al least in part, unknown. Subjects carrying the same genotype may show completely different phenotypes, differing for the age at illness onset or for the hepatic, neurologic or psychiatric clinical presentation. The inhability to find a unequivocal correlation between the type of mutation in the ATPase copper transporting beta (ATP7B) gene and the phenotypic manifestation, induced many authors to look for epigenetic factors interacting with the genetic changes. Here the evidences regarding the ability of copper overload to change the global DNA methylation status are discussed.

scholarly journals Investigation of the Wilson gene ATP7B transcriptional start site and the effect of core promoter alterations

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Clemens Höflich ◽  
Angela Brieger ◽  
Stefan Zeuzem ◽  
Guido Plotz
Keyword(s):  
Wilson Disease ◽  
Transcription Initiation ◽  
Transcriptional Activity ◽  
Core Promoter ◽  
Transcriptional Start Site ◽  
Copper Metabolism ◽  
Biologically Relevant ◽  
The Core ◽  
Translational Start

AbstractPathogenic genetic variants in the ATP7B gene cause Wilson disease, a recessive disorder of copper metabolism showing a significant variability in clinical phenotype. Promoter mutations have been rarely reported, and controversial data exist on the site of transcription initiation (the core promoter). We quantitatively investigated transcription initiation and found it to be located in immediate proximity of the translational start. The effects human single-nucleotide alterations of conserved bases in the core promoter on transcriptional activity were moderate, explaining why clearly pathogenic mutations within the core promoter have not been reported. Furthermore, the core promoter contains two frequent polymorphisms (rs148013251 and rs2277448) that could contribute to phenotypical variability in Wilson disease patients with incompletely inactivating mutations. However, neither polymorphism significantly modulated ATP7B expression in vitro, nor were copper household parameters in healthy probands affected. In summary, the investigations allowed to determine the biologically relevant site of ATP7B transcription initiation and demonstrated that genetic variations in this site, although being the focus of transcriptional activity, do not contribute significantly to Wilson disease pathogenesis.

scholarly journals Wilson Disease-Induced Acute Liver Failure (NWI = 13) Salvaged without Liver Transplant by Plasmapheresis

2021 ◽  
Vol 11 (01) ◽  
pp. e145-e147
Author(s):  
Nida Mirza ◽  
Ravi Bharadwaj ◽  
Smita Malhotra ◽  
Anupam Sibal
Keyword(s):  
Liver Transplantation ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Wilson Disease ◽  
Prognostic Score ◽  
Prognostic Index ◽  
Kidney Injury ◽  
Copper Metabolism ◽  
Life Saving ◽  
The Brain

AbstractWilson disease (WD) is a disorder of copper metabolism resulting in accumulation of copper in vital organs of the human body, predominantly in the liver and the brain. Acute liver failure in WD has a bad prognosis, especially with a score ≥11 in the revised WD prognostic index; emergency liver transplantation is considered the only life-saving option in this scenario. Here, we reported a girl patient with WD-induced liver failure and poor prognostic score who was rescued by plasmapheresis. She also manifested severe Coombs negative hemolytic anemia and acute kidney injury. This case report highlights the utility of an adjunctive modality besides liver transplantation for the management of fulminant liver failure caused by WD.

Wilson Disease

1996 ◽  
Vol 17 (12) ◽  
pp. 448-448
Author(s):  
Philip O. Ozuah
Keyword(s):  
Biliary Excretion ◽  
Wilson Disease ◽  
Autosomal Recessive ◽  
Copper Metabolism ◽  
The Body ◽  
Hepatolenticular Degeneration ◽  
Dietary Copper ◽  
Hepatic Copper ◽  
Excess Copper ◽  
Excessive Accumulation

Wilson disease (hepatolenticular degeneration) is an autosomal recessive, inherited disorder of copper metabolism resulting in excessive accumulation of copper in the liver, brain, and other organs of the body. The manifestations of the disease are related directly to this accumulation of copper. Copper homeostasis normally is a product of the balance between intestinal absorption of dietary copper and hepatic biliary excretion of excess copper. In Wilson disease, incorporation of hepatic copper into ceruloplasmin is defective and excretion of copper in the bile is reduced. A low level of ceruloplasmin, which until a few years ago was erroneously considered to be the basis for the disease, is a consequence of the underlying metabolic defect.

scholarly journals A Case Report and Literature Review of Wilson Disease

2020 ◽  
Vol 4 (3) ◽  
Author(s):  
Panpan Chen ◽  
Yingying Zhang ◽  
Linqing Qiu ◽  
Xinxin Yu
Keyword(s):  
Wilson Disease ◽  
Clinical Characteristics ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Hereditary Disease ◽  
Abnormal Liver Function ◽  
Atp7b Gene ◽  
Literature Reference ◽  
Urinary Copper

To investigate the clinical characteristics, auxiliary examination and treatment of Wilson’s disease(WD). The clinical data of a child with WD were summarized and analyzed comprehensively in conjunction with the literature reference. WD is a hereditary disease with a large age span, diverse early symptoms, high misdiagnosis rate, abnormal liver function, decreased ceruloplasmin, increased urinary copper, K-F rings, ATP7B gene mutation, ATP7B gene mutations, and abnormalities in abdominal and cranial brain imaging, which can be clearly diagnosed and require lifelong treatment. WD can be diagnosed according to the clinical manifestations and auxiliary examination to reduce misdiagnosis. The timely diagnosis and treatment will improve the prognosis the quality of life.

scholarly journals Immunoglobulin A Nephropathy as the First Clinical Presentation of Wilson Disease: A Case Report and Literature Review

2021 ◽  
Author(s):  
Yong-Zhe Zhang ◽  
Geng Jian ◽  
Ping He ◽  
Rui Yu ◽  
Mi Tian ◽  
...  
Keyword(s):  
Renal Function ◽  
Iga Nephropathy ◽  
Wilson Disease ◽  
Genetic Disorder ◽  
Immunoglobulin A ◽  
Elevated Serum ◽  
Clinical Manifestations ◽  
Kidney Injury ◽  
Copper Metabolism ◽  
Normal Liver

Abstract Background: Wilson disease (WD) is a rare genetic disorder of copper metabolism. The difference in copper tissue accumulation lead to various clinical manifestations, including some atypical presentations. The complex clinical picture makes it easy to miss and misdiagnose, even delay the best chance for treatment. Case presentation: A 26-year-old male patient who had nephritis-range proteinuria and elevated serum creatinine. The renal pathology indicated Immunoglobulin A (IgA) nephropathy and tubular injury which was inconsistent with glomerular lesions. Cirrhosis was also detected by imaging examination. Considering both kidney injury and liver damage, WD was suspected. According to further detected results of abnormal copper metabolism, corneal Kayser-Fleischer rings(K-F rings), and genetic disorder of ATP7B gene, he was finally diagnosed as a case of WD.The patient was given oral penicillamine and zinc sulfate daily and he was also prescribed losartan to control proteinuria on the premise of monitoring renal function and blood pressure. During the 2 years follow-up, the patient’s 24h uric cooper dropped to normal. The sign of tremor hands disappeared. The Urine protein and renal function keep stable. The patient had normal liver function and maintained good quality of daily life. Conclusions: In some cases, IgA nephropathy patients with suspicious and unexplained neurological and liver symptoms cannot be ignored. They may eventually be diagnosed with WD.

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