Genetic Disorder Of Copper Metabolism Research Articles

Metallothionein: a game changer in histopathological diagnosis of Wilson disease.

Wilson disease (WD) is a genetic disorder of copper metabolism caused by mutations in the ATP7B gene. Toxic copper accumulation leads to hepatic, neurologic, and psychiatric disorders with variable presentation. Metallothionein (MT) immunohistochemistry was proposed as a diagnostic marker. MT immunohistochemistry was performed on liver specimens of WD patients (n = 64) and control cases (n = 160) including acute liver failure, steatotic liver disease, autoimmune hepatitis, normal liver, primary biliary cholangitis, primary and secondary sclerosing cholangitis, and progressive familial intrahepatic cholestasis. The optimal cutoff for detection of WD was determined by receiver operating characteristic (ROC) analysis. At least moderate staining in >50% of hepatocytes was observed in 81% of analysed liver specimens (n = 56/69) of WD patients, while only five control cases showed this staining pattern. The sensitivity, specificity, and accuracy for a new diagnosis of WD were 85.7%, 96.9%, and 94.9%, respectively. Sensitivity in nonfibrotic patients was 70.6% and this MT pattern was robust in small biopsies. Thehepatic copper concentration was similar between MT-positive and MT-negative liver samples (P > 0.05). Zinc treatment may induce hepatocellular MT expression. Kayser-Fleischer rings (50% versus 15%) and neurologic disorders (50% versus 13%) were significantly more prevalent in MT-negative compared to MT-positive WD patients, respectively. MT immunostaining is an excellent biomarker for histological diagnosis of WD, should be incorporated in the diagnostic work-up of patients with potential WD, and is useful in a modified Leipzig score.

“Because it is a rare disease…it needs to be brought to attention that there are things out of the norm”: a qualitative study of patient and physician experiences of Wilson disease diagnosis and management in the US

BackgroundWilson disease (WD) is a genetic disorder of copper metabolism that leads to copper accumulation in various organs, primarily the liver and brain, resulting in heterogenous hepatic, neurologic, and psychiatric symptoms. Diagnosis can occur at any age, requiring lifelong treatment, which can involve liver transplantation. This qualitative study aims to understand the wider patient and physician experience of the diagnosis and management of WD in the US.MethodsPrimary data were collected from 1:1 semi structured interviews with US-based patients and physicians and thematically analyzed with NVivo.ResultsTwelve WD patients and 7 specialist WD physicians (hepatologists and neurologists) were interviewed. Analysis of the interviews revealed 18 themes, which were organized into 5 overarching categories: (1) Diagnosis journey, (2) Multidisciplinary approach, (3) Medication, (4) The role of insurance, and (5) Education, awareness, and support. Patients who presented with psychiatric or neurological symptoms reported longer diagnostic journeys (range 1 to 16 years) than those presenting with hepatic symptoms or through genetic screening (range 2 weeks to 3 years). All were also affected by geographical proximity to WD specialists and access to comprehensive insurance. Exploratory testing was often burdensome for patients, but receipt of a definitive diagnosis led to relief for some. Physicians emphasized the importance of multidisciplinary teams beyond hepatology, neurology, and psychiatry and recommended a combination of chelation, zinc, and a low-copper diet; however, only half the patients in this sample were on a chelator, and some struggled to access prescription zinc due to insurance issues. Caregivers often advocated for and supported adolescents with their medication and dietary regimen. Patients and physicians recommended more education and awareness for the healthcare community.ConclusionsWD requires the coordination of care and medication among several specialists due to its complex nature, but many patients do not have access to multiple specialties due to geographical or insurance barriers. Because some patients cannot be treated in Centers of Excellence, easy access to reliable and up-to-date information is important to empower physicians, patients, and their caregivers in managing the condition, along with general community outreach programs.

Clinical Characteristics, Genetic Features, and Long-Term Outcome of Wilson's Disease in a Taiwanese Population: An 11-Year Follow-Up Study.

ObjectiveaaWilson's disease (WD) is a rare genetic disorder of copper metabolism, and longitudinal follow-up studies are limited. We performed a retrospective analysis to determine the clinical characteristics and long-term outcomes in a large WD cohort. MethodsaaMedical records of WD patients diagnosed from 2006-2021 at National Taiwan University Hospital were retrospectively evaluated for clinical presentations, neuroimages, genetic information, and follow-up outcomes. ResultsaaThe present study enrolled 123 WD patients (mean follow-up: 11.12 ± 7.41 years), including 74 patients (60.2%) with hepatic features and 49 patients (39.8%) with predominantly neuropsychiatric symptoms. Compared to the hepatic group, the neuropsychiatric group exhibited more Kayser-Fleischer rings (77.6% vs. 41.9%, p < 0.01), lower serum ceruloplasmin levels (4.9 ± 3.9 vs. 6.3 ± 3.9 mg/dL, p < 0.01), smaller total brain and subcortical gray matter volumes (p < 0.0001), and worse functional outcomes during follow-up (p = 0.0003). Among patients with available DNA samples (n = 59), the most common mutations were p.R778L (allelic frequency of 22.03%) followed by p.P992L (11.86%) and p.T935M (9.32%). Patients with at least one allele of p.R778L had a younger onset age (p = 0.04), lower ceruloplasmin levels (p < 0.01), lower serum copper levels (p = 0.03), higher percentage of the hepatic form (p = 0.03), and a better functional outcome during follow-up (p = 0.0012) compared to patients with other genetic variations. ConclusionaaThe distinct clinical characteristics and long-term outcomes of patients in our cohort support the ethnic differences regarding the mutational spectrum and clinical presentations in WD.

Wilson’s disease - a current approach to diagnostics and treatment. A literature review

Introduction and purpose Wilson’s disease is a rare autosomal recessive genetic disorder of copper metabolism. Its global genetic prevalence is estimated at around 1:30 000. However, in the case of many patients, it takes a long time to make a diagnosis, which delays introducing the right treatment.  This review aims to gather current knowledge about clinical manifestations, diagnosis, and treatment of Wilson’s disease. Material and methods This review was based on available data collected in the PubMed database, using the following keywords:  „Wilson’s disease”, „Wilson’s disease treatment”, „Wilson’s disease Pathogenesis”, and “Wilson’s disease Diagnosis”. ConclusionsThe diagnosis of Wilson’s disease is often delayed due to the wide spectrum of clinical manifestations. Screening of family members of people affected with Wilson’s disease can speed up the diagnosis in yet asymptomatic patients.Raising awareness about Wilson’s disease and diagnosing patients before the onset of serious symptoms may bring earlier diagnosis and improvement in the patient’s quality of life.

An Update on the Future of Wilson Disease Management.

The recognition of Wilson disease (WD) has progressed over the last century from a neurologic disorder associated with liver disease to the understanding that WD is a rare autosomal recessive genetic disorder of copper metabolism. Due to WD's myriad manifestations, its rarity, and its broad range of symptoms, differential diagnosis may be challenging, leading to delays in treatment initiation. This Neuroscience Commentary reviews diagnostic acumen and the latest updates in the field, including key clinical data and novel therapies in late-stage development, all of which ensure optimal management of WD in the coming years.

Pearls & Oy-sters: Challenges and Controversies in Wilson Disease.

Wilson disease (WD) is a genetic disorder of copper metabolism caused by variants in the ATP7B gene, which are inherited in an autosomal recessive pattern. Despite all the advances made on pathogenesis, cellular biology, and genetics, to date, WD remains a diagnostic and therapeutic challenge. With this series of cases, we aim to illustrate the main challenges that clinicians may encounter when dealing with patients with WD: the difficulties with clinical diagnosis, the therapeutic management of WD and the indication for advanced therapies, management during pregnancy, and genotype-phenotype correlations.

Liver transplantation as a treatment for Wilson\u2019s disease with neurological presentation: a systematic literature review

IntroductionWilson’s disease (WD) is a potentially treatable, genetic disorder of copper metabolism, with survival similar to healthy populations if controlled. However, in almost 50% of WD patients, neurological symptoms persist despite treatment, and in up to 10% of patients, neurological deterioration is irreversible. International guidelines on WD treatment do not recommend liver transplantation (LT) as a treatment for neurological symptoms in WD. However, such treatment has been assessed in retrospective analyses, case and series reports. We aimed to systematically assess all available evidence on the effectiveness and safety of LT in WD patients with neurological presentation.MethodsThis systematic literature review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were identified by searching the PubMed database (up to 6 April 2021) and by screening reference lists.ResultsBased on the systematic literature review, 48 articles were identified, showing outcomes of LT in 302 WD patients with neurological symptoms. Of these patients, major improvement was found in 215 cases (71.2%), with no difference in neurological status before and after LT in 21 cases (6.9%). There were 29 deaths (9.6%), neurological worsening in 24 cases (7.9%), and 13 cases (4.3%) were lost to follow-up.ConclusionsThe results suggest that LT is a promising method of WD management in patients with severe, neurological symptoms, particularly if the patient has not responded to pharmacological de-coppering treatment. Further studies of LT in these patients are warranted.

Immunoglobulin a nephropathy as the first clinical presentation of Wilson disease: a case report and literature review

BackgroundWilson disease (WD) is a rare genetic disorder of copper metabolism. Differences in copper tissue accumulation lead to various clinical manifestations, including some atypical presentations. The complex clinical features of WD make diagnosis challenging, delaying the best chance for treatment.Case presentationWe report a case of a 26-year-old man with 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. Based on results showing abnormal copper metabolism, corneal Kayser–Fleischer rings, and genetic disorders in the ATP7B gene, the patient was finally diagnosed with WD. After treatment with oral penicillamine, zinc sulfate and losartan, the patient showed alleviation of both WD and nephropathy after 3 years of follow-up. He maintained a good quality of daily life.ConclusionThis case highlights that unexplained neurological and liver symptoms in patients with IgA nephropathy can be clues for WD.

Outcome of low dose D-penicillamine therapy of neurologic wilson disease- a longitudinal observational study

Background: Wilson disease is genetic disorder of copper metabolism which causes hepatic & neurologic manifestations mainly. Chelation therapy specially penicillamine is given as first line treatment in children with symptomatic wilson disease. Objective: To assess the safety & the clinical outcome of treatment with low dose penicillamine in Neurologic wilson disease

Estimating the clinical prevalence of Wilson’s disease in the UK

Background & AimsThe clinical prevalence of Wilson’s disease (WD) in the UK remains unknown. The estimated genetic prevalence in the UK, 142/million, is higher than the clinical prevalence (15/million) reported in other European studies. The aim of this study was to estimate the clinical prevalence of WD utilising readily available laboratory and clinical data.MethodPatients with WD who attended Nottingham University Hospital NHS Trust (NUH) between 2011 and 2018 were identified using multiple sources of case ascertainment: serum ceruloplasmin, 24-hour urinary copper, ‘Wilson’ in liver biopsy report, hospital prescription for penicillamine/trientine/zinc and admission coded with ICD-10 Code E83.0 (disorder of copper metabolism). Potential cases were identified using the Leipzig score, diagnosis was confirmed in hospital records and the point prevalence was calculated using the Office for National Statistics mid-2017 population estimates.ResultsA total of 1,794 patients were identified from ≥1 source; 19 patients had WD, of whom 11 were from within the study catchment area and alive at the time of point prevalence estimation. Twenty-nine patients had a Leipzig score ≥2 without a diagnosis of WD, but none had WD on screening (n = 16). The overall prevalence of WD was 15.5/million; males 16.9/million and females 14.1/million.ConclusionThis is the first UK population-based study to assess the clinical prevalence of WD. The reported clinical prevalence is lower than the UK genetic prevalence, but comparable to the clinical prevalence reported in Europe. The case ascertainment approach used in this study may be cost-effective, and similar practises could be adopted nationally.Lay summaryOur study estimates the clinical prevalence of Wilson’s disease, a rare genetic disorder of copper metabolism, in the UK. The estimated clinical prevalence is this study is markedly lower than the estimated UK genetic prevalence.

Neurological features and outcomes of Wilson's disease: a single-center experience.

Wilson's disease (WD) is an autosomal recessive genetic disorder of copper metabolism, and WD patients can present with neurologic symptoms. We aimed to report the general characteristics and prognosis of a Turkish series of WD patients with neurological manifestations. A total of 12,352 patients were screened from the patient database, and 53 WD patients were included. Patients were classified based on the predominant neurological syndrome type including tremor, dystonia, parkinsonism, or discrete neurological signs and were classified as having "good outcome," "stable," and "poor outcome" according to their treatment response. There were 32 male and 21 female patients, aged 20-66 years. The mean follow-up was 11.3 ± 4.56 years. Sixty-two percent of patients presented predominantly with neurological symptoms. Neurological WD diagnosis was established after a mean time delay of 2.3 years from the WD diagnosis. The most common neurological manifestation was dystonia, followed by tremor and parkinsonism. Fifteen patients had a family history of WD. Consanguinity was present in 20 patients. Patients were treated with D-penicillamine, trientine, zinc salts, or their combinations. Besides the main treatments, 41 patients were on symptomatic treatment for neurologic symptoms. Thirty-six patients had a "good outcome," five patients were stable, and six patients had "poor outcome." Post-chelation neurological worsening was observed in 11 patients. WD should be considered in differential diagnosis in any patient with unexplained neurologic symptoms. Early diagnosis is important, and appropriate treatment should be promptly initiated to prevent progressive and irreversible damage, with good prognosis and stable disease in the majority of the patients with treatment compliance.

ATP7B variant penetrance explains differences between genetic and clinical prevalence estimates for Wilson disease.

Wilson disease (WD) is a genetic disorder of copper metabolism caused by variants in the copper transporting P-type ATPase gene ATP7B. Estimates for WD population prevalence vary with 1 in 30,000 generally quoted. However, some genetic studies have reported much higher prevalence rates. The aim of this study was to estimate the population prevalence of WD and the pathogenicity/penetrance of WD variants by determining the frequency of ATP7B variants in a genomic sequence database. A catalogue of WD-associated ATP7B variants was constructed, and then, frequency information for these was extracted from the gnomAD data set. Pathogenicity of variants was assessed by (a) comparing gnomAD allele frequencies against the number of reports for variants in the WD literature and (b) using variant effect prediction algorithms. 231 WD-associated ATP7B variants were identified in the gnomAD data set, giving an initial estimated population prevalence of around 1 in 2400. After exclusion of WD-associated ATP7B variants with predicted low penetrance, the revised estimate showed a prevalence of around 1 in 20,000, with higher rates in the Asian and Ashkenazi Jewish populations. Reanalysis of other recent genetic studies using our penetrance criteria also predicted lower population prevalences for WD in the UK and France than had been reported. Our results suggest that differences in variant penetrance can explain the discrepancy between reported epidemiological and genetic prevalences of WD. They also highlight the challenge in defining penetrance when assigning causality to some ATP7B variants.

Wilson disease: 30-year data on epidemiology, clinical presentation, treatment modalities and disease outcomes from two tertiary Greek centers

Wilson disease is a rare genetic disorder of copper metabolism with a wide range of clinical presentations. The aim of this study is to describe the 30-year clinical experience in the management of Wilson disease patients followed at two Greek referral centers. A retrospective chart review was performed to identify past and present Wilson disease patients diagnosed during the last 30 years. Sixty-three patients were included. The median age of diagnosis was 19 (3-59) years, while nine (14%) patients were older than 40 years old. Clinical presentation included asymptomatic liver disease (57.1%), neurological disease (20.6%), overt liver disease (12.7%), acute liver failure (6.3%) and other (3.2%). Kayser-Fleischer rings were detected in 27/62 with a higher frequency in neurologic patients (P < 0.001). Ceruloplasmin values were low in 55/63 with significantly lower values in patients with neurological disease (P = 0.048) and in cirrhotic patients (P = 0.017). Increased 24-hour urine copper was measured in 59/63 patients. D-penicillamine was administered in 56/63 patients (88.8%), followed by trientine (6/63, 9.5%), while one patient needed liver transplantation at baseline. At least one treatment switch was performed in 18 patients. By the end of follow-up, all non-cirrhotic patients (25/25) were stable, 3/23 (13%) cirrhotic developed decompensated liver disease, two developed HCC, three received a liver transplant and two died. Five out of 13 neurologic patients had persisting symptoms despite treatment. Wilson disease presents with a wide spectrum of clinical manifestations and should be investigated even in older patients, as early diagnosis, close follow-up and treatment monitoring usually provide favorable outcomes.

Menkes disease – a multidisciplinary approach for a proper evolution

  Menkes disease is a genetic disorder of copper metabolism that is detectable before birth. It is characterized by seizures, mental retardation, stunted growth, failure to thrive, unstable body temperature, and very unusual color and texture of hair.The incidence of Menkes disease is about 1: 300.000 newborns in Europe, mainly involving boys.&#x0D;   In this case, we present a 3 year old boy, known with Menkes disease from 4 months old, who was admitted to hospital for recurrent acute upper respiratory tract infections (URI). In 2016 he was hospitalized for craniofacial dysmorphism and marked generalized hypotonia, after a paroxysmal cerebral event with loss of consciousness, capping eyes and generalized hypotonia, lasting about 1 hour, at home. Except for these, clinical examination showed deformed thorax, prominent sternum with wide bases, deformed lower legs. Dermatologic and neurologic examination showed the typical aspect of kinky hair and specific epileptic-wave elements on EEG. Based on all these, but also low levels of copper and ceruloplamin, the patient was diagnosed with Menkes disease. He is treated with Phenobarbital (40 mg/day), Valproic acid (1.5 mg x3/day), Diazepam for convulsions and Metamizole (300 mg). The evolution was favorable, without seizures, but with numerous respiratory infections, treated with antibiotics.&#x0D;   In conclusion, this case is distinguished by the fact that Menkes disease, an extremely rare condition, can manifest initially by repeated respiratory infections that require a multidisciplinary approach for an early diagnosis, so the patients could surpass the age of three years, noted in literature as the maximum age of survival.

Targeting Higher Levels of Tau Protein in Ukrainian Patients with Wilson's Disease.

IntroductionWilson’s disease (WD) is a rare genetic disorder of copper metabolism in which impaired copper homeostasis may enhance amyloid aggregation and trigger neurodegeneration. Tau protein is a highly soluble microtubule-associated phosphoprotein that plays a significant role in microtubule stabilization; it is also a critical component of neurotoxic degenerative mechanisms. Tau has been shown to be involved in neuronal degeneration and axonal damage, and impaired copper metabolism has been shown to be involved in copper intoxication and thus associated with the processes of neurodegeneration and cellular damage. We have therefore investigated tau protein as a potential marker of axonal impairment and neurodegeneration.MethodsPatients with WD (n = 47; mean age ± standard deviation [SD] 30.19 ± 7.87 years; mean disease duration : 10.06 ± 3.9 years) and healthy controls (HC; n = 30; mean age 29.6 ± 4.73 years) were tested for serum tau protein levels using an enzyme-linked immunosorbent assay method. All patients were receiving a stable penicillamine dose as ongoing therapy.ResultsPatients with WD had a higher mean tau protein level than did the HC (221.7 ± 135.1 vs. 71.14 ± 20.56 pg/mL, p < 0.0001). Patients with WD also had abnormally high serum tau protein levels (t statistic 6.047, 95% confidence interval − 218.2 to − 95.86) in both the cerebral and hepatocerebral forms of WD, with patients having the cerebral form showing a tendency toward higher tau levels. We found that tau protein did not differ according to gender, disease duration, age at disease onset, ceruloplasmin serum level and copper serum level.ConclusionThis study provides novel data revealing that high tau protein levels in WD patients could be a potential biomarker for axonal impairment and possible neuronal damage due to tau protein, leading to neurodegeneration in WD.

Microstructure changes in whiter matter relate to cognitive impairment in Wilson's disease.

Purpose: Wilson’s disease (WD) is a genetic disorder of copper metabolism with pathological copper accumulation in the brain. The purpose of the present study was to evaluate the relationship between the damaged white matter and the impaired cognitive function in WD patients. Materials and methods: Thirty WD adolescents and thirty age- and sex-matched healthy controls (HC) were enrolled. All subjects had received brain MRI, including conventional and diffusion-tensor imaging (DTI) scans. The DTI parameter of fractional anisotropy (FA) was calculated by diffusion kurtosis estimator software. The t test was used to compare the differences between two groups. The correlation between cognitive function and whiter matter disorders were analyzed by linear regression. The results of FA parameter and MD parameter intergroup analysis were both corrected with False Discovery Rate (FDR) simulations by SPSS. Results: WD adolescents showed significantly lower scores of time-based prospective memory (TBPM) and verbal fluency test (VFT) compared with HC. We found significantly higher FA in the right thalamus, right lentiform nucleus, left thalamus, left lentiform nucleus, and brain stem in WD adolescents. Besides, WD adolescents exhibited significantly lower FA in right cerebellum and cingulum and left middle frontal lobe compared with controls (P<0.05). There were significantly negative correlations between FA in bilateral lentiform and thalamus and cognitive impairment in WD adolescents (P<0.05). Conclusion: The whiter matter of WD adolescents was impaired and mainly distributed in subcortical brain regions. The impaired cognitive function was affected by the damaged whiter matter. The present study may be helpful for recognition and understanding of WD.

Assessment of LV Function in Children with Wilson’s Disease: Speckle Tracking Imaging Study

Background and Objective: Wilson’s disease is a genetic disorder of copper metabolism that affects liver and other organs including heart. In early stages of myocardial affection, the left ventricle (LV) appears apparently normal when evaluated by traditional two-dimensional (2D) echocardiography. The aim of this study was to detect subclinical LV dysfunction in children with Wilson’s disease using 2D speckle tracking echocardiography. Patients and Methods: Twenty children with Wilson’s disease were compared with age- and sex-matched 20 healthy children. All subjects were evaluated by traditional 2D echocardiography and speckle tracking echocardiography. Results: There were no significant differences between patients and controls regarding conventional echo parameters except for lower E mitral flow and E' annular septal peak velocity in patient group. The regional peak longitudinal strain of apical 4 chamber view was -17.8% ± 4.2% in patients and -20.1% ± 2.3 % in control subjects (P = 0.043), and for apical 2 chambers view, it was -20.1%± 3.6% in patients and -22.6% ± 3.4% in control subjects (P = 0.034) and it was -18% ± 3.5% in patients and -20.5% ± 3.2% in control subjects (P = 0.025) in apical long axis view. The global peak longitudinal strain was also lower in patients than control group (18.3% ± 3.2%, and 20.85% ± 2.4%) respectively (P = 0.014). There were no significant differences between both groups regarding circumferential and radial strains (P > 0.05). Conclusions: Despite apparently normal LV systolic function, the children with Wilson’s disease demonstrated significantly lower peak longitudinal strain as an indicator for early affection of LV systolic function.

The results of 6 years of physiotherapy and rehabilitation in an adolescent with Neuro-Wilson’s disease

Background: Neuro-Wilson’s disease (NWD) is a rare autosomal recessive genetic disorder of copper metabolism, which is characterized by hepatic and neurological manifestations. The neurological manifestations usually present with movement disorders, tremor, lack of motor coordination, drooling, dysarthria, dystonia, and spasticity.

Incidental Diagnosis of Wilsonʼs Disease: A Case Report

Wilson's disease (WD) is a genetic disorder of copper metabolism caused by complete absence or dysfunction of a copper transporting enzyme which is a transmembrane protein ATPase (ATP7B) encoded on chromosome 13. The incidence of this condition is seen in 1 in 30 000 individuals. The presentation of WD is variable and usually involves the hepatic and neuropsychiatric systems with symptoms ranging from chronic liver disease, compensated or decompensated cirrhosis, fulminant liver failure, dystonia,choreiform movements, tremor, gait disturbances, personality changes and cognitive impairments which are attributed to copper accumulation. We present a case where routine imaging for a persistent problem considered to be chronic pelvic pain led to the diagnosis of WD. A 28-year-old female with history of longstanding depression and Type 1 Diabetes Mellitus was admitted with recurrent abdominopelvic pain. She had been hospitalized multiple times for evaluation of recurrent abdominopelvic pain. Her initial episode of abdominopelvic pain was evaluated with a CT Abdomen that showed a pelvic abscess which was managed surgically with complete resolution and since then, she has had extensive evaluation including serial imaging during subsequent hospitalizations which were negative for any acute process. During this admission, a repeat CT Abdomen showed new onset cirrhosis of the liver which was absent on previous imaging studies. Patient denied alcohol use and after a negative infectious, autoimmune and hematological workup, further laboratory evaluation showed low serum levels of ceruloplasmin (5.4 mg/dl) and an elevated 24 hour urine copper excretion (302 ug/d).Slit light examination of the eyes was negative for Kayser-Fleisher rings. MRI Brain showed T2 high signal intensity in the pons. She was empirically started on zinc gluconate. Genetic testing showed heterozygous mutation in the gene ATP7B and a diagnosis of Wilson's disease was made. Patient continues to be maintained on zinc therapy and is closely being followed as an outpatient for liver transplant evaluation. The diagnosis of WD can be easily missed and if diagnosed early could potentially prevent or reverse many of its serious manifestations. Despite the involvement of the hepatic and neurological system on imaging, our patient was completely asymptomatic which makes this case unique. Our case further reiterates the importance of always keeping WD on the differential in evaluating patients with cirrhosis.

A Child of Wilson’s Disease Presenting with Coprolalia

Wilson’s disease is a rare autosomal recessive genetic disorder of copper metabolism. Neurological and psychiatric manifestations can be a presenting manifestation of Wilson’s disease. We describe a case of a 13 year old child diagnosed with Wilson’s disease who presented with coprolalia (complex vocaltics).