11/14/24, 10\:38 AM Wilson’s Disease

Wilson’s Disease

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Wilson's disease\: rare autosomal recessive disorder, 1 in 30,000 prevalence; excess copper in liver, brain.
Cause\: ATP7B gene mutation (chromosome 13); impaired copper transport and bile excretion.
Risk factor\: family history; ATP7B carriers asymptomatic but may have mild copper metabolism issues.
Symptoms\: liver disease, neurological (dystonia, ataxia, tremor), psychiatric (depression, psychosis), Kayser-Fleischer rings.
Investigations\: low serum ceruloplasmin, high 24-hour urinary copper, genetic testing for ATP7B mutations, liver biopsy
(copper >250 mcg/g).
Imaging\: MRI brain (T2 hyperintensity in basal ganglia); supports diagnosis if neurological features.
Management\: penicillamine (
Complications\: liver failure, neuropsychiatric disorders, ascites, variceal bleeding, death if untreated.
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A comprehensive topic overview

Introduction

Wilson's disease is a genetic disorder characterised by abnormal copper metabolism, leading to excessive copper
deposition, primarily in the liver and brain.
¹
The condition typically has a juvenile onset (before 16 years of age), though it can present at any stage of life. It is
considered rare, with a prevalence of approximately 1 in 30,000 individuals.
²

Aetiology

Wilson's disease is an autosomal recessive disorder caused by mutations in the ATP7B gene located on chromosome 13.
3
These mutations impair the function of ATPase, a protein responsible for transporting copper across intracellular
membranes and facilitating its excretion into bile.
The accumulation of excess copper levels increases oxidative stress within cells, leading to clinical manifestations such as
liver injury and neurological de

Risk factors

The primary risk factor for Wilson's disease is inheriting mutations in the ATP7B gene, particularly with a family history of
the condition.
3
Heterozygous carriers of ATP7B mutations are typically asymptomatic but may exhibit mild abnormalities in copper
metabolism.
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Clinical features

History

Wilson's disease can present with a variety of clinical features, including liver disease, progressive neurological disorders,
psychiatric illness, or a combination of these. 4,5
Common symptoms include\:
Dementia
Tremor and dyskinesias
Behavioural changes
Psychosis
Depression
Abdominal pain
Infertility
Acute liver failure
Features of decompensated liver disease (e.g. jaundice, ascites, variceal bleeding or hepatic encephalopathy)
Haemolytic anaemia

Clinical examination

Examination
Ophthalmic
Ophthalmic abnormalities can be observed on slit lamp examination and include\:
Kayser–Fleischer rings\: copper deposits in Descemet's membrane, appearing as rusty-brown rings in the corneas
Sun
Figure 1. Kayser-Fleischer ring
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Figure 2. Sun
Neurological
Neurological features of Wilson's disease may include\:
Ataxia
Dystonic syndrome\: involuntary muscle contractions resulting in abnormal, sometimes painful positions
6
Akinetic-rigid syndrome\: resembling the movements seen in Parkinson's disease
Hepatic
A thorough abdominal examination is crucial when suspecting Wilson's disease. Features of acute or chronic liver failure
may include\:
Ascites
Hepatomegaly/splenomegaly
Oesophageal varices
Jaundice

Di

Wilson's disease is a systemic disease that can mimic other disorders, often leading to delayed diagnosis or misdiagnosis.
It is important to di
Menkes disease\: an X-linked recessive disorder caused by mutations in the ATP7A gene, resulting in a copper
de
7
Aceruloplasminaemia\: characterised by abnormal iron accumulation in the brain and other organs due to mutations in
the ceruloplasmin (CP) gene
8
Liver diseases of di
such as autoimmune hepatitis, alcohol-related liver disease or non-alcoholic fatty liver disease.
2
The presence of personality changes, rigidity, and movement disorders can also often lead to a misdiagnosis of various
Parkinsonian syndromes, as these conditions share similar manifestations.

Investigations

A diagnosis of Wilson's disease is based on clinical history and laboratory investigations.
2, 5

Laboratory investigations

Key laboratory investigations include\:
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Serum ceruloplasmin\: typically low, as it is the primary carrier protein of copper in the blood
Serum copper\: often low, however, serum ‘free' copper (not bound to ceruloplasmin) tends to be elevated
24-hour urinary copper\: re
Genetic testing\: identi

Imaging

MRI brain is useful when neurological symptoms are present. 5
The most common
images involving the basal ganglia and substantia nigra. These
con

Liver biopsy

A liver biopsy is required if the diagnosis remains uncertain. The diagnostic test is a liver biopsy with a quantitative assay of
5
copper.
A hepatic copper concentration greater than 250 micrograms/g is diagnostic for Wilson's disease. However, the absence
of copper staining on liver tissues does not exclude the diagnosis, as copper can be deposited sporadically.
Family screening
Identifying at-risk relatives early is crucial to prevent signi
be o
For two carrier parents, there is a 25% chance of having an a
a carrier. Due to its autosomal recessive inheritance, consanguinity increases the likelihood of carrying the mutated
gene, raising the risk of Wilson's disease.
⁹

Diagnosis

Leipzig criteria

The Leipzig criteria can be used to diagnose Wilson's disease, using several clinical features and investigation
diagnosis is established with a score ≥ 4. A score ≤ 1 indicates that Wilson's disease is unlikely.
10
Table 1. Leipzig criteria
11
The Leipzig criteria

Management

The management of Wilson's disease can be divided into medical and surgical interventions. Scoring systems, such as the
Kings Wilson Index or the Nazer score, help guide treatment decisions.

Medical management

Penicillamine\: the
and may initially worsen neurological symptoms, particularly if the dose is increased too quickly.
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Zinc\: used in addition to penicillamine, as zinc prevents copper absorption and increases its excretion
13
Trientine\: an alternative for patients who cannot tolerate penicillamine

Surgical management

Patients presenting with acute liver failure or decompensated cirrhosis may require a liver transplant.

Information for patients and relatives

Patient education is crucial and should be provided along with guidance for at-risk relatives. This includes advice on
lifestyle changes, such as dietary copper restriction and participation in appropriate family screening programmes.
5, 14
Nazer score
The Nazer Score assesses the severity of liver dysfunction based on levels of aspartate transferase (AST), bilirubin,
and prothrombin time (PT) at admission.
12
Table 2. Nazer Score
The Nazer Score
A Nazer score ≥ 10 indicates severe hepatic failure and suggests the need for liver transplantation. A score of ≤ 9
indicates mild to moderate hepatic failure, which can typically be managed medically in the early stages. However,
liver transplantation may be considered as a second-line option if necessary.

Complications

Patients with Wilson's disease may develop a range of complications, particularly if treatment is delayed. These include\:
2
Liver failure
Hepatic encephalopathy
Splenomegaly
Ascites
Variceal bleeding
Hepatorenal syndrome
Neuropsychiatric manifestations (e.g. cognitive decline, psychiatric disorders)
Death

Prognosis

Untreated Wilson's disease is fatal, primarily due to progressive liver failure or severe neurological damage. Early
recognition and appropriate treatment are essential to prevent mortality from hepatic complications.
With specialist treatment and regular monitoring, patients can signi
Long-term management and lifelong follow-up are necessary to prevent the recurrence of symptoms and to monitor for
complications related to copper accumulation or treatment side e

References

Hedera P. Wilson's disease\: a Master of Disguise. Parkinsonism & Related Disorders. 2019. Available from\: [LINK].
https\://app.geekymedics.com/notebook/2836/ 5/711/14/24, 10\:38 AM Wilson’s Disease
Immergluck J, Anilkumar AC. Wilson Disease. StatPearls Publishing. 2023. Available from\: [LINK].
Schilsky ML, Roberts EA, Bronstein JM, et al. A multidisciplinary approach to the diagnosis and management of Wilson
disease\: Executive summary of the 2022 Practice Guidance on Wilson disease from the American Association for the Study
of Liver Diseases. Hepatology. 2023. Available from\: [LINK].
Shribman S, Marjot T, Sharif A, et al. Investigation and management of Wilson's disease\: a practical guide from the British
Association for the Study of the Liver. The Lancet Gastroenterology & Hepatology. 2022. Available from\: [LINK].
Schilsky ML, To UK. Wilson's disease. BMJ Best Practice. 2023. Available from\: [LINK].
National Organization for Rare Disorders. Dystonia. 2024. Available from\: [LINK].
de Bie P, Muller P, Wijmenga C, et al. Molecular pathogenesis of Wilson and Menkes disease\: correlation of mutations with
molecular defects and disease phenotypes. Journal of Medical Genetics. 2007. Available from\: [LINK].
National Organization for Rare Disorders. Aceruloplasminemia. 2019. Available from\: [LINK].
National Organization for Rare Disorders. Wilson Disease. 2015. Available from\: [LINK].
Kasztelan-Szczerbinska B, Cichoz-Lach H. Wilson's Disease\: An Update on the Diagnostic Workup and Management.
Journal of Clinical Medicine. 2021. Available from\: [LINK].
Ferenci P, Caca K, Loudianos G, et al. Diagnosis and Phenotypic Classi
Available from\: [LINK].
Nazer H, Ede RJ, Mowat AP, et al. Wilson's disease\: Clinical Presentation and Use of Prognostic Index. Gut. 1986. Available
from\: [LINK].
Avan A, Członkowska A, Gaskin S, et al. The Role of Zinc in the Treatment of Wilson's Disease. International Journal of
Molecular Sciences. 2022. Available from\: [LINK].
Poujois A, Woimant F. Wilson's disease\: a 2017 Update. Clinics and Research in Hepatology and Gastroenterology. 2018.
Available from\: [LINK]

Image references

Related notes

Figure 1. Fred HL, van Dijk HA. Kayser-Fleicher ring. License\: [CC BY 3.0].
Figure 2. Imrankabirhossain. SunCC BY-SA 4.0].
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Hyperlipidaemia
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Contents

Introduction
Aetiology
Risk factors
Clinical features
Di
Investigations
Diagnosis
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