Wilson's Disease

 

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Original Editors - Students from Bellarmine University's Pathophysiology of Complex Patient Problems project.

Top Contributors - Rachel Rawson, Lexi Vessels, Aminat Abolade, Kim Jackson, Vidya Acharya, WikiSysop and Elaine Lonnemann  

Definition/Description

Wilson’s disease, also known as hepatolenticular degeneration, is an autosomal recessive disorder that results from abnormal metabolism of copper. (Wu) It is caused from the mutation of the ATP7B gene, and leads to the accumulation of copper in key organs such as the liver, central nervous system, kidney, cornea and other tissues, resulting in impaired function. (Goodman/Wu) The deposition of copper begins immediately at birth, with symptoms usually presenting in late adolescence. Wilson's disease typically manifests into two common presentations: Liver disease or neurological symptoms due to the liver and the brain being major target organs in the accumulation of copper. Symptomatic adolescents will tend to experience more symptoms related to liver pathologies, while older adults will experience neurological signs and symptoms. (WHJ)

Prevalence

Wilson’s disease is a rare condition, affecting only one person in 30,000 in most populations. (WDA) (Autosomal recessive) The gene frequency for this disease has been found to be 56%, with a carrier frequency of 1 in every 90 people. (WJH) According to recent studies, an increase incidence of this gene mutation has been found in isolated populations like Costa Rica and Sardinia, an island off Italy.

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Characteristics/Clinical Presentation

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Associated Co-morbidities

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Medications

Pharmacological treatment of Wilson’s disease is based around the removal of excess copper from the body, as well preventing the accumulation of it in target organs. (WDA) Chelation therapy drugs, such as Penicillamine and Trientine are used to remove excess copper from the affected organs; they act as binding agents and are removed through urinary excretion. (WDA) Zinc salts are also used to block the intestinal absorption of copper, reducing its accumulation in the body. Zinc salts are shown to be very effective, and is an advantage over other pharmacological agents because of its lack of side effects.

It is recommended that patients who are asymptomatic should receive lower doses of zinc salts or chelators than patients who are symptomatic. Often times, symptomatic patients receive a combination of zinc salts and chelators.

D-Penicillamine:

Initial Dose: 250-500 mg/d with 250 mg increments every 4-7 days in 2-4 divided doses Maintenance Dose: 750-1000 mg/d in 2 doses a day Pediatric Dose: 20mg/kg per day in 2-3 doses daily; maintenance therapy should reduce to 25-30% of dose

Administer drug one hour before or two hours after a meal to avoid inhibition.

Adverse side effects are common and include fever, cutaneous eruptions, neutropenia, lymphadenopathy, and proteinuria

Trientine Dosage:

Initial Dose: 750-1500 mg/d in 2-3 divided doses Maintenance Dose: 750-1000 mg/d in 2-3 divided doses Pediatric Dose: 20mg/kg per day in 2-3 doses daily; maintenance therapy should reduce to 25-30% of dose

Adverse side effects include possible neurotoxicity, dyspepsia, anemia, muscle cramps, and dystonia

Zinc Dosage: Dose: 150 mg/d divided in 3 doses Pediatric dose: 75 mg/d divided in 3 doses

Adverse side effects are minimum and include gastric irritation, alcohol intolerance, headaches, excessive perspiration, and anemia

(WJH)

Compliance with pharmacological intervention poses a significant threat to management of Wilson's disease, especially in patients who are asymptomatic because there is failure to recognize the relationship between medication and the disease progression.

(Handbook)

Diagnostic Tests/Lab Tests/Lab Values

Diagnosis of Wilson’s disease can be confirmed through a multitude of diagnostic tests:

1)Ophthalmalogic slit lamp examination for Kayser-Fleischer rings

2)Serum ceruloplasmin test: >2µg/dL confirms the diagnosis of WD, while <1µg/dL determines a healthy individual.

3)24-hour urine copper test: Levels of copper in urine are increased in WD because there is a decrease in serum binding of copper to ceruloplasmin. Levels in an adult > 100mcg/hr and levels in children > 40mcg/hr confirm WD.

4)Liver biopsy for histology and histochemistry and copper quantification. This is the gold standard for determining the presence of Wilson's disease.(Wu)

5)Genetic testing, haplotype analysis for siblings and mutation analysis

(WDA and WJH)

Due to the heterogeneity of the clinical manifestations, misdiagnosis is common and this leaves patients without timely treatment. (Wu)

Etiology/Causes

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Systemic Involvement

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Medical Management (current best evidence)

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Physical Therapy Management (current best evidence)

Physical therapy can play a major role in the treatment of individuals with Wilson's disease. One of the most common manifestations of this condition is the neurological symptoms that present like a movement disorder. Patients present with dystonia, dyscoordination, tremors and difficulty with balance and walking.

Many patients may face problems if their dystonia worsens and a contracture develops. PT can provide patient education on positioning and stretching to prevent progression of the contracture, in addition to serial casting to reverse an acute contracture.

Physical therapy can be a useful tool in improving balance and coordination through the use of therapeutic activities and exercise, as well as maintaining range of motion.

(WDA, WSD, more?)

While physical therapy plays a crucial role in helping these individuals overcome their neurological symptoms, success with therapy is not possible unless the patient is consistently sticking to their medication regime.

Differential Diagnosis

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Case Reports/ Case Studies

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Resources

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Recent Related Research (from Pubmed)

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References

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