Wilson's Disease – Causes, Symptoms & Treatment

What is Wilson's Disease?

Wilson's disease is a rare, autosomal recessive inherited metabolic disorder in which the body is unable to properly excrete copper. This leads to a toxic buildup of copper in the liver, brain, eyes, and other organs. The disease is named after British neurologist Samuel Alexander Kinnier Wilson, who first described it in 1912.

Causes

Wilson's disease is caused by mutations in the ATP7B gene, which encodes a copper-transporting protein in the liver. This protein is normally responsible for excreting excess copper through bile. When both copies of the gene are mutated (autosomal recessive inheritance), this transport mechanism fails and copper accumulates in body tissues.

• Both parents must carry the gene mutation
• Statistically, one in four children of carrier parents will develop the disease
• Approximately 1 in 30,000 people worldwide is affected

Symptoms

Symptoms vary depending on which organs are affected. First signs typically appear between the ages of 5 and 35.

Liver-related symptoms

• Chronic hepatitis (liver inflammation)
• Liver cirrhosis (scarring of the liver)
• Acute liver failure

Neurological and psychiatric symptoms

• Tremor, uncoordinated movements, dysarthria
• Difficulty swallowing and slurred speech
• Personality changes, depression, anxiety disorders
• Psychosis or schizophrenia-like episodes

Eye findings

A characteristic sign of Wilson's disease is the Kayser-Fleischer ring – a golden-brown discoloration at the outer edge of the cornea caused by copper deposits, visible under slit-lamp examination.

Diagnosis

Diagnosing Wilson's disease requires a combination of tests:

• Slit-lamp examination to detect Kayser-Fleischer rings
• Blood tests: measuring ceruloplasmin (usually low) and serum copper levels
• 24-hour urine collection: elevated copper excretion
• Liver biopsy: direct measurement of copper concentration in liver tissue
• Genetic testing for ATP7B mutations

Treatment

Wilson's disease is treatable but not curable. The goal of therapy is to reduce copper levels in the body and prevent organ damage.

Medication

• D-penicillamine: A chelating agent that binds copper and promotes its excretion in urine – considered first-line therapy
• Trientine: An alternative to D-penicillamine for patients who cannot tolerate it
• Zinc salts: Inhibit copper absorption in the gut; suitable for maintenance therapy and asymptomatic patients

Diet

Patients are also advised to avoid copper-rich foods such as organ meats, shellfish, nuts, chocolate, and certain legumes.

Liver transplantation

In cases of severe liver failure or treatment-resistant disease, a liver transplant can be life-saving and corrects the underlying metabolic defect.

Prognosis

With early diagnosis and consistent treatment, most patients can lead a largely normal life. Without treatment, Wilson's disease leads to severe liver and brain damage and can be fatal.

References

1. European Association for the Study of the Liver (EASL): EASL Clinical Practice Guidelines – Wilson's Disease. Journal of Hepatology, 2012.
2. Roberts EA, Schilsky ML: Diagnosis and treatment of Wilson disease – an update. Hepatology, 2008; 47(6): 2089–2111.
3. World Health Organization (WHO): Rare Diseases – Inherited Metabolic Disorders. WHO, Geneva.