21st November 2023

Wilson’s Disease

Although a rare disorder, this seems to be a hot topic for the exam.

Wilson’s disease is a disorder of copper metabolism due to mutations in the ATP7B gene (chromosome 13).

The function of this gene is mainly to move copper across intracellular membranes. This also helps in the production of ceruloplasmin, the copper carrier of the body. The absence of this gene in Wilson’s disease leads to a build up of copper in the liver and low copper in the rest of the body, leading to hepatic injury. Wilson’s disease is sometimes also referred to as hepatolenticular degeneration.

Inheritance – Autosomal recessive.

Ethnic variations – Slavic type shows a late age of onset and neurological features, whereas the juvenile type occurs in Western Europeans and has an age of onset before the age of 16 years. Predominantly hepatic involvement.

Age of onset – Second and third decades. Neuropsychiatric manifestation is common in young adults.

Neuropsychiatric features (commonly asked in the exam)

• Severe depression or various neurotic behavioural patterns.
• Asymmetric tremor – An early neurological sign is seen in nearly half the patients. This can either be a resting, postural or kinetic tremor.
• Dysarthria.
• Ataxia.
• Hypersalivation.
• Mask like facies.
• Pseudobulbar palsy and gait disturbance.

Parkinson’s disease is often a close differential.

Other systemic features

• Hepatic – Acute liver failure, cirrhosis, and fulminant hepatic failure.
• Ocular – Kayser-Fleischer ring – Seen in up to 95% of those with symptomatic disease. A golden-brown ring on the cornea. Although mostly associated with Wilson’s disease, this can also be seen with other hepatic conditions. Sunflower cataracts, optic neuritis and optic disc pallor may be seen.
• Renal – Fanconi’s syndrome may occur with hypercalciuria and nephrocalcinosis.
• Rheumatological – Osteopenia, chondrocalcinosis and chondromalacia patellae.
• Cardiomyopathy.
• Infertility.
• Pancreatitis.

Findings

• KF rings and low serum ceruloplasmin sufficient to make a diagnosis of Wilson’s disease.
• Elevated 24-hour urinary copper excretion.
• Genetic testing is limited.
• Assay by the enzymatic method is accurate.
• Diagnostic test – Liver biopsy.
• MRI scan – Increased density in the basal ganglia – ‘Face of the giant panda’ sign.

References

• Dr Colin Tidy (2014). Wilson’s Disease. Patient.info. Available online at: https://patient.info/doctor/wilsons-disease-pro. [Accessed April 2023]