Wilson's Disease

>> Hepatolenticular Degeneration

Wilson's Disease is a rare autosomal recessive disorder that results in a copper build up in the brain and liver. There are both neuropsychiatric and GI/hepatic signs and symptoms. Onset is usually in the second or third decade, with dystonia, parkinsonism, or cerebellar ataxia. Patients also may have dysarthria: dysphagia, hypophonia, or seizures. We may detect chronic hepatitis or haemolytic anaemia. Kayser-Fleischer rings comprise brown or green discolouration near the limbus of the cornea and are present in all patients with neurological signs.

Prevalence

Wilson's disease occurs in about 1 in 30,000 people. Symptoms usually begin between the ages of 5 and 35 years. Males and females are equally affected.

Symptoms

Neuropsychiatric Manifestations

Psychiatric symptoms because of Wilson's disease are present in about 15% of patients. It may present with schizophrenia-like changes, depression, or manic-depressive states. Aggressive and self-destructive or antisocial acts may also occur. Intellectual deterioration is mild in the early symptomatic stages (Akil and Brewer, 1995). Tremors, muscle stiffness, aphasia, personality changes, anxiety, and hallucinations. 

Hepatic manifestations

Vomiting, weakness, ascites, oedema, jaundice, and jaundice-associated pruritus.

Neuropathology

Wilson's disease is an autosomal recessive disorder. It is because of a mutation in the Wilson disease protein (ATP7B) gene. It affects the basal ganglia in association with abnormalities in liver function. It results from an autosomal recessive defect in copper metabolism, in a defective P-type adenosine triphosphatase (Cuthbert 1995), which leads to excessive copper deposition in the liver, corneas, and basal ganglia.

Investigations

In patients presenting with tremor should always order:

Serum ceruloplasmin level

24-hour urinary copper excretion

Neuroimaging. 

Physical Examination

Dysarthric speech is the most common neurological sign

Jaundice

On gait exam, ataxic gait

Wing-beating tremor

Kayser-Fleischer rings on ophthalmoscopic examination by slit lamp. Imaging shows the 

Diagnosis

We may establish the diagnosis by slit-lamp examination of the cornea, a serum ceruloplasmin level less than 20 mg/dL, a 24-hour copper excretion of over 100 mg, or a liver biopsy showing increased hepatic copper concentration. Brain imaging will often show signs of neurodegenerative disease. The most specific sign is the face of the giant panda sign—an abnormal signal in the lenticular nuclei, caudate nucleus, thalamus, dentate nuclei, and brain stem. 

Treatment

Treatment of Wilson's disease comprises maintaining a negative copper balance and frequent administration of a copper-chelating agent (Brewer 2005). Patients with advanced disease may require liver transplantation. Neurological symptoms, including dementia, improve with long-term therapy. L-Dopa may be of some benefit in reversing neurological symptoms not improved by direct copper therapies.  

References

1. Litwin, T., Dusek, P., Szafrański, T., Dzieżyc, K., Członkowska, A., & Rybakowski, J. K. (2018). Psychiatric manifestations in Wilson’s disease: possibilities and difficulties for treatment. Therapeutic advances in psychopharmacology, 8(7), 199-211.
2. Dusek, P., Litwin, T., & Członkowska, A. (2019). Neurologic impairment in Wilson disease. Annals of Translational Medicine, 7(Suppl 2).
3. Akil M, Brewer GJ. Psychiatric and behavioural abnormalities in Wilson's disease. Adv Neurol. 1995;65:171-8. PMID: 7872138.
4. Cuthbert JA. Wilson's disease: a new gene and an animal model for an old disease. J Investig Med. 1995;43(4):323-336.