Wilson's Disease (Wilson Disease) is a rare autosomal recessive disorder that results in copper build up in the brain and liver. There are both neuropsychiatric and GI/hepatic signs and symptoms.
Epidemiology
Wilson's disease occurs in about 1 in 30,000 people.
Symptoms usually begin between the ages of 5 and 35 years (average age of 17).
Comorbidity
If detected early and treated appropriately, individuals can have normal health and a normal lifespan.
In untreated cases, the disease is progressive and disease can occur within 5 to 10 years (from severe brain damage, liver failure).
Severe hemolytic anemia can also be an unusual complication of Wilson’s disease.[2]
Symptoms
The clinical spectrum of liver disease can range from being asymptomatic to acute liver failure or cirrhosis
Hepatic/GI symptoms include vomiting, weakness, ascites, edema, jaundice, and jaundice-associated pruritis.
Adults may have additional neuropsychiatric symptoms which can include:
Neurologic symptoms such astremors, muscle stiffness, and aphasia
Psychiatric symptoms (present in about 15% of cases) such as personality changes, anxiety, hallucinations, psychosis, or depressive symptoms.
Pathophysiology
Wilson's disease is an autosomal recessive disorder of copper metabolism in chromosome 13, due to a mutation in the Wilson disease protein (ATP7B) gene.
Copper excretion by the liver is impaired in Wilson's disease
The defective biliary excretion of copper causes copper accumulation in tissues, particularly in the brain (basal ganglia), liver, and cornea[3]
Investigations
In young patients presenting with tremors, one should always order:[4]
Serum ceruloplasmin level (low, due to the shorter half-life of non–copper-bound ceruloplasmin)
Total serum copper (low, since serum ceroplasmin is low)
Free serum copper (elevated)
24-hour urinary copper excretion (universally elevated in untreated individuals)
Ferritin levels (elevated)
Liver biopsy will indicate elevated copper levels due to copper deposition
Genetic testing for ATP7B gene variations can provide diagnostic confirmation if biochemical testing is not definitive
Neuroimaging
CT head will often show signs of atrophic changes in the basal ganglia, cortical, and cerebellar regions that mimics neurodegenerative disease.
MRI head will show increased signal in the basal ganglia and especially in the putamen
Physical Exam
Dysarthric speech is the most common neurological sign[5]
Patients will often appear jaundiced
On gait exam, there is typically an ataxic gait
A “wing-beating” tremor is commonly present as well
Kayser-Fleischer rings, which represent copper deposits in the Descemet membrane of the cornea, are seen on ophthalmoscopic examination by slit lamp.
Kayser-Fleischer rings are a pathognomonic finding of Wilson disease but can be absent in around 50% of patients with Wilson disease.[6]
Patients should be referred to an ophthalmologist for assessment.