Mixed Hyperkinetic/Hypokinetic Movement Disorders (19, Part 3)

Question 0

What is the pathological mechanism behind Wilson’s disease?

Answer 0

Inability to excrete copper in the biliary system due to mutated ATP7B leads to accumulation of Cu 1st in the liver, then eventually in the brain

Question 1

What is the inheritance pattern of Wilson’s disease? What gene product is mutated?

Answer 1

Autosomal recessive
ATP7B, a copper-transporting ATPase is mutated
*(long arm of chromosome 13)

Question 2

What age range is onset of Wilson’s typically seen in?

Answer 2

Age 10-20 is most common; have been cases as young as 3 and as old as 70

Question 3

Although hepatic symptoms are seen most commonly, what % of patients have neurological symptoms as the initial presenting feature? What is different about age of onset in those presenting with neurological symptoms as first symptoms?

Answer 3

~40% of patients
*patients presenting with neurological symptoms typically have a later age of onset usually closer to 20 (the liver has to fill up before Cu can spill over andk begin depositing in the brain)

Question 4

What is the most common neurological presenting feature of Wilson’s disease?

Answer 4

Tremor - is classically a kinetic, or intention, tremor : only occurs with movement (postural and rest tremors may be present though)

Question 5

What neurological symptom will usually develop eventually in pts with Wilson’s?

Answer 5

Dysarthria (may be extrapyramidal or cerebellar in nature)

*other symptoms include Parkinsonism and chorea

Question 6

What are three psychiatric symptoms that may be seen in Wilson’s, esp in those with neurological symptoms?

Answer 6

1. Personality change
2. Depression/Mania
3. Psychosis
   - also dementia, but this is pretty rare

Question 7

What characteristic finding of Wilson’s disease is virtually always present in patients if neurological or psychiatric dysfunction is present?

Answer 7

Kayser-Fleischer ring

Question 8

Neuronal loss and gliosis are especially prominent in what three parts of the brain in Wilson’s?

Answer 8

1. Putamen
2. Thalamus
3. Cortex

Question 9

What is an Opalski cell and where is it found? (Microscopic hallmark of Wilson’s)

Answer 9

Altered glial cell found in the basal ganglia of affected individuals

Question 10

What 2 serum findings are seen in Wilson’s?

Answer 10

1. Decreased serum ceruloplasmin
2. Increased serum free copper (but serum total copper is decreased, mainly due to decreased ceruloplasmin
   * also increased urinary copper

Question 11

What is the most sensitive and accurate finding for Wilson’s?

Answer 11

Elevation of hepatic copper levels

*genetic testing is impractical due to the huge number of mutations that can cause Wilson’s