Wilson's Disease

Question 1

Wilson’s disease: Hepatolenticualr degeneration. Fatal without treatment.

Answer 1

• Copper storage disease
• Kayser-Fleischer rings in eyes.

Question 2

Copper metabolism

Answer 2

• Essential nutrient: many metalloenzymes.
• Intestinal absorption not tightly regulated.
• Regulated at level of excretion (bile)-thus cholestasis can lead to build up of copper.
  -other causes of copper overload: Tyrolean childhood cirrhosis, Indian childhood cirrhosis, idiopathic copper toxicosis

Question 3

Copper Deficiency:

Answer 3

• Menke’s disease: ATP7A.

Question 4

Wilson Disease Gene: ATP7B

Answer 4

-Chromosome 13. Expressed in liver and kidney&raquo_space; lung, placenta and brain.
- ATP7B: P-type copper translocating ATPase found in trans-Golgi. >520 mutations.
- 57% homologous with Menkes protein (ATP7A).
Loss of ATP7B interrupts ceruloplasmin synthesis. also lose ability to secrete copper into the canaliculus. Thus: copper accumulates in hepatocyte and ceruloplasmin levels decrease in the blood.

Question 5

Wilson’s disease Clinical Features

Answer 5

• AR
• Carrier frequency: 1 in 90.
  Clinical presentation
• 1st decade: 75% hepatic
• 2nd decade: 50% liver, 50% neuro-psych.
• 3-4th decade: 75% neuro-psych

Question 6

Copper toxicity symptoms

Answer 6

• Neuropsych: Depression, schizophrenia
• Kayser-Fleischer rings
• Cardiomyopathy
• Liver disease: steatosis,, chronic hepatitis, cirrhosis, fulminant liver failure.
• Hemolysis
• Osteopenia
• Renal disease: Fanconi’s syndrome.

Question 7

Wilsons’ disease liver histology

Answer 7

• acute/chronic hepatitis, fibrosis, cirrhosis, fatty liver.
• periportal glycjogenated nuclei
• hepatic steatosis
• Mallory’s hyaline
• increased pigment (copper/iron)
• Copper stains MAY BE NEGATIVE.
• Lysosomal, released, or regenerative nodules.

Question 8

Diagnosis of Wilson’s disease

Answer 8

3 screening tests: should get all 3.
- serum ceruloplasmin
- 24 hour urine copper collection
- slit lamp exam looking for KF ring.
Confirmation test for Wilson’s
- liver biopsy: >250mcg/g dry weight of copper is cut off for Wilson’s disease
- genetic/molecular testing
Can also use Leipzig Scoring System.

Question 9

Fulminant Wilson Disease

Answer 9

Triad:
- acute liver failure
- non-immune hemolysis (Coombs negative)
- AKI: dialysis
modest elevated of AST and ALT, low all phos. EXTREMELY HIGH BILIRUBIN. elevated serum copper.
- INR >2.
- Rapid onset of hepatic coma.
- serum ceruloplasmin is unreliable.
Ratios: if All phos:T bill <4, and AST: ALT >2.2: very sensitive and specific for Wilson’s disease.

Question 10

Wilson’s disease treatment

Answer 10

• Copper chelation: D-penicillamine and Trientine.
  -Prevent absorption: zinc acetate.
• low copper diet: avoid chocolate, liver, shellfish, mushrooms.
  Antioxidants: give Vitamin D and Coenzyme Q

Question 11

Wilsons disease treatment strateies

Answer 11

Symptomatic: 1st line= chelating agents.
- after stabilization: chelators or zinc therapy. Liver only presentation: better outcomes with chelation.
If neurological symptoms: 25% of dose and increase each 4-7 days.
No symptoms: either chelators (3/4 dose) or zinc.
NEVER STOP TREATMENT UNLESS THEY HAVE RECEIVED A LIVER TRANSPLANT.
Siblings: 1 in 4 risk and parents 1 in 180 risk: MUST BE TESTED.