Inherited Liver Disease (Wilson's, Haemochromatosis, a1 antitrypsin)

Question 1

What is Wilson’s disease?

Answer 1

AR defect in copper metabolism (gene ATP7B)

Question 2

Pathology of Wilson’s disease?

Answer 2

Decreased biliary excretion of copper, decreased incorporation of copper into ceruloplasmin.

Question 3

Liver manifestations of Wilson’s disease?

Answer 3

• Acute hepatitis
• Fulminant liver failure
• Chronic active hepatitis
• Low risk of HCC

Question 4

What are the clinical manifestations of Wilson’s disease?

Answer 4

ABCD
Asterixis
Basal ganglia degeneration (suspect if PD Sx in young)
Ceruloplasmin decrease
Cirrhosis
Corneal deposits (Kayser-Fleischer Ring)
Copper
Dementia

Question 5

What are Kayser Fleischer rings?

Answer 5

Copper deposits in Descemet’s membrane; more commoin in patients with CNS involvement (Wilson’s Disease)

Question 6

CNS manifestations of Wilson’s disease?

Answer 6

• Basal ganglia (wing flapping tremor, Parkinsonism)
• Cerebellum: dysarthria, dysphagia, incoordination, ataxia
• Cerebrum: psychosis, affective disorder

Question 7

Kidney manifestations of Wilson’s disease?

Answer 7

• Fanconi’s syndrome: proximal tubule transport defects

- Stones.

Question 8

When should Wilson’s disease be suspected?

Answer 8

• Increased LFTs
• Clinical manifestations
• Young (

Question 9

Wilson’s disease screening tests?

Answer 9

1. Reduced serum ceruloplasmin (

Question 10

Wilson’s disease Dx tests?

Answer 10

1. Increased copper- liver Bx

2. Genetic analysis (but imperfect as many ATP7B mutations)

Question 11

Treatment Wilson’s disease?

Answer 11

4 drugs
1. Penicillinamine chelates Cu (poorly tolerated)
2. Trientine: chelates Cu
3. Zinc (impairs Cu excretion in stool, decreases absorption from gut)
4. Tetrathiomolybdate: if CNS involvement
Screen relatives
Transplant if severe

Question 12

What is haemochromatosis?

Answer 12

Excessive iron storage causing multi organ system dysfunction (esp liver) w/ total body iron stores increased to 20-40g (normal 1g)

Question 13

What is primary haemochromatosis?

Answer 13

Recessive gene (HFE) results in ongoing gut absorption of iron despite adequate iron stores. Mutation not 100% penetrant (i.e. not all homozygotes have clinical iron overload)

Question 14

What is secondary haemochromatosis?

Answer 14

• Parenteral iron overload (e.g. transfusions)
• Chronic haemolytic anaemia
• Excessive iron intake

Question 15

CFx haemochromatosis?

Answer 15

• Elevation LFTs
• Liver: cirrhosis, HCC
• Pancreas: diabetes, chronic pancreatitis
• Skin: bronze or grey
• Heart: dilated cardiomyopathy
• Pituitary: hypogonadotropic hypogonadism
• Joints: arthralgia

Question 16

Ix in haemochromatosis?

Answer 16

• Screening: transferring, ferritin
• HFE gene: C282Y allele
• Liver biopsy (define degree of overload, detect cirrhosis)
• HCC screening

Question 17

Rx haemochromatosis?

Answer 17

• Phlebotomy: lifelong maintenance q2-6mo

- Secondary haemochromatosis often requires chelation therapy