Wilson's Disease + AAT1 Deficiency (Dbouk)

Question 1

Inheritance pattern of Wilson’s Disease?

Answer 1

AR

Question 2

Target Organs (Major) of Wilson’s Disease?

Answer 2

Liver (Chronic hep, Cirrhosis)
Brain (Basal Ganglia, Psych)
Kidneys (Proximal tubular disease)

Question 3

Pathophys of Wilson’s disease?

Answer 3

reduced or absent expression of ATP7b leads to reduced Cu excretion into bile and inability to incorporate Cu into ceruloplasmin

Question 4

Cu is absorbed in:

Answer 4

duodenum and proximal small intestine

Question 5

95% of plasma Cu is bound to:

Answer 5

ceruloplasmin

Question 6

In Wilson’s disease, how is Cu distributed?

Answer 6

high levels of Cu in liver
high levels of free Cu in plasma
low ceruloplasmin

Question 7

Clinical features of Wilson’s?

Answer 7

1. liver disease
2. neurological disease (Parkinson’s-like)
3. psych disease
4. other organs: cardiomyopathy, pancreatitis, osteoporosis, arthritis, nephrolithiasis
5. Kayser - Fleischer Ring (maybe)

Question 8

What is a serious complication of WIlson’s?

Answer 8

fulminant liver failure

Question 9

When to suspect Wilson’s Disease:

Answer 9

• Any patient < 40 yrs with elevated AST/ALT
• Neuropsychiatric disease with liver disease
• Any young patient with liver failure

Question 10

Diagnosis of Wilson’s?

Answer 10

low ceruloplasmin with high free Cu

Kayser - Fleischer Ring

Question 11

Treatment of Wilson’s Disease?

Answer 11

1. Chelating agents
	Penicillamine
	Trientene**
	Tetrathiomolybdate
2. Zinc
3. Liver Transplantation

Question 12

Function of Alpha 1 anti-trypsin?

Answer 12

Neutralizes neutrophil elastase activity (to prevent structural abn)

Question 13

Pathophys of A1AT Deficiency?

Answer 13

Mutated Z molecule cannot be secreted by liver, leads to:

• low A1AT in serum and lung
• excess A1AT in liver

Question 14

A1AT Deficiency phenotypes associated with liver disease?

Answer 14

ZZ type and some SZ type

Question 15

When to suspect A1AT Deficiency?

Answer 15

• Cirrhosis of undetermined etiology
• Emphysema with liver disease
• Emphysema (especially in non smokers)

Question 16

Dx of A1AT?

Answer 16

• Phenotype (ZZ)

- Liver Biopsy showing Alpha 1 AT granules

Question 17

How does Liver Transplantation benefit pt’s w/ Wilsons? w/ A1AT deficiency?

Answer 17

Wilson’s Disease:

• cures the disease, No recurrence
• Neurological disease may improve

Alpha 1 Antitrypsin Deficiency:

• cures the hepatic disease
• Emphysema is irreversible (but further pulmonary damage may be prevented)