Alpha-1 Antitrypsin Deficiency

Question 1

What causes A1AT deficiency?

Answer 1

A lack of a protease inhibitor (Pi) normally produced by the liver (A1AT)

Question 2

What is the role of A1AT?

Answer 2

To protect cells from enzymes such as neutrophil elastase.

Question 3

What is the classical sequale/complication of A1AT seen?

Answer 3

Classically causes emphysema (i.e. COPD) in patients who are young and non-smokers.

Question 4

On what chromosome is the gene coding for A1AT located?

What is the inheritance pattern for A1AT deficiency?

Answer 4

Chromosome 14

Autosomal recessive/ co-dominant fashion

Question 5

What genotype is most often seen in patients who manifest the disease?

Answer 5

PiZZ genotype

PiMM - normal
PiSS - 50% normal A1AT
PiZZ - 10% normal A1AT

Question 6

What are the features of alpha-1-antitrypsin deficiency?

Answer 6

Lung: panacinar emphysema; most marked in lower lobes
Liver: cirrhosis and hepalocellular carcinoma in adults and cholestasis in children

Question 7

What are the investigations of A1AT deficiency?

Answer 7

A1AT concentrations

Spirometry: obstructive picture

Question 8

What is the management of A1AT deficiency?

Answer 8

No smoking
Supportive: bronchodilators, physiotherapy
Intravenous A1AT protein concentrates
Surgery: lung volume reduction surgery, lung transplantation