Aplha-1 antitrypsin deficiency

Question 1

Genetics?

Answer 1

Autosomal recessive defect of ALAT on chromosome 14

Question 2

Cause?

Answer 2

Inherited deficiency of alpha-1 antitrypsin (protease inhibitor) leading to excess protease enzymes that damage the liver (cirrhosis, HCC) + lungs (emphysema)

Question 3

Without alpha-1 antrypsin what happens?

Answer 3

ALT1 inhibits neutrophil elastase which digests connective tissue. Neutrophil elastase then destroy alveoli etc.

Question 4

What does is lead to? what age?

Answer 4

(1) Liver cirrhosis >50

(2) Pulmonary basal emphysema >30

Question 5

Presentation?

Answer 5

(1) COPD presenting between 30-40
(2) Neonatal jaundice at birth
(3) Derranged LFTs in adults, no identified cause

Question 6

Screening test?

Answer 6

serum alpha-1 antitrypsin

Question 7

What does a liver biopsy show?

Answer 7

acid-Schiff-positive staining globules

Question 8

How would you diagnose emphysema?

Answer 8

High resolution CT thorax

Question 9

Management?

Answer 9

(1) stop smoking - rapidly accelerates
(2) NICE against IV A1AT
(3) Organ transplant - decompensation/severe