Alpha-1 Antitrypsin deficiency

Question 1

What is alpha-1-antitrypsin deficiency

Answer 1

Genetic disorder with low A1AT (a serine protease inhibitor (serpinopathy)), which normally helps in inflammatory cascade control

Question 2

Alpha-1-antitrypsin deficiency genetics

Answer 2

Typed by electrophoretic mobility (medium (m), slow (s), very slow (z))
PiMM is normal, PiZZ is high risk, PiSZ/PiMZ have low risk of liver disease

Question 3

Alpha-1-antitrypsin deficiency presentation

Answer 3

In adults more lung symptoms so emphysema (damage from neutrophil elastase)
In children liver presentations, so cirrhosis/cholestatic jaundice

Question 4

Alpha-1-antitrypsin deficiency tests

Answer 4

Phenotyping using isoelectric focusing electrophoresis

Low serum A1AT, can be hidden by inflammation as A1AT is an acute phase protein
Lung function tests - obstructive pattern + reduced FEV1
Liver biopsy - Periodic Acid-Schiff stain positive for lymphocytes, diastase resistant globules

Prenatal Dx with DNA analysis of chorionic villus at 11-13 weeks gestation

Question 5

Alpha-1-antitrypsin deficiency management

Answer 5

Smoking cessation
Treat lung infections
Liver transplantation in decompensated cirrhosis
Lung transplant

Inhaled A1AT has been tried, not routinely used
IV A1AT pooled from plasma is expensive but may work (weak evidence)

Question 6

Alpha-1-antitrypsin deficiency prognosis

Answer 6

Very variable, worse if male/smoker/obese
Emphysema is cause of death in most, liver disease in 5%
>50 yrs, cirrhosis ± HCC affects 25% of A1AT deficient