alpha-1 antitrypsin deficiency

Question 1

what is A1AT deficiency?

Answer 1

common inherited condition caused by a lack of a protease inhibitor (Pi) normally produced by the liver. The role of A1AT is to protect cells from enzymes such as neutrophil elastase. It classically causes emphysema (i.e. chronic obstructive pulmonary disease) in patients who are young and non-smokers.

Question 2

what type of inherited disorder is A1AT defiency?

Answer 2

located on chromosome 14
inherited in an autosomal recessive / co-dominant fashion*

alleles classified by their electrophoretic mobility - M for normal, S for slow, and Z for very slow

normal: PiMM

heterozygous: PiMZ
evidence base is conflicting re: risk of emphsema
however, if non-smoker low risk of developing emphsema but may pass on A1AT gene to children

homozygous PiSS: 50% normal A1AT levels

homozygous PiZZ: 10% normal A1AT levels

Question 3

what are features of A1AT defiency?

Answer 3

patients who manifest disease usually have PiZZ genotype
lungs: panacinar emphysema, most marked in lower lobes
liver: cirrhosis and hepatocellular carcinoma in adults, cholestasis in children

Question 4

what investigations are needed for A1AT defiency?

Answer 4

A1AT concentrations
spirometry- obstructive

Question 5

what is the management of A1AT deficiency?

Answer 5

no smoking
supportive: bronchodilators, physiotherapy
intravenous alpha1-antitrypsin protein concentrates
surgery: lung volume reduction surgery, lung transplantation