To understand the implication of this disease you need to understand what alpha-1-antitrypsin does.
Alpha-1-antitrypsin (AAT)
It is a protein which acts as a suicide inhibitor of elastase in vivo (Called antitrypsin bc it inhibits trypsin in vitro which i guess is what they assumed in did in vivo)
Elastase is a protease released by neutrophils in the acute phase of inflammation and meant to destroy bacteria but also has the potential to destroy your tissue. This is why we need Alpha-1-antitrypsin, to reduce the ability of the elastase to chew through tissue.
AAT is a SERPIN (serine protease inhibitor), and both trypsin and elastase are serine proteases
AAT is produced in the liver and secreted into the bloodstream where it diffused into tissues and just sits, waiting to suicidally inhibit the elastase.
AAT Deficiency (AATD)
The lungs have lots of inflammation over an individuals lifetime, Smoking causes even more. WIthout AAT elastase eats through the lung tissue uninhibited. Emphysema occurs in smokers early and emphysema can occur in non smokers early too but later than smoking
Symptoms:
- Lung Emphysema This from elastase eating through the lungs
- Liver Cirrhosis This is because the hepatocyte (liver cells) cannot release the AAT from the cells, leading to cell death
Genetics of AATD
There are different genes to make AAT and the alleles are the M, S and Z isoforms.
M is the normally functioning wild type gene, S is reduced function and Z is reallt reduced, This chart shows combination of these alleles and the risk associated,
Testing
You can perform Immunoelectrophoresis and Isoelectricfocusing on plasma/serum to assess amount on protein
Treatment of AATD
- Reduce environmental damage
- Genetic councilling for the inheritance pattern
- Exercise
- IV AAT augmentation
- Liver and lung transplant