Alpha-1 antitrypsin deficiency (AATD) is a rare hereditary disease. Incorrect genetic information leads to a deficiency in the production of a certain protein (proteinase inhibitor, Pi) of varying severity. The most important substance for protection of the lungs is alpha-1 antitrypsin (AAT), which is produced in the liver. It prevents another protein (neutrophil elastase), which is produced predominantly by white blood cells and some cells in the lungs, from attacking and destroying the walls of the air sacs in the lungs (alveoli). Because the genetic information in alpha-1 patients is defective, they have less protective proteins in their blood, i.e. their plasma alpha-1 antitrypsin levels are reduced.

1. Normal AAT levels keep neutrophil elastase in check.
AAT inhibits excess elastase; lung structure preserved.

2. Neutrophils mobilize, delivering elastase at the alveolar surface in
response to bacterial infections, environmental pollutants, or tobacco exposure.

3. Low levels of AAT leave lung tissue unprotected.
Excess elastase cannot be neutralized; lung elastin destroyed; lung function compromised.

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A primer in genetics
Because every individual possesses two copies of his genetic information, there are

• people with two defective alleles (homozygous defect type) and
• people with one healthy and one defective allele (heterozygous defect type).

A number of variants of one and the same disease can therefore exist. This means that not every patient with an alpha-1 defect will develop pulmonary disease, for example. A distinction is made between several so-called genotypes of alpha-1 antitrypsin deficiency.

The most common consequence of alpha-1 antitrypsin deficiency is pulmonary disease. In addition, about 10% of people with this (homozygous) defect type develop liver disease in early childhood. This can lead to the most severe form of liver cirrhosis (shrinkage of the liver) but in most cases heals without consequence. In adults involvement of both the lungs and the liver is possible but rare.

Alpha-1 pulmonary emphysema
If alpha-1 antitrypsin is reduced, dysfunctional or completely absent, neutrophil elastase is able to attack the walls of the air sacs in the lungs unhindered and destroy their elasticity: they become “limp pockets” that collapse with every exhaled breath. There is a reduction of healthy lung tissue and a pulmonary emphysema develops: the air sacs are no longer able to perform gas exchange (where carbon dioxide is traded for oxygen), resulting in an inadequate supply of oxygen to the body.