Alpha-1 Antitrypsin Deficiency

In the early sixties, Dr. Sten Erikkson was working in his home country of Denmark trying to discover why it was that patients who were relatively young were presenting with symptoms of severe Chronic Obstructive Pulmonary Disease (COPD), a term that includes bronchitis and emphysema. Despite rather limited resources at the time, Dr. Eriksson discovered that a group of patients appeared to have low levels of a protein circulating in their blood. He called this protein Alpha-1 Antitrypsin. These days researchers tend to call this protein Alpha1 Proteinase Inhibitor. Here we will call it AAT. This protein is made in the liver, and the levels found in someone normal usually varies between 1.1 grammes / litre and 2.1 grammes / litre of blood. One of the most important jobs this protein carries out is to protect delicate lung tissue against substances released by white blood cells. If we have a chest infection these white cells, called neutrophils, are able to move through cellular walls to kill bacteria and clean up other debris. To do this the neutophil releases an enzyme called neutrophil elastase. This enzyme is able to dissolve Elastin which is the tissue that makes up the structure of the lung, allowing it to inflate and deflate as we breathe.Normally, this process is controlled by the liver releasing more AAT, which neutralises the enzyme before it can cause too much damage to the lung.

In people with A1AD there is a fault in a gene that is on chromosome 14. This fault causes the AAT protein to be mis-shaped and it has been shown that the molecules of the protein stick together to form "polymers". This malformed protein becomes "stuck" in the liver and cannot get into the blood stream.

To have A1AD means that you have inherited a faulty gene from both parents so that both chromosome 14's have the faulty gene. This is the highly deficient state where blood levels show that less than 20% of normal levels are circulating in the blood. There are many subtle differences in the gene that makes AAT. It is said to be "polymorphic" and up to 100 different types of AAT have been documented.