Alpha-1 Antitrypsin Deficiency

Alpha-1 antitrypsin (AAT) is a protein normally found in the lungs and the bloodstream. It helps protect the lungs from the damage caused by inflammation that can lead to emphysema and chronic obstructive pulmonary disease (COPD). People whose bodies do not produce enough of this protein (AAT deficiency) are more likely to develop emphysema and to do so at a younger-than-normal age (30 to 40 years old). AAT deficiency is a rare disorder and is the only known genetic (inherited) factor that increases your risk of developing COPD.

Alpha-1 antitrypsin deficiency is caused by a change, or mutation, in the gene that tells the body how to make alpha-1 antitrypsin. There are many kinds of possible changes in this gene, but only a few cause problems. To have this condition, you have to get the changed gene from both parents.

If you receive only one changed gene, you do not have the disease but are a carrier. The good copy of the gene you received from your other parent is enough to tell your body how to properly make alpha-1 antitrypsin. Some people who carry the changed gene may have very mild symptoms of the deficiency.

Treatment for alpha-1 antitrypsin deficiency involves avoiding substances—especially cigarette smoke—that could harm your lungs. Also try to avoid dust and workplace chemicals. You also may want to avoid alcohol because of the risk of liver damage. Exercise can improve your stamina and overall health. You may also need medicines and other treatments to help you breathe easier and stay as healthy and strong as you can.

The only treatment available for the lack of the protein is plasma containing alpha-1 antitrypsin. This is usually given only to people who have very low levels of AAT in their blood. It is not clear that this treatment is any better than avoiding smoke and other lung-damaging chemicals. The plasma is made from the blood of many donors and is treated to reduce the chance of spreading an infectious disease. You receive the plasma through an IV, usually every 3 to 4 weeks for life.

Your doctor may suspect you have an AAT deficiency if you:

• Develop emphysema at 45 years of age or younger.
• Develop emphysema without having any recognized risk factors, such as smoking or inhaling industrial dust or chemical fumes over a long period of time.
• Develop emphysema, and X-rays show less density in the lungs than normal (basilar hyperlucency).
• Develop unexplained liver disease.
• Have a family history of emphysema, bronchiectasis, liver disease, or inflammation of the fat under the skin (necrotizing panniculitis).
• Have bronchiectasis without an evident cause. Healthwise

It is extremely important that you do not smoke if you have an AAT deficiency. Smokers with this condition may suffer devastating disease at a young age. People with this condition who have never smoked usually do not have significant symptoms at any age.

Treatment for COPD may include medicines to help you breathe easier. It may also include pulmonary rehabilitation. This means learning exercise, eating, and breathing tips and other ways to help yourself stay as healthy and strong as you can. And your doctor may suggest that you have injections of man-made alpha-1 antitrypsin protein (also called an alpha-1 proteinase inhibitor) that has been obtained from human plasma. Examples include Aralast, Prolastin, and Zemaira. To be considered for this treatment, you must meet the following guidelines:

• Your blood levels of the alpha-1 antitrypsin enzyme are less than 11 µmol/L (micromoles per liter).
• DNA testing shows that your body does not produce enough of the enzyme or produces an enzyme that does not work properly.
• You do not smoke or have stopped smoking.
• You have difficulty breathing because of COPD or emphysema.

Injections of replacement alpha-1 antitrypsin are given either weekly or every 2 to 4 weeks. Benefits of the therapy are not clear at this time.