This information is being provided to help you understand AAT deficiency (or alpha-antitrypsin deficiency). Some of the terms may be confusing at first. This information is not a substitute for your doctor. If you have questions about this information, don't hesitate to ask him or her.

What is AAT?

Alpha-antitrypsin (which we will call AAT) is a protein that circulates in your blood. It is also called "alpha-proteinase inhibitor" by some scientists. Most of the AAT in your blood is made in your liver. AAT protects the tissues of your body from being damaged by substances contained in white blood cells.

Why is AAT important?

White blood cells contain substances ("enzymes") that help them to move through tissues, clean up wounds, and perform other valuable, healthy functions. However, the activities of these substances must be strictly controlled, or they can attack normal tissues in your body. AAT normally provides one type of protection against these enzymes.

What is AAT deficiency?

AAT deficiency is an inherited condition in which the AAT produced by your body is different from most people's. If you have AAT deficiency, your AAT works nearly as well as the normal type, but the amount in your blood is very low. Most people have 7 to 10 times more AAT in their blood than people who have AAT deficiency.

How can AAT deficiency be harmful?

Lung problems: The structure of the lung is very delicate. White blood cells are always present in the lungs, where they remove dust, fight infections, and perform other valuable functions. However, the substances released by white blood cells can damage the tiny air sacs in the lungs when the protection from AAT is less than normal.

Over many years, the tiny air sacs often break down in people who have AAT deficiency, and emphysema results. The lung works less efficiently if this happens, and breathing becomes difficult. Medical science has not yet found a way to reverse this problem. If you have AAT deficiency, you and your doctor will want to be especially careful to protect your lungs.

Liver problems: AAT is made in your liver. AAT deficiency causes a mild strain on your liver, which may or may not cause noticeable health problems. People with AAT deficiency may develop liver problems, either just after birth or later, beginning in middle age. Your doctor may want to do some tests to check on your liver.

How is AAT deficiency inherited?

AAT deficiency is caused by a pair of genes. One of these genes is inherited from each of your parents. A person has the disease only if he or she inherits two genes for AAT deficiency.

People who have only one gene for AAT deficiency do not have the disease, but they are "carriers" of the deficiency. Their AAT levels are usually lower than normal, but this does not cause a serious risk of health problems. If you have AAT deficiency, both of your parents are probably carriers. When a carrier has children with someone who also carries the gene, any of their children could inherit two of the abnormal genes (and thus have AAT deficiency). The brothers and sisters of people with AAT deficiency have a one-in-four chance of also having two deficiency genes, and therefore having AAT deficiency.

The great majority of people in the United States have two normal genes for AAT. If you have AAT deficiency, the chances are very great that your partner has two normal genes. You will pass on one gene for the deficiency to each of your children, but they will be carriers and will not have AAT deficiency. The exceptions to this rule occur if one of your children also gets a gene for the deficiency from your partner. It may be appropriate to test your partner to see if he or she is a carrier, because about three out of every hundred people in the United States are (see "Testing for AAT Deficiency").

You should consider informing your family members, especially since each of your brothers and sisters has a one-in-four chance of also having AAT deficiency. The AAT Deficiency Detection Center (www.alphatest.net) can test your family members if they contact us (confidentially, if they wish), or their doctors may contact us. If they decided to be tested, they should have a test that detects carriers ("phenotyping" or "genotyping").

Why do some people with AAT deficiency become ill, while others appear healthy?

There are only partial answers for this important question. In some people with AAT deficiency, other factors contribute to lung problems. The most important ones known are smoking, asthma, and lung infections. Medical research is trying to find other things that contribute to lung problems in AAT deficiency. The Alpha One International Registry is trying to provide answers to these questions by studying families of people with AAT deficiency.

We have little information about the underlying causes of variability in liver problems in AAT deficiency, but most people do not develop serious liver disease.

It is possible for some people with AAT deficiency to live a full, normal life, especially if they do not smoke, but they should take special care of their lungs, have periodic health check-ups, and notify their doctors of any new symptoms.

What medical tests should I have?

You should discuss this question with your doctor. Besides the usual examination, he or she may ask for special tests of your lungs and liver. These could include breathing tests, chest X-rays, a CT scan of your chest, tests of the amount of oxygen in your blood (another test of your lung function), and other blood tests including tests of liver function.

Your doctor may want to repeat these tests over time to track your progress or to monitor the effects of treatment.

What about smoking?

If you have AAT deficiency, you absolutely must not smoke! If you are smoking now, stop immediately! If you have difficulty quitting, get help from your doctor. Medications and smoking cessation programs have been shown to help people quit. If you don't smoke, don't start. Staying away from cigarettes is the single most important thing that you can do to preserve your health.

Remember, if you have AAT deficiency you have a special reason to quit. Smoking attracts white blood cells to the lungs in large numbers, and speeds the development of lung disease.Remember that your lungs do not have normal defenses against the substances contained in white blood cells.

There are many ways to quit smoking. Work out a plan with your doctor. Your local branch of the American Lung Association can also help you. Try again if you don't succeed in quitting on the first attempt. Many successful quitters fail the first time they try. As a group, people with AAT deficiency are quite successful in quitting.

Is there treatment for AAT deficiency?

General measures: If you have lung problems, your doctor may prescribe medicine to help your lungs function and to reduce the number of white blood cells in your lungs. If you have asthma, it is especially important to control it. Call your doctor at the first sign of a chest cold or other chest infection, since white blood cells come into the lungs to fight these infections. Your doctor may want to vaccinate you against influenza and pneumonia. Receiving extra oxygen to breathe can be lifesaving for people whose blood oxygen is low. Your doctor may want to recommend an exercise plan or exercise program. Many people are helped by involvement with support groups, which can provide you with information and companionship.

Specific treatment: Augmentation therapy is now available to boost the level of AAT in your blood. This therapy, the first specific treatment for AAT deficiency, may slow or stop the progression of lung disease. The currently marketed product is called Prolastin. It must be given directly into a vein at regular intervals. Alternative products are now being developed, and some of them are being actively studied or are awaiting approval from the Food and Drug Administration.

What is augmentation therapy?

Augmentation therapy provides you with AAT that has been purified from the blood of other people. Prolastin is a concentrated form of AAT that has been derived from human blood, then packaged in a form that is stable until it is used. It is normally given once a week. It increases the AAT in your blood to levels that should help to protect your lungs. There is no form of the product that you can take by mouth. If your doctor advises you to take Prolastin, you must receive it for the rest of your life to continually renew the supply of AAT in your blood.

Prolastin is not a cure, and it cannot reverse lung problems that already exist. It does not treat or prevent liver problems. Clinical studies have suggested that it slows the progression of lung problems in people who have moderately severe emphysema, and it may prolong life in these people.

The safety record with administration of Prolastin has been excellent. In particular, there have been no reports of getting an infection from it. The part of the blood used to make Prolastin has been tested for antibody to the AIDS virus and for hepatitis B. Prolastin is heat-treated to further decrease the risk of infection. This means that there is no reason to think that anyone could get an infection from it. However, as an additional safety measure, you should be vaccinated against hepatitis B before receiving Prolastin.

You may want to discuss Prolastin treatment with your doctor. If you do not have lung problems, or if you already have very severe lung problems, Prolastin may not be appropriate for you.