This information is being provided to help you understand alpha1-antitrypsin deficiency (Alpha-1). 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. Alpha-1 is a hereditary defect in body chemistry that affects approximately 100,000 Americans.

What is alpha1-antitrypsin?

Alpha1-antitrypsin is a protein that circulates in your blood and protects the tissues of your body from being damaged by substances contained in white blood cells. Most of the alpha1-antitrypsin in your blood is made in your liver.

Why is alpha1-antitrypsin important?

White blood cells contain substances called enzymes that help them move through tissues, clean up wounds, and perform other valuable, healthy functions. The activities of these substances, however, must be strictly controlled or they can attack normal tissues in your body. Alpha1-antitrypsin normally provides one type of protection against these enzymes.

What is alpha1-antitrypsin deficiency (Alpha-1)?

Alpha1-antitrypsin deficiency (Alpha-1) is an inherited condition in which the alpha1-antitrypsin produced by the body is different from the alpha1-antitrypsin in most normal people. Severe Alpha-1 occurs in people who have two abnormal alpha1-antitrypsin genes. If you have severe Alpha-1, your alpha1-antitrypsin 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 alpha1-antitrypsin in their blood than you have in yours.

You could also have a milder form of Alpha-1, in which you have one normal and one abnormal alpha1-antitrypsin gene. In this situation, the amount of alpha1-antitrypsin in your blood is less severely reduced, and sometimes is even normal.

Finally, you could have one or two abnormal alpha1-antitrypsin genes of a type that is more rare. This is a special type of hereditary abnormality that will require explanation by your doctor.

How can Alpha-1 be harmful?

Lung problems: The structure of the lung is very delicate. White blood cells are always present in the lungs: 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 provided by alpha1-antitrypsin is less than normal.

Over many years, the tiny air sacs often break down in people who have Alpha-1, resulting in emphysema. The lungs work less efficiently if this happens and breathing becomes difficult. Medical science has not yet found a way to reverse this problem. If you have Alpha-1, you and your doctor will want to be especially careful to protect your lungs.

Liver problems: alpha1-antitrypsin is made in your liver. This causes a mild strain on your liver, which may or may not cause noticeable health problems. People with Alpha-1 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 Alpha-1 inherited?

Everyone has two genes for alpha1-antitrypsin, one of which was derived from each parent. A person has severe Alpha-1 if he or she inherits two abnormal genes for Alpha-1.

People who have only one abnormal gene for Alpha-1 have alpha1-antitrypsin levels in their blood that are usually lower than normal. Unless they have a smoking history, these people have a lower health risk than those who have severe Alpha-1.

Anyone who has an abnormal alpha1-antitrypsin gene has a 50% chance of passing that gene on to each of his or her children. When a person who has one abnormal gene has children with someone who has an abnormal gene, any of their children could inherit two of the abnormal genes (and thus have severe Alpha-1). The brothers and sisters of people with severe Alpha-1 have a one-in-four chance of also having two abnormal genes, and therefore of also having severe Alpha-1.

The great majority of people in the United States have two normal genes for alpha1-antitrypsin. If you have two abnormal alpha1-antitrypsin genes, the chances are very great that your partner has two normal genes: you will pass on one abnormal alpha1-antitrypsin gene to each of your children, but they will not have severe Alpha-1. The exceptions to this rule occur if one of your children also gets a gene for Alpha-1 from your partner. It may be appropriate to test your partner to see if he or she has an abnormal alpha1-antitrypsin gene. About three out of every hundred people in the United States do have an abnormal alpha1-antitrypsin gene.

If you have severe Alpha-1, you should consider informing your family members, especially since each of your brothers and sisters has a one-in-four chance of also having severe Alpha-1. If you have only one abnormal alpha1-antitrypsin gene, your family members should also be tested, since that gene runs in your family. If they decide to be tested, they should have a phenotyping or genotyping test that specifically detects abnormal genes.

Why do some people with Alpha-1 become ill, while others appear healthy?

There are only partial answers for this important question. In some people with severe Alpha-1, factors in addition to their Alpha-1 contribute to lung problems. The most important known factors are smoking, asthma, and lung infections. Medical research is trying to find other factors that contribute to lung problems in severe Alpha-1. People who have only one abnormal alpha1-antitrypsin gene tend to stay healthy unless they have a smoking history.

We have little information about the underlying causes of variability in liver problems in severe Alpha-1, but most people do not develop serious liver disease. People who have only one abnormal alpha1-antitrypsin gene develop liver problems only rarely.

It is possible for some people with even severe Alpha-1 to live a full, normal life, especially if they do not smoke. It is important, however, that they 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 Alpha-1, 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 Alpha-1, you have a special reason to quit smoking. Smoking attracts white blood cells to the lungs in large numbers and speeds the development of lung disease. With Alpha-1, your lungs do not have normal defenses against the substances contained in white blood cells.

Is there treatment for Alpha-1?

General Measures: If you have lung problems, your doctor may prescribe inhaled 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 program. Many people are helped by involvement with support groups, which can provide you with information and companionship.

Specific Treatment: Augmentation therapy is available to boost the level of alpha1-antitrypsin in your blood. This therapy, the first and only available specific treatment for Alpha-1, may slow or stop the progression of lung disease.

What is augmentation therapy?

If you have severe Alpha-1, augmentation therapy can provide you with alpha1-antitrypsin that has been purified from the blood of many donors. It has been approved as a specific treatment for Alpha-1 by the US Food and Drug Administration, and is administered into one of your veins in a dose calculated from your body weight. Because your body gradually breaks down the alpha1-antitrypsin that you receive, repeated doses are necessary. Generally, people with Alpha-1 receive weekly doses of augmentation therapy to sustain an adequate amount of alpha1-antitrypsin in their blood.

Many thousands of people with Alpha-1 have received augmentation therapy since it was first approved for use in 1988. Augmentation has been shown to be safe and side effects are negligible, or mild and tolerable, for most people. It is usually given by a visiting nurse or family member in the home, but depending on individual circumstances, other people with Alpha-1 receive it in a hospital or infusion center. Regardless of where you receive it, the inconvenience of repeated treatments can be minimized.

If you have Alpha-1 and lung symptoms, your doctor may want to discuss augmentation therapy with you.