Alpha-1 Antitrypsin Deficiency

Is Testing Right for Me? I Have My Test Results

Alpha-1 Antitrypsin Deficiency

What Is Alpha-1 Antitrypsin Deficiency?

Alpha-1 antitrypsin deficiency (pronounced "alfa-one anti-trip-sin") is a genetic disease than can cause lung and liver problems. Often called Alpha-1, this condition is caused by low levels of a protein in the blood called alpha-1 antitrypsin (AAT).

Normally, the AAT protein is made in the liver and then released into the blood stream. AAT is most important in the lungs and the liver.  Its role is to protect against enzymes that break down cells. When AAT is low or missing, the elastic tissue in these organs becomes damaged and can't work as well. This causes lung and liver disease and sometimes other health problems.  

Signs and Symptoms

Alpha-1 lung disease is usually the first symptom. It is most often misdiagnosed as asthma.  It tends to show up when people are in their 20s or 30s, but symptoms can develop at any age. Liver disease affects a smaller percentage of people with Alpha-1. The risk of liver problems increases over time. Other factors — both genetic and environmental — often play a role in whether someone develops lung or liver disease. 

Signs and symptoms of Alpha-1 lung disease:

  • Difficulty breathing or wheezing
  • Chronic cough
  •  Excess phlegm (mucus)
  • Frequent lung or sinus infections 
  • Asthma that can't be treated completely, even with medicine 
  • Bronchiectasis (chronic inflammation of the lungs) without a known cause 
  • Emphysema or chronic obstructive pulmonary disease (COPD)

Signs and symptoms of Alpha-1 liver disease:

  • High liver enzymes on lab testing
  • Yellow or bronze color of the skin or eyes (jaundice)
  • Hardening of the liver due to build-up of scar tissue (cirrhosis)
  • Liver cancer
  • Unexplained liver disease at any age

There are also two rare conditions associated with Alpha-1. Necrotizing panniculitis is a treatable skin condition in which painful, red lumps appear on the thighs that can develop into ulcers and dead tissue. Anti-proteinase 3-positive vasculitis (or C-ANCA) is an inflammation of blood vessels or lymph nodes.

Next: Who Is At Risk for Alpha-1 Antitrypsin Deficiency?

Why are you considering genetic testing?

I think I might have Alpha-1, but I haven't seen a doctor yet.

I probably have Alpha-1 but have not yet had genetic testing.

I have a family member with definite or possible Alpha-1.

My partner has Alpha-1 or is a known carrier, and we want to know the risks for our children.

The symptoms you may feel from Alpha-1 Antitrypsin Deficiency are very similar to symptoms caused by many different breathing conditions. People with symptoms of breathing or liver problems may need lab tests, imaging, breathing tests, and other tests to help a doctor find the likely cause of those symptoms.

Genetic testing shouldn't be considered until all of the other common causes have been ruled out.

When testing finds two mutations, the results confirm that you have Alpha-1 antitrypsin deficiency. Knowing information about your Alpha-1 mutations can provide you with information to treat your condition and prevent complications. Your results give you information to:

  • Make informed choices about health care, lifestyle, career, and family planning
  • Take steps to slow the progression of Alpha-1
  • Avoid harmful behaviors such as smoking and alcohol consumption
  • Modify your exposure to environmental factors such as dust, pollution, and certain chemicals
  • Start appropriate treatments
  • Identify relatives who may also be at-risk for having Alpha-1
    • Your brothers and sisters would have the highest chance to also have the disease. There is a chance for other relatives as well because of how common carriers are

When testing doesn't find a mutation, the results don't completely rule out that you have Alpha-1 antitrypsin deficiency. Genetic testing cannot find all of the gene mutations that cause Alpha-1 Antitrypsin Deficiency. Additional testing, such as protein testing or gene sequencing, may be helpful if your doctor thinks the chances are very high that you have Alpha-1 even when your test results are normal.

If you have a family member with Alpha-1, your chances to have it are higher. The chance is highest if your brother or sister has Alpha-1. The first person in the family to have genetic testing should be someone most likely to have Alpha-1. If your relative(s) that might have Alpha-1 aren't available or willing to have genetic testing, you can have testing but the meaning of your results may be less clear.

  • When testing finds two mutations, you can be certain that you have inherited Alpha-1. The symptoms of Alpha-1 can be different between people in the same family. Some people have the mutations but never get symptoms at all. So, your results don't necessarily predict your future but they do mean that you need may need screening tests to check your lungs and liver. Your results give you information to:
    • Make informed choices about health care, lifestyle, career, and family planning
    • Take steps to slow the progression of Alpha-1
    • Avoid harmful behaviors such as smoking and alcohol consumption
    • Modify your exposure to environmental factors such as dust, pollution, and certain chemicals
    • Start appropriate treatments
    • Identify other relatives who may also be at-risk for having Alpha-1
  • When testing finds one mutation, you are a carrier of Alpha-1. The chance for you to develop lung or liver problems is low, especially if you don't smoke. However, you have a higher chance to have a child with Alpha-1. You may wish to consider carrier testing for your partner. If both parents are carriers, there is a 1 in 4 (25%) chance with each pregnancy to have a child with Alpha-1.
  • When testing doesn't find a mutation, there are two possible explanations – you may not have inherited either of the mutations that cause Alpha-1 in your family or the mutation that causes Alpha-1 in your family can't be found with the test that was done. In this situation, a normal result doesn't rule out the chance that you are an Alpha-1 carrier. However, it is very unlikely that you have Alpha-1 or are a carrier. Genetic testing finds about 95% of the mutations that cause Alpha-1.

If you don't have a family history of Alpha-1, the chance for you to be a carrier is between 1 in 10 and 1 in 33. The chances may be lower if your ancestors are not from Europe.

  • When testing finds a mutation, then you are a carrier of Alpha-1.
    • If your partner has Alpha-1, the chance for you to have a child with Alpha-1 is 1 in 2 (50%) with each pregnancy.
    • If your partner is a carrier of Alpha-1, the chance for you to have a child with Alpha-1 is 1 in 4 (25%) with each pregnancy.
    • Prenatal diagnosis is possible for Alpha-1. However, this testing is not useful for telling how mild or severe the disease might be, or when a child might begin to have symptoms. The chance for health problems in childhood is low.
  • When testing doesn't find a mutation, then the chance for you to be a carrier is very low. Testing detects about 95% of the mutations that cause Alpha-1. You are at a very low risk to have a child affected by Alpha-1.