genotypic

What is alpha-1 antitrypsin deficiency (AAT deficiency)?

Alpha-1 antitrypsin deficiency (AAT deficiency, or AATD) is an inherited condition that raises your risk for lung and liver disease. If you have this condition, your body doesn't make enough alpha-1 antitrypsin (AAT).

AAT is made by your liver. It helps protect your lungs from inflammation and irritating substances you might breathe in, such as smoke. If your liver doesn't make enough AAT, your lungs may be more easily damaged from smoking, pollution, or dust from the environment. This can lead to a serious lung condition called chronic obstructive pulmonary disease (COPD). AAT deficiency may also cause a liver disease called cirrhosis. This is more common in children who have AAT deficiency.

What causes alpha-1 antitrypsin deficiency (AAT deficiency)?

AAT deficiency is a genetic disorder. That means it's caused by changes in your genes, which may also be called gene variants or mutations.

Your genes carry information that controls what you look like and how your body works. AAT deficiency is caused by changes in the SERPINA1 gene, which carries instructions for making the AAT protein. These gene changes are inherited from your parents, so AAT deficiency tends to run in families:

• If you have two mutated copies of the gene, it means you have a condition called AAT deficiency. People with this disorder have a higher risk of getting lung disease or liver damage before the age of 45.
• If you have one mutated copy of the gene, you are a carrier of AAT deficiency. In these cases, this means you are at slightly higher risk of developing lung disease, especially if you have other risk factors, such as being a smoker. You could still pass the mutated gene on to your children.

There are a few gene changes that cause AAT deficiency. These gene changes can:

• Decrease the amount of AAT protein your liver makes.
• Prevent your liver from making any AAT.
• Affect the shape of the AAT protein so that it can't move out of your liver to protect your lungs. Over time, AAT builds up in your liver and causes damage.

What are the symptoms of alpha-1 antitrypsin deficiency (AAT deficiency)?

Some people who have AAT deficiency do not have any symptoms. For those who do, symptoms usually appear in people between 20 and 50 years old. These symptoms may include:

• Wheezing
• Shortness of breath, especially after exercise
• Chronic cough with phlegm (mucus)
• Repeated respiratory infections such as colds and the flu
• Chest pain
• Fatigue
• Faster-than-normal heartbeat when you stand up
• Vision problems
• Losing weight without trying

Some people who have AAT deficiency may have liver damage. Signs of liver damage include jaundice (a condition that causes your skin and eyes to turn yellow) and swelling in your legs.

Rarely, AAT deficiency can cause skin problems, such as painful lumps or patches.

How is alpha-1 antitrypsin deficiency (AAT deficiency) diagnosed?

Your health care provider may test you for AAT deficiency if you have:

• Symptoms of AAT deficiency
• A condition that could be related to AAT deficiency
• Relatives who have AAT deficiency
• Relatives who have a lung or liver disease that could be related to AAT deficiency

AAT deficiency in babies often affects the liver. Your baby may need AAT testing if he or she has signs of liver disease such as jaundice or abnormal liver enzyme tests.

A blood test can check the level of AAT protein in your blood. If the level is lower than normal, it is likely that you have AAT deficiency.

A genetic test is the most certain way to check for AAT deficiency and should be done to confirm the results of the blood test. There are two types of genetic tests:

• A genotype test looks for the more common types of gene changes that can cause AAT deficiency.
• A phenotype test checks for changes in the AAT protein that change how it would normally work.

If your lungs are affected, you may also have lung function tests to see how well your lungs are working.

What are the treatments for alpha-1 antitrypsin deficiency (AAT deficiency)?

There is no cure for AAT deficiency, but there are treatments to help with the symptoms and slow the lung damage it causes. Treatment options may include:

• Inhaled medicines to help you breathe better.
• Pulmonary rehabilitation.
• Oxygen therapy.
• Augmentation therapy, which is a lifelong treatment. It raises the levels of the AAT protein in your lungs, using ATT protein taken from the blood of donors. It helps slow down lung damage. It cannot prevent liver damage.
• Lung surgery or a lung transplant, if your lungs are severely damaged.
• Liver transplant, if your liver is severely damaged.

To help prevent or delay lung damage, it is important to quit smoking (if you smoke) and avoid secondhand smoke, dust, and air pollution. Ask your provider If you need to stop drinking alcohol.