alpha-1 antitrypsin deficiency
Alpha-1 antitrypsin deficiency, or AAT deficiency, is a condition that raises the risk for certain types of lung disease, especially if a person smokes. AAT deficiency is an inherited condition, which means that it's passed in the genes from parents to children.
Some people who have severe AAT deficiency develop emphysema – often when they're only in their forties or fifties. Emphysema is a serious lung disease in which damage to the airways makes it hard to breathe.
A smaller number of people who have AAT deficiency have cirrhosis and other serious liver diseases. Cirrhosis is a disease in which the liver is scarred, preventing it from working properly. In people who have AAT deficiency, cirrhosis and other liver diseases usually occur in infancy and early childhood.
A very small number of people who have AAT deficiency have a rare type of skin disease called necrotizing panniculitis. This skin disease can cause painful lumps under or on the surface of the skin.
This article will focus on AAT deficiency as it relates to lung disease.
Alpha-1 antitrypsin is a protein made in the liver. Normally, the protein enters the bloodstream and helps protect the body's organs from the harmful effects of other proteins. One of the main organs it protects is the lungs.
AAT deficiency occurs when the AAT proteins made in the liver aren't the right shape. They get stuck inside liver cells and can't get into the bloodstream. Because not enough AAT protein travels to the lungs to protect them, the risk of lung disease increases. Also, because too many AAT proteins are stuck in the liver, liver disease can develop.
AAT deficiency is considered severe when blood levels of the AAT protein fall below the lowest amount needed to protect the lungs.
AAT deficiency is an inherited condition caused by altered genes. It's not known how many people have it. Many people who have it may not know they have it. Estimates of how many people have the condition range from about 1 in every 1,600 people to about 1 in every 5,000 people.
A person who has AAT deficiency may not have any serious complications and may live a normal lifespan. Many nonsmokers who have AAT deficiency don't develop any serious related lung diseases.
Among people with AAT deficiency who do have a related lung or liver disease, about 3% die each year. Smoking is the leading risk factor for life-threatening lung disease in an individual with AAT deficiency. In the case of severe AAT deficiency, smoking can shorten a person's life by as much as 20 years.
AAT deficiency has no cure, but there are treatments. In most cases, treatment is based on the type of disease a person develops.
Altered alpha-1 antitrypsin genes cause AAT deficiency. AAT genes tell cells in the body how to make AAT proteins.
AAT deficiency occurs when AAT proteins made in the liver aren't the right shape. These proteins get stuck in the liver cells where they are made. They can't get to the organs in the body that they protect, such as the lungs. Without the proteins protecting the organs, diseases can develop.
AAT genes are passed from parents to children. In order to be affected by AAT deficiency, a person must inherit a faulty gene from one or both of their parents. This is called an autosomal codominant inherited condition. If you inherit two faulty genes you have a 90 per cent chance of abnormal levels of A1AT If you inherit one faulty gene you are still at risk of lung and liver damage with 40% of these people having abnormal AAT levels.
Who is at risk?
In the United States, White people of western and northern European descent are more likely than other ethnic groups to have alpha-1 antitrypsin deficiency caused by the PiZ genes. Many altered genes can cause AAT deficiency, but PiZ is the most common.
Major risk factors for alpha-1 antitrypsin deficiency
AAT deficiency is an inherited condition. If you have close relatives with known AAT deficiency, you're more likely than others to have this inherited condition. Even so, it doesn't mean that you will have one of the diseases related to the condition.
Some risk factors make it more likely that you will develop lung disease if you have AAT deficiency. Smoking is the leading risk factor for serious lung disease if you have AAT deficiency. Your risk also may go up if you're exposed to dust, fumes, or other toxic substances.
Signs and symptoms
You may have alpha-1 antitrypsin (AAT) deficiency if you have signs and symptoms of serious lung disease without any obvious cause. Another sign of AAT deficiency is if you develop emphysema at age 45 years or younger.
Signs and symptoms of emphysema include:
At first, many people who have AAT deficiency are diagnosed with asthma. This is because wheezing is also a symptom of asthma. Also, people who have AAT deficiency respond well to asthma medicines.
Alpha-1 antitrypsin (AAT) deficiency is usually diagnosed after you develop a lung or liver disease that's linked to AAT deficiency.
Because of this, a number of different health care professionals may be involved in the diagnosis of AAT deficiency. These include primary care doctors, pulmonologists (lung specialists), and hepatologists (liver specialists).
To check whether the disease you have may be related to AAT deficiency, your doctor will:
If your doctor thinks that you have AAT deficiency, he or she may order tests to check for the condition. He or she also may order tests to check for lung- or liver-related conditions.
A genetic test is the most certain way to check for AAT deficiency. This
test will show whether you have altered AAT genes.
A blood test also may be used. This test checks the levels of AAT protein in your blood. If the AAT levels are a lot lower than normal, it's likely that you have AAT deficiency.
Pulmonary function tests show how well you're able to blow air out of your lungs. They also show how much air gets into your lungs when you breathe. These tests are used to check how severe your lung disease is and how well treatment is working.
High-resolution CT scanning uses X-rays to create detailed pictures of sections of the body. CT scans show whether you have emphysema and how severe it is.
Alpha-1 antitrypsin (AAT) deficiency has no cure. However, the lung diseases linked to this inherited condition have many treatments. Most of these treatments are the same as the ones given to people who have lung diseases without AAT deficiency.
If you have emphysema or other lung diseases or symptoms related to AAT deficiency, your doctor may recommend:
Augmentation therapy is a type of treatment given only to people who have AAT-related lung diseases. This therapy involves getting infusions of the AAT protein. This raises the level of the protein in your blood and lungs.
Not enough research has been done to show whether this type of therapy works. However, some suggest that this therapy may slow the development of AAT deficiency in people who don't have severe disease.
People who have AAT deficiency and develop related liver or skin diseases will be referred to doctors who treat those diseases.
Researchers are working on possible treatments that will target the altered AAT genes and replace them with healthy genes. These treatments are in early stages of development.
If you're interested, talk to your doctor about whether any clinical trials of new AAT treatments might be right for you.
You can't prevent alpha-1 antitrypsin (AAT) deficiency, because the condition is inherited (passed from parents to children). If you inherit two altered AAT genes, you will have AAT deficiency. Even so, you may never have one of the diseases related to the condition.
You can take steps to prevent or delay the lung diseases linked to this condition.
If you have a lung disease related to AAT deficiency, you may want to discuss with your doctor the possibility of getting augmentation therapy. This is a treatment in which you receive infusions of AAT protein. This therapy raises the level of the AAT protein in your blood and lungs.
Living with AAT
People who have alpha-1 antitrypsin (AAT) deficiency don't always develop serious lung or liver diseases. This means that you can live with AAT deficiency and not even know you have it.
If you do know you have AAT deficiency, you probably also have a related lung or liver disease that requires ongoing medical care.
Some things you can do if you have AAT deficiency are:
If you feel depressed, scared, or upset after being diagnosed with AAT deficiency, talk to your doctor. He or she can recommend support groups or counseling to help you.