Alpha-1 antitrypsin deficiency (AATD) is an inherited condition that causes low levels of, or no, alpha-1 antitrypsin (AAT) in the blood. AATD occurs in approximately 1 in 2,500 individuals. This condition is found in all ethnic groups; however, it occurs most often in whites of European ancestry.
Alpha-1 antitrypsin (AAT) is a protein that is made in the liver. The liver releases this protein into the bloodstream. AAT protects the lungs so they can work normally. Without enough AAT, the lungs can be damaged, and this damage may make breathing difficult.
Everyone has two copies of the gene for AAT and receives one copy of the gene from each parent. Most people have two normal copies of the alpha-1 antitrypsin gene. Individuals with AATD have one normal copy and one damaged copy, or they have two damaged copies. Most individuals who have one normal gene can produce enough alpha-1 antitripsin to live healthy lives, especially if they do not smoke.
People who have two damaged copies of the gene are not able to produce enough alpha- 1 antitrypsin, which leads them to have more severe symptoms.
AATD can present as lung disease in adults and can be associated with liver disease in a small portion of affected children. In affected adults, the first symptoms of AATD are shortness of breath with mild activity, reduced ability to exercise and wheezing. These symptoms usually appear between the ages of 20 and 40. Other signs and symptoms can include repeated respiratory infections, fatigue, rapid heartbeat upon standing, vision problems and unintentional weight loss.
Some Individuals with AATD have advanced lung disease and have emphysema, in which the small air sacs (alveoli) in the lungs are damaged. Symptoms of emphysema include difficulty breathing, a hacking cough and a barrel-shaped chest. Smoking or exposure to tobacco smoke increases the appearance of symptoms and damage to the lungs. Other common diagnoses include COPD (chronic obstructive pulmonary disease), asthma, chronic bronchitis and bronchiectasis - a chronic inflammatory or degenerative condition of one or more bronchi or bronchioles.
Liver disease, called cirrhosis of the liver, is another symptom of AATD. It can be present in some affected children, about 10 percent, and has also been reported in 15 percent of adults with AATD. In its late stages signs and symptoms of liver disease can include a swollen abdomen, coughing up blood, swollen feet or legs, and yellowing of the skin and the whites of the eyes (jaundice).
Rarely, AATD can cause a skin condition known as panniculitis, which is characterized by hardened skin with painful lumps or patches. Panniculitis varies in severity and can occur at any age.
Alpha-1 antitrypsin deficiency (AATD) is diagnosed through testing of a blood sample, when a person is suspected of having AATD. For example, AATD may be suspected when a physical examination reveals a barrel-shaped chest, or, when listening to the chest with a stethoscope, wheezing, crackles or decreased breath sounds are heard.
Testing for AATD, using a blood sample from the individual, is simple, quick and highly accurate.. Three types of tests are usually done on the blood sample:
Individuals who have symptoms that suggest AATD or who have a family history of AATD should consider being tested.
Treatment of alpha-1 antitrypsin deficiency (AATD) is based on a person's symptoms. There is currently no cure. The major goal of AATD management is preventing or slowing the progression of lung disease.
Treatments include bronchodilators and prompt treatment with antibiotics for upper respiratory tract infections. Lung transplantation may be an option for those who develop end-stage lung disease. Quitting smoking, if a person with AATD smokes, is essential.
Replacement (augmentation) therapy with the missing AAT protein is available, although it is used only under special circumstances. It is not known how effective this is once disease has developed or which people would benefit most.
Alpha-1 antitrypsin deficiency is inherited in families in an autosomal codominant pattern. Codominant inheritance means that two different variants of the gene (alleles) may be expressed, and both versions contribute to the genetic trait.
The M gene is the most common allele of the alpha-1 gene. It produces normal levels of the alpha-1 antitrypsin protein.
The Z gene is the most common variant of the gene. It causes alpha-1 antitrypsin deficiency. The S allele is another, less common variant that causes ATTD.
If a person inherits one M gene and one Z gene or one S gene ('type PiMZ' or 'type PiMS'), that person is a carrier of the disorder. While such a person may not have normal levels of alpha-1 antitrypsin, there should be enough to protect the lungs. However, carriers with the MZ alleles have an increased risk for lung disease, particularly if they smoke.
A person who inherits the Z gene from each parent is called 'type PiZZ.' This person has very low alpha-1 antitrypsin levels, allowing elastase - an enzyme especially of pancreatic juice that digests elastin - to damage the lungs. A person who inherits an altered version called S and Z is also likely to develop AATD.
Currently, NHGRI is not conducting research on Alpha-1 Antitrypsin Deficiency.
Last Updated: January 4, 2012