Alpha-1 antitrypsin deficiency
What is alpha-1 antitrypsin deficiency?
Alpha-1 antitrypsin deficiency is an inherited disorder that can cause lung disease in adults and liver disease in adults and children.
The first signs and symptoms of lung disease caused by alpha-1 antitrypsin deficiency usually appear between the ages of 20 and 40 years. The earliest signs are shortness of breath following mild activity, reduced ability to exercise, and wheezing. Other signs and symptoms can include unintentional weight loss, recurring respiratory infections, fatigue, rapid heartbeat upon standing, and vision abnormalities. Advanced lung disease leads to emphysema, in which the small air sacs (alveoli) in the lungs are damaged. Characteristics features of emphysema include difficulty breathing, a hacking cough, and a barrel-shaped chest. Smoking or exposure to tobacco smoke accelerates the appearance of symptoms and damage to the lungs.
About 10 percent of infants and 15 percent of adults with alpha-1 antitrypsin deficiency have liver damage. Signs of liver disease can include a swollen abdomen, coughing up blood, swollen feet or legs, and yellowing of the skin and whites of the eyes (jaundice).
In rare cases, alpha-1 antitrypsin deficiency also causes a skin condition known as panniculitis, which is characterised by hardened skin with painful lumps or patches. Panniculitis varies in severity and can occur at any age.
How common is alpha-1 antitrypsin deficiency?
Worldwide, approximately 1 in 2,500 individuals has alpha-1 antitrypsin deficiency. This disorder is found in all ethnic groups, however, it occurs most frequently in whites of European ancestry.
What genes are related to alpha-1 antitrypsin deficiency?
Mutations in the SERPINA1 gene cause alpha-1 antitrypsin deficiency.
The SERPINA1 gene provides instructions for making a protein called alpha-1 antitrypsin. This protein protects the body from being damaged by a powerful enzyme called neutrophil elastase. Neutrophil elastase is released from white blood cells to fight infection, but it can attack normal tissues (such as the lungs) if not carefully controlled by alpha-1 antitrypsin. A mutation in the SERPINA1 gene can lead to a shortage (deficiency) of alpha-1 antitrypsin protein or an abnormal form of the protein that cannot control neutrophil elastase. Uncontrolled, neutrophil elastase destroys tiny air sacs in the lungs, which can lead to emphysema. The abnormal protein can also accumulate in the liver and may damage this organ.
How do people inherit alpha-1 antitrypsin deficiency?
This condition is inherited in an autosomal codominant pattern. Codominance means that two different versions of the gene may be expressed, and both versions contribute to the genetic trait.
The most common version (allele), called M, produces normal levels of the alpha-1 antitrypsin protein. Most people have two copies of the M allele (MM), one from each parent. Two altered versions that produce moderately low or very low levels of alpha-1 antitrypsin are called S and Z, respectively. Individuals with two copies of an altered allele (ZZ or SZ) are likely to develop alpha-1 antitrypsin deficiency.
Worldwide, about 116 million people carry a copy of the S or Z allele. Individuals with a MS or SS combination usually produce enough alpha-1 antitrypsin to protect the lungs. Carriers with the MZ alleles, however, may have an increased risk for lung disease, particularly if they smoke.
What other names do people use for alpha-1 antitrypsin deficiency?
* AAT
* alpha-1 proteinase inhibitor
* alpha-1 related emphysema
* genetic emphysema
* hereditary pulmonary emphysema
* inherited emphysema
