Alpha-1 antitrypsin deficiency (AATD) is an inherited condition that can cause lung and liver disease. In some people, the disease may shorten lifespan.
The severity of AATD varies greatly from person to person - even among those in the same family. Knowing which mutations a child inherits can serve as a guide to how severe his or her symptoms might be. Milder alleles, such as the common S allele, are primarily associated with adult-onset symptoms, if any.
As the name indicates, AATD is caused by a deficiency in a protein called alpha-1 antitrypsin. This protein protects the body from neutrophil elastase, an enzyme which normally fights infection in a helpful way. Without sufficient levels of alpha-1 antitrypsin, neutrophil elastase can attack and harm healthy tissue in the lungs. Abnormally formed alpha-1 antitrypsin can also accumulate in and damage the liver.
Ninety-five percent of AATD is caused by the presence of two Z alleles. People who inherit two copies of the Z allele ("ZZ") are most likely to have the severe symptoms of the disease, which are listed below. In addition, smokers with the disease are much more likely to develop symptoms than non-smokers. Secondhand smoke, particularly from one's parents, can also increase the chances of developing symptoms.
Emphysema, a chronic disease in which air sacs in the lungs lose their normal ability to expand and contract, is the most common symptom of AATD. Emphysema causes a progressive difficulty in breathing and a hacking cough. It can severely limit physical exertion. The first signs of emphysema, shortness of breath and wheezing, often appear between the ages of 40 and 50 in smokers with the disease. Non-smokers with AATD typically develop emphysema symptoms later, even after the age of 60.
Liver disease is another possible symptom of AATD. About 2% of children with AATD will develop severe liver complications. Common symptoms of these early liver problems include a swollen abdomen, swollen feet or legs, abnormal liver enzyme activity, and a yellowing of the skin or whites of the eyes (jaundice).
Overall, 15 to 19% of adults over the age of 50 with two Z alleles develop an accumulation of scar tissue in the liver (cirrhosis). This symptom can develop at any age, with greater risk of cirrhosis later in life. When liver disease associated with AATD begins later in life, destruction of the liver tissue can be rapid.
Higher risk for a particular type of liver cancer has been reported among people with AATD, notably in men.
Individuals with only one copy of the Z allele (called carriers) have a slightly elevated risk for lung or liver problems. One study placed this risk at 8%, versus 2 to 4% for the general population. Smokers who are carriers of the Z allele are more likely to develop lung problems, such as emphysema, while non-smoking carriers rarely do.Those who have one Z allele ("carriers") are more likely to have emphysema, particularly if they smoke.
In North America, AATD affects 1 in 5,000 to 7,000 people. In a study of 75,000 Europeans, researchers estimated that 1 in 4,700 were affected by AATD.
The Z allele is most common among individuals of Northwestern European, French Canadian, Cajun, Ashkenazi Jewish and Middle Eastern ancestry where up to 1 in 32 individuals are carriers.
AATD is rare in Asian and African populations, except in populations that are racially heterogeneous. For example, African-Americans in the United States have a higher rate of AATD than populations in Africa.
Researchers believe that AATD is often diagnosed as chronic obstructive pulmonary disease (COPD), a relatively common disease, without the realization that AATD is the cause of the COPD. For this reason, the disease may be more common than prevalence numbers indicate.
It is strongly recommended that all people with AATD avoid smoking. Smokers are more likely to develop symptoms of AATD. In smokers, symptoms tend to develop at an earlier age and progress at a faster rate. People with the disease should also avoid exposure to secondhand smoke, pollution, mineral dust, gas, and chemical fumes. Regular exercise and good nutrition are beneficial for people with AATD.
Carriers of the Z allele should likewise avoid smoking. While most carriers of the Z allele will never develop health problems related their carrier status, smoking does increase the chance that symptoms will arise.
Infusions of purified human alpha-1 antitrypsin have been recommended for some people with AATD. This treatment is considered most effective among people with moderate lung damage, though the overall effectiveness of this therapy has not been adequately studied.
In people with severe liver or lung disease, transplantation of the failing organ may be an option. However, lung transplants have not been shown to improve lifespan. Liver transplants can "cure" the disease because the donor liver will produce the alpha-1 antitrypsin protein.
The severity of symptoms associated with AATD varies widely, making the prognosis equally varied. In some people, the disease can shorten lifespan, while in others, it allows for a normal lifespan. Roughly 2% of children with two copies of the Z allele develop severe liver disease.
Overall, smokers show much more severe and rapid lung damage beginning earlier in life than non-smokers and those with one or more copies of the Z allele are more likely to develop symptoms. In non-smokers who develop lung complications after their 60th birthday, lifespan may be normal.
A non-profit advocating for all individuals affected by alpha-1 antitrypsin deficiency.
PO Box 202
103 Rapidan Church Lane
Wolftown VA 22748
Phone: (866) 367-2122
Secondary Phone: (540) 948-6777
A non-profit founded by individuals who have AATD, the organization is dedicated to providing the leadership and resources that will result in increased research and ultimately a cure for the disease. The organization also maintains a database of ongoing AATD research.
2937 SW 27th Avenue Suite 302
Miami FL 33133
Phone: (877) 228-7321
Secondary Phone: (305) 567-9888
Explanations of an extensive number of genetic diseases written for everyday people by the U.S. government's National Institutes of Health.