Alpha-1 antitrypsin deficiency is caused by an inherited gene mutation.
Infants may develop jaundice and liver damage.
Cirrhosis can develop during childhood.
Adults commonly develop emphysema, with shortness of breath, wheezing, and coughing, and some adults develop cirrhosis.
Tests that measure the amount of the enzyme in the blood and that detect the gene mutations are used for diagnosis.
People with emphysema take drugs to improve breathing and sometimes receive infusions of alpha-1 antitrypsin by vein.
Some people need lung or liver transplants.
Alpha-1 antitrypsin is an enzyme produced by the liver that inhibits the action of other enzymes called proteases. Proteases break down proteins as part of normal tissue repair. Alpha-1 antitrypsin protects the lungs from the damaging effects of proteases.
Alpha-1 antitrypsin deficiency results from an inherited mutation in the gene that controls production and release of the enzyme. There are many subtypes of alpha-1 antitrypsin deficiency, but in all, levels of active enzyme in the blood are insufficient, the enzyme is structurally abnormal (and thus functions poorly), or both. Whites are affected more often than Blacks or people of Asian or Hispanic ancestry.
The most common problems caused by the deficiency are
Liver damage
Emphysema (a form of chronic obstructive pulmonary disease Chronic Obstructive Pulmonary Disease (COPD) Chronic obstructive pulmonary disease is persistent narrowing (blocking, or obstruction) of the airways occurring with emphysema, chronic obstructive bronchitis, or both disorders. Cigarette... read more
, or COPD)
If the enzyme is structurally abnormal, it may clump in the liver, causing the liver to malfunction. In some people, liver malfunction leads to cirrhosis Cirrhosis of the Liver Cirrhosis is the widespread distortion of the liver's internal structure that occurs when a large amount of normal liver tissue is permanently replaced with nonfunctioning scar tissue. The scar... read more 
and to an increased risk of liver cancer.
The low levels of alpha-1 antitrypsin allow proteases to damage the lungs, resulting in emphysema Chronic Obstructive Pulmonary Disease (COPD) Chronic obstructive pulmonary disease is persistent narrowing (blocking, or obstruction) of the airways occurring with emphysema, chronic obstructive bronchitis, or both disorders. Cigarette... read more . Emphysema is more common (and worse) in people who smoke. Emphysema in nonsmokers can be caused by alpha-1 antitrypsin deficiency.
Disorders of other organs sometimes occur. These disorders include inflammation of fat under the skin (panniculitis), life-threatening bleeding, aneurysms, ulcerative colitis, vasculitis, and kidney disease.
Symptoms of Alpha-1 Antitrypsin Deficiency
Symptoms may first appear during infancy, childhood, or adulthood. About 10 to 20% of affected people have symptoms during infancy. Affected infants develop yellowing of the skin and the whites of the eyes (jaundice Jaundice in Adults In jaundice, the skin and whites of the eyes look yellow. Jaundice occurs when there is too much bilirubin (a yellow pigment) in the blood—a condition called hyperbilirubinemia. (See also Overview... read more 
) and an enlarged liver during the first week of life. Jaundice disappears at about age 2 to 4 months. However, about 20% of these infants later develop cirrhosis, and some die before reaching adulthood.
Adults commonly develop emphysema, with progressively increasing shortness of breath, difficulty breathing, coughing, and wheezing. Emphysema rarely develops before age 25. It develops earlier and is more severe in smokers than in nonsmokers. The severity of symptoms also varies depending on the form of the deficiency, other disorders people have, environmental exposure to lung irritants, and other factors. If people have never smoked, their symptoms tend to be moderate, and most have a normal life expectancy.
Even if they did not have liver problems during infancy, about 10% of adults develop cirrhosis, which may eventually lead to liver cancer.
People with panniculitis have painful, tender bumps or discolored patches on the lower abdomen, buttocks, and thighs. The bumps may feel hard to the touch.
Diagnosis of Alpha-1 Antitrypsin Deficiency
Alpha-1 antitrypsin deficiency is suspected in the following:
Infants who have typical symptoms
Smokers who develop emphysema before age 45
Nonsmokers who develop emphysema at any age
People with an unexplained liver disorder
People who develop panniculitis
People with a family history of emphysema or unexplained cirrhosis
People with a family history of alpha-1 antitrypsin deficiency
Because the deficiency is inherited, doctors usually ask whether any family members have had emphysema or cirrhosis with no known cause.
The deficiency is usually confirmed by genetic testing, which also can determine the specific form of the deficiency. Doctors also usually do blood tests to measure the level of alpha-1 antitrypsin.
Treatment of Alpha-1 Antitrypsin Deficiency
Emphysema
People who smoke are advised to stop Smoking Cessation Most people who smoke want to quit and have tried doing so with limited success. Effective tools to help quit smoking include counseling, nicotine replacement products, and medications. While... read more . Bronchodilators, drugs that relax the muscles around the small airways and thus widen the airways, such as albuterol may help ease breathing and relieve cough. Lung infections that develop are treated promptly.
Alpha-1 antitrypsin may be given by vein to replace the deficient enzyme. It is collected from a group of donors and screened for bloodborne disorders. Thus, it is expensive and is most beneficial to people who have only moderate symptoms due to emphysema and do not smoke. This treatment is thought to prevent further damage but does not reverse damage already done.
If people are younger than 60 and have severe symptoms, lung transplantation Lung and Heart-Lung Transplantation Lung transplantation is the surgical removal of a healthy lung or part of a lung from a living person and then its transfer into someone whose lungs no longer function. Heart-lung transplantation... read more may be done. A few medical centers sometimes do transplantations in highly selected people as old as 70. A few medical centers also sometimes do lung volume reduction surgery Other treatments .
Liver damage
Taking alpha-1 antitrypsin does not treat or prevent liver damage because liver damage is caused by production of an abnormal enzyme, not by enzyme deficiency. If the liver is severely damaged, liver transplantation Liver Transplantation Liver transplantation is the surgical removal of a healthy liver or sometimes a part of a liver from a living person and then its transfer into a person whose liver no longer functions. (See... read more may be done. The transplanted liver does not become damaged because the alpha-1 antitrypsin it produces is normal and thus does not accumulate in the liver.
Panniculitis
Doctors may give corticosteroids, antimalarial drugs, or certain antibiotics (tetracyclines) to relieve inflammation. But whether these drugs are effective is unclear.
Drugs Mentioned In This Article
| Generic Name | Select Brand Names |
|---|---|
albuterol |
Accuneb, ProAir digihaler, Proair HFA, ProAir RespiClick, Proventil, Proventil HFA, Proventil Repetabs, Respirol , Ventolin, Ventolin HFA, Ventolin Syrup, Volmax, VoSpire ER |
