What is Alpha-1-Antitrypsin Deficiency?
Alpha-1-antitrypsin (A1AT) deficiency is an inherited disease in which a protein known as A1AT is unable to be released from the liver into the blood in adequate amounts. This causes a deficiency of the A1AT protein in the circulation. A1AT is a specialized protein that blocks the action of other proteins important in inflammation (swelling) and breakdown of tissues in the body. When the A1AT protein is deficient in the circulation, tissue inflammation and tissue damage is more severe, especially in the lungs. The defective A1AT protein that remains in the liver may cause liver inflammation (hepatitis) that can progress to cirrhosis (permanent liver scarring) and liver failure.
A1AT deficiency is quite common, with about 1 in 1,500 to 2,000 people affected. Both parents must be "carriers" of the genetic defect to have a child with A1AT deficiency. Although “carrier” parents partially produce the abnormal A1AT protein, they usually have no, or very minimal symptoms and they may not realize they are partially affected until their child is diagnosed with the condition.
About 10 percent of newborns with liver disease will be diagnosed with A1AT deficiency. Newborns may develop jaundice as part of inflammation of the liver associated with A1AT deficiency. Older children and teens can present with a liver that has been inflamed for a long time, causing scarring (cirrhosis) to develop. Lung disease usually develops only in adulthood. Adults with A1AT deficiency may have difficulties with COPD (chronic obstructive pulmonary disease), emphysema, chronic bronchitis, asthma, coughing, and repeated lung infections.
Testing is usually done when a child has liver inflammation of uncertain cause, or when a family history suggests A1AT liver disease. The standard screening test is to measure the amount of A1AT protein in the circulation. In cases of A1AT deficiency, the serum A1AT level will be low. When a low A1AT level is found, an additional test is usually done to identify the types of abnormal A1AT proteins that are in the circulation. In rare cases, a more detailed analysis of the DNA in the gene may be necessary.
The amount of liver swelling and damage can be assessed by ultrasonography of the abdomen (sonogram); blood tests of liver inflammation and function; and a liver biopsy where a small piece of liver tissue is obtained and then examined under the microscope to search for changes typical of A1AT deficiency.
There is no cure for A1AT deficiency. Therapy involves controlling symptoms and attempting to prevent the development of complications. It is very important for the affected person and those around him/her never to smoke in order to protect their lungs. Vaccinations to protect against viruses that can further damage the liver, such as Hepatitis A and Hepatitis B, should be given. It is difficult to predict how severely a liver will be affected. Liver function tests are followed over time. Some patients may have minimal liver disease during their entire lifetime; however a small number will eventually require a liver transplant.
Alpha-1-antitrypsin (A1AT) deficiency is treated in the Pediatric Liver Center at Hopkins Children's.