Alpha-1 antitrypsin is a protein made by the liver that helps block the actions of bad proteins related to inflammation and breakdown of tissues. When the liver does not make enough alpha-1 antitrypsin, other organs can be damaged, especially the lungs. Most people with alpha-1 antitrypsin deficiency don't know they have it and never develop liver disease. Defective alpha-1 antitrypsin that remains in the liver can cause jaundice (yellowing of the skin) in infants, cirrhosis (scarring of the liver), portal hypertension (an increase in pressure within the portal vein, which carries blood from the digestive organs to the liver) and potentially liver failure later in life. The jaundice in infants with alpha-1 antitrypsin usually resolves in the first year of life. Less than half of those children will develop chronic liver disease later. Sometimes older children or adults with a new diagnosis of cirrhosis and portal hypertension are found to have alpha-1 antitrypsin deficiency. Adults with the disease will likely develop chronic obstructive pulmonary disease, emphysema, bronchitis, asthma, coughing and repeated lung infections, particularly if they are exposed to cigarette smoke.

Causes

Alpha-1 antitrypsin deficiency is a genetic disease. This means that it is transmitted through an abnormal gene passed from parent to child. It is an autosomal recessive gene, which means that if the mom and the dad both carry the gene, 1 out of 4 of their children will inherit both abnormal copies of the gene, producing a child who has alpha-1 antitrypsin deficiency.

Not everyone with alpha-1 antitrypsin deficiency develops liver disease. A large study in Sweden revealed that only 15% of people who have the disease actually develop obvious liver disease. The same abnormality in the other 85% of people causes no obvious disease. Researchers are actively investigating why some patients with alpha-1 antitrypsin deficiency may develop progressive liver disease while others are essentially normal. It seems that a second abnormality in liver cells in addition to the abnormal protein may stimulate the progression of liver disease.

Symptoms

Jaundice that doesn't clear up may be the first sign of alpha-1 antitrypsin deficiency in an infant. Other symptoms in infancy may include:

• Elevated liver enzyme levels
• Dark urine, pale stools
• Itching
• Enlarged liver
• Bleeding
• Feeding difficulties
• Poor growth or failure to thrive

Exams and Tests

Your pediatric GI specialist can diagnose alpha-1 antitrypsin deficiency with simple blood test. Other testing may include routine biochemical tests of liver function, ultrasound imaging or liver biopsy.

Ultrasound

Your child's pediatric gastroenterologist may also order an ultrasound test to assess damage to the liver. This may be done periodically to detect changes in the liver.

Liver Biopsy

Your child's pediatric gastroenterologist will perform a liver biopsy to look for inflammation and scarring inside the liver. Your child will receive sedation medications or a general anesthetic before the biopsy. These medications will prevent your child from feeling pain or anxiety or remembering the procedure. An area on the right side of your child's abdomen or mid-upper abdomen will be cleansed with an antibacterial soap. The biopsy site will then be numbed with an injection of lidocaine (numbing medicine). The doctor will insert a needle through the skin and into the liver to obtain a very small piece of liver tissue. The sample will be sent to a lab and analyzed. The doctor will apply a small pressure dressing (bandage) to the site.

After the biopsy your child will stay in or return to his/her room for four hours, when a repeat blood count is checked. (Children less than one year are observed overnight.) He or she should lie on the right side or back, depending on the biopsy site, for two hours. Being in bed will reduce the chance of bleeding after the biopsy. Once your child is awake and alert, he/she will be allowed to drink fluids. If fluids are tolerated, a regular diet can be restarted. For the remainder of the day, your child will need to participate in quiet activity. The results of the liver biopsy are usually available two weeks after the procedure.

Treatment

There is no treatment for alpha-1 antitrypsin deficiency other than treatment of related symptoms. Scientists are actively working to discover a treatment for this liver disease.

While your baby is jaundiced and the liver not working normally, nutritional support and supplementation of fat-soluble vitamins, especially vitamins E, D and K, are very important. Once the jaundice resolves your child should be followed at regular intervals to monitor the development of progressive liver disease. Half of previously jaundiced babies will have no later evidence of liver disease.

Children with alpha-1 antitrypsin deficiency often have an enlarged liver. If scarring of the liver progresses, enlargement of the spleen may also be seen. Blood tests are used to detect elevated liver enzymes and assess liver function. In the event of severe liver disease due to alpha-1 antitrypsin deficiency, liver transplantation can be done with excellent success.

Points to Remember

• Children born with alpha-1 antitrypsin deficiency often experience jaundice at birth but may not have any other symptoms.
• Nutritional supplementation is important.
• Children can live a fairly normal life.
• Lung problems usually develop in adulthood.

For More Information

Alpha-1 Foundation - alphaone.org

American Liver Foundation - liverfoundation.org

North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition - NASPGHAN.org

The Childhood Liver Disease and Education Network - childrennetwork.org