Alpha-1 Antitrypsin Deficiency (AATD)

Alpha-1 antitrypsin deficiency (AATD) is a common, serious disease that is passed down from parents to children. It can cause liver and lung disease. The liver makes a protein called alpha-1 antitrypsin that goes into the bloodstream. This protein protects the lungs and allows them to work normally. If there is not enough alpha-1 antitrypsin, it is called alpha-1 antitrypsin deficiency (AATD).

Alpha-1 antitrypsin deficiency is the most common genetic cause of liver disease in children and is the most common genetic disease for which liver transplantation is done.

Some studies suggest one in 3,000 Americans have AATD, and that 95 percent of these individuals have not been diagnosed.

Alpha-1 antitrypsin is a protein that is made in the liver and then released into the bloodstream. Sometimes a gene mutation produces an abnormal form of this protein which cannot be released from the liver, which means it cannot enter the bloodstream.

Alpha-1 antitrypsin's job is to protect tissues in the body from being digested by enzymes released from inflammatory cells. Enzymes may then attack the lung and / or liver tissue.

In very young children, alpha-1 antitrypsin then accumulates in the liver, causing damage to the liver. Approximately 10 percent of infants born with the severe deficiency have liver disease that is fatal without a liver transplant.

Alpha-1-antitrypsin deficiency is an inherited condition and does not appear unless a person receives the same defective gene from both parents. If both parents carry an abnormal gene for alpha-1 antitrypsin deficiency disease there is: 

  • A 25 percent chance their child will develop the disorder 
  • A 50 percent chance their child will receive one defective gene from one of the parents, which means the child will not show symptoms of the disorder but is a "carrier" 
  • A 25 percent chance their child will receive both normal genes, one from each parent, and will be unaffected

Jaundice that doesn't clear up may be the first sign of an 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 
  • Ascites (the accumulation of a watery fluid that is produced by membranes when they are inflamed in the tissue that lines the belly) 
  • Feeding difficulties 
  • Poor growth or failure to thrive

Other children may not show signs of this condition until early childhood. First signs may include: 

  • Elevated liver enzyme levels 
  • Easily tired 
  • Loss of appetite 
  • Swelling of the legs or belly 
  • Enlargement or inflammation of the liver 
  • Jaundice, fever 
  • Enlarged spleen 
  • Ascites (the accumulation of a watery fluid that is produced by membranes when they are inflamed in the tissue that lines the belly) 
  • Pruritus (severe itching of the skin) 
  • Panniculitis (rare form of skin disease that is an inflammation of fat just beneath the skin, causing the skin to harden and form lumps)

Alpha-1 antitrypsin deficiency uses a simple blood test that measures the type of alpha-1 antitrypsin circulating in the blood. This test can tell whether a person is deficient or is a carrier. The blood test can be done soon after a baby is born if it is known that members of the baby's family carry the alpha-1 antitrypsin deficiency gene. A test also is available to check if a baby in the womb has the condition.

Liver disease resulting from alpha-1 antitrypsin deficiency can be determined by abnormal changes found in blood, urine and liver function tests. A doctor can tell by feel during a physical exam if something is not normal. A CT scan, and ultrasound and radioisotope scans of the liver and spleen also can detect damage. A liver biopsy can confirm the diagnosis.

If bilirubin (a liquid produced in the liver that removes toxins from the body and helps break down fat in food) levels are higher than normal, it may be a sign of alpha-1 antitrypsin deficiency. Increased levels of certain enzymes and abnormal ratios of certain proteins may also indicate liver disease.

Alpha-1 antitrypsin deficiency affects children differently. One child may not show any signs of liver disease and another child may be seriously affected. Only a small percentage of children develop liver disease because of the deficiency.

There is no cure for alpha-1 antitrypsin deficiency. If liver disease has developed, a liver transplant is currently the only option available for survival. The goal of treatment is to relieve the symptoms. 

  • Medicine may be given for severe itching or jaundice. 
  • Diuretics may be used to help reduce body fluid buildup. 
  • A healthy diet and vitamin supplements can provide essential nutrients and may increase overall quality of daily living. Eating a number of smaller meals during the day keeps the digestive process from interfering with breathing. 
  • Vitamin / nutrition supplements may increase the effectiveness of the digestive process and increase energy levels. 
  • Shunts (a kind of bypass) may be surgically inserted to lower the pressure within the blood vessels in the liver for people with liver disease caused by alpha-1 antitrypsin deficiency.

Transplantation can result in a cure of alpha-1 antitrypsin deficiency. If a transplant is the best treatment option, the doctor and the other members of the patient care team focus on preventing complications. They will treat symptoms while your child waits for a donated liver. A liver transplant totally replaces the abnormal liver cells that produce the abnormal alpha-1 antitrypsin deficiency and corrects the protein abnormality.

It is critical for a child with AATD to avoid smoking or being exposed to second-hand smoke.

There is good chance of avoiding liver disease since only about 10 percent of children with alpha- 1-antitrypsin deficiency develop significant liver disease. Liver transplants have been effective in reversing the symptoms of liver failure due to alpha-1 antitrypsin deficiency.

Last Updated 10/2012