Alpha-1-antitrypsin deficiency (A1AT) is a genetic disease that causes liver disease in children.  It is perhaps better known for it's ability to cause lung disease in adults.  A1AT is a chemical that is normally produced by the body in the liver.  This chemical travels through the bloodstream and blocks the effects of excess neutrophil proteases (chemicals which destroy proteins).  The effect of low levels of A1AT in adults is damage to the lungs.  These adults can develop life-threatening lung disease at a relatively young age.  A1AT lung disease is similar to emphysema (a disease that most often affects the elderly).  The genetic defect causes abnormal A1AT to collect in liver cells instead of being released into the blood.  The high levels of A1AT in liver cells can cause hepatitis (inflammation in the liver) and even liver failure in some children.  Many children with A1AT deficiency do not develop liver disease, and it is difficult to predict which children will develop liver damage.  Some children with A1AT liver disease develop jaundice (yellow skin color) as newborn infants, and some children show signs of liver disfunction as a toddler or school-age child.  There is no treatment for A1AT liver disease (or lung disease for that matter) at this time.  Some children who develop liver failure will require a liver transplant.  Possible future non-surgical therapies are being developed.

What is alpha-1-antitrypsin deficiency (A1AT)?

A1AT is a chemical normally produced in the liver.  When working properly, this chemical travels through the blood to inhibit the effects of excess protein-destroying chemicals produced by white blood cells.  The body maintains an efficient balance between the chemicals used by white blood cells to fight infection and chemicals used to control these effects.  People born with the gene defect associated with A1AT deficiency produce abnormal A1AT that gets stuck in liver cells.  This causes two problems: 1. Excess abnormal A1AT damages liver cells and causes inflammation in the liver of children.  2. The lack of normal A1AT in the blood leads to lung damage in adults.

How common is A1AT deficiency in children?

A1AT deficiency is the most common genetic cause of liver disease in children.  In the United States, approximately 1 out of 2000 children have the disorder.  About 15 out of 1000 people in the United States have the gene (they are "carriers" but do not have the disorder).  An estimated 70,000 people in North America have an abnormal A1AT gene.  The gene and disorder is most common in caucasians in North America, Australia, and Europe.

How many children with an abnormal A1AT gene will develop liver disease?

Only about 10% of children with an abnormal A1AT gene will develop liver disease.  This probably means that there are other unknown factors that lead to the development of disease.

What are the symptoms of A1AT deficiency in kids?

Most children with an abnormal A1AT gene have NO symptoms.  Approximately 10% of affected children will develop signs of liver disease.

• Persistent jaundice (the direct bilirubin blood test is abnormal - most infants with jaundice have an elevated indirect bilirubin level)
• Hepatomegaly (a big liver)
• Splenomegaly (a big spleen)
• Liver dysfunction or failure

What tests are available for A1AT deficiency?

Blood tests

• Indirect and direct bilirubin
• Liver function tests
• Serum level of alpha-1-antitrypsin
• Protein electrophoresis (called a Pi test - this is the best test)

Imaging

• Ultrasound or computed tomography (CT) may be used to determine effects on the liver

Liver biopsy

• May be used to determine the extent of liver damage (i.e., fibrosis or cirrhosis)

What is the treatment for A1AT liver disease?

• Unfortunately there is no specific medicine for A1AT liver disease.
• Ursodeoxycholic acid is a medicine that helps improve the flow of bile through the liver.
• Trials of alpha-1-antitrypsin replacement are underway, although this type of therapy only treats lung disease and not liver disease.
• Routine vaccinations and influenza shots should be given.
• Liver transplantation is reserved for children with liver failure.

Photo credit: Christaras A, 8 October 2006.  Abdominal computed tomography of a 3 year old child showing liver cirrhosis in transverse section.

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