Alpha-1 Antitrypsin Deficiency

Alpha-1 antitrypsin (AAT) deficiency is an inherited (genetic) disease. In patients with the disease, their liver does not release enough AAT protein into the bloodstream.

The disease is quite common, with 1 person affected in every 1,500 to 2,500 people. AAT deficiency is caused by changes (called variants) in a gene called SERPINA1. These gene changes can result in a defective AAT protein that gets trapped in the liver cells. The defective AAT protein in the liver may cause liver inflammation (called hepatitis) that can eventually cause permanent liver scarring (called cirrhosis) and liver failure.

In addition to liver inflammation or damage, patients with AAT deficiency may develop lung disease. This happens because the AAT protein normally protects the lungs. In patients with AAT deficiency, AAT is stuck in the liver and cannot protect the lungs. Without AAT, the lungs can be damaged by inflammation, leading to emphysema.

Testing for AAT deficiency is usually done when a child has abnormal liver tests, or when a family history suggests a child may be at risk for AAT deficiency. Your doctor may first measure the amount of AAT protein in your child’s blood. In cases of AAT deficiency, the blood AAT level will be low.

An additional blood test is done to look for the specific type of SERPINA1 gene variants (called alleles). Each individual has two alleles of SERPINA1. Most individuals with normal AAT levels have either one or two “M” alleles, with M considered to be the “normal” allele. Patients who have either a “Z” or “S” allele have SERPINA1 variants that put them at risk for AAT deficiency. If a person has one M (normal protein) and one Z allele (abnormal protein), they usually have no medical issues. However, a person who inherits two disease-causing alleles (Z and Z; or S and Z) is at risk for liver and lung disease. Other combinations of variants may cause low AAT levels that do not lead to liver disease.

There is no medication to treat liver disease caused by AAT deficiency. To protect their vulnerable lungs, it is very important that individuals with AAT deficiency and those around them do not smoke tobacco or other substances (including e-cigs/vaping).

Individuals with AAT deficiency will undergo routine monitoring of their liver enzymes and of their liver by imaging (ultrasound) to check their liver function and health. A child with AAT deficiency should be vaccinated to protect against viruses that can further damage the liver, such as Hepatitis A and Hepatitis B.

It is difficult to predict how severely a liver will be affected by AAT deficiency. Some patients may have minimal liver disease during their entire lifetime. A small number of patients will eventually require liver transplantation due to severe liver damage that leads to liver failure. The genetic defect is cured with the new liver, so the liver disease will not return and lung disease will not progress.

A recently developed enzyme replacement therapy can prevent the progression of lung disease in patients with AAT deficiency.

Authors: Mercedes Martinez, MD and Amber Hildreth, DO
Editor: Athos Bousvaros, MD
September 2021