Alpha-1 antitrypsin deficiency Dr Trisha Macnair This hereditary condition can cause emphysema, liver disease and lung infections, so is important to diagnose early.

In this article

What is alpha-1 antitrypsin deficiency? Symptoms

Causes and risk factors Treatment and recovery

Alpha-1 antitrypsin deficiency (A1AD or AAT deficiency) is an inherited condition where a person lacks a protein known as alpha-1 antitrypsin, made by the liver. There may be low levels of the protein but it doesn't work properly.

Alpha-1 antitrypsin (AAT) is particularly important in the lungs, where it mops up another enzyme called neutrophil elastase. This enzyme normally digests damaged or ageing lung cells, foreign particles and bacteria, but has the potential to harm healthy lung tissue.

In AAT deficiency, neutrophil elastase cannot be neutralised efficiently, so it's able to destroy healthy tissue. The common result is emphysema of the lungs. It's thought that abnormal AAT also collects in the liver and can contribute to liver cirrhosis, although many people with AAT deficiency don't develop liver disease.

Although AAT deficiency is present from birth, the effects often don't become apparent until someone is over 50 years old.

The most common effect is emphysema. The air sacs (alveoli), which transfer oxygen from the air into the blood, become damaged. As a result the alveoli lose their elasticity, leaving them overinflated and unable to expand and contract as normal. Holes also develop in their stretched walls, making them less able to fill with enough air and consequently even less effective.

People with emphysema experience coughing, shortness of breath (often on minimal exertion) and wheezing. They're often believed to be suffering from asthma before the necessary blood test is performed that shows a lack of AAT enzyme.

Liver problems may be apparent from birth or show up later in adult life. A newborn baby may show non-specific signs of liver disease such as jaundice, pale stools, excessive bleeding or an enlarged liver. This is called 'neonatal hepatitis syndrome' and usually begins between four days and six weeks after birth. Most babies will get better, although some rapidly develop liver failure. Others develop chronic liver disease, either in childhood or as an adult. Occasionally in severe cases, complications such as bleeding from the gut, drowsiness or coma can occur.

In the liver, damaged liver cells become scarred and fibrosed as a result of inflammation. This damage, known as cirrhosis, is irreversible and leaves the liver functioning poorly. Loss of weight, abdominal fluid collection (ascites), jaundice and easy bleeding may all result from this liver damage.

To protect the liver from further unnecessary damage, people with AAT deficiency are advised to avoid alcohol and, if possible, medicines that may harm the liver. It's also important to eat a healthy diet packed with fresh fruit and vegetables.

AAT deficiency is one of the most common genetic disorders, found throughout the world but more common in some countries than others. In each of our cells we have two copies of the gene that controls AAT production. In order to be affected by AAT deficiency, a person must inherit a faulty gene from each of their parents. This is called autosomal recessive inheritance.

However, it is now known that there are a large number of different variations in the gene for AAT, which means that there are many variations of the condition. Carrying just one faulty copy of the gene can cause lower levels of AAT to be produced, and in some cases, increase the risk of lung disease later in life.

In a recent survey of 58 countries with a total population of 4.4 billion, there were at least 116 million people carrying one gene for AAT deficiency, and 3.4 million with combinations of faulty genes. Some combinations produce no apparent symptoms while others lead to severe disease. It’s likely that most cases of AAT deficiency are so mild that they are never diagnosed.

Relatives of those with the deficiency are offered screening to establish whether they're carriers. If the abnormal gene is identified, couples who want to start a family are offered genetic counselling.

The outlook for most people with AAT deficiency is good – many won’t even know they have the condition while others can keep healthy with careful management. Although progressive liver or lung disease affects only a minority, it can be serious, so regular monitoring of those with the condition is important.

There's no specific treatment or cure for AAT deficiency, but some doctors are testing whether giving patients regular (usually weekly) injections of replacement AAT enzyme may be of benefit. This replacement enzyme, which is extracted from human blood, is used routinely in some countries but not as yet in the UK.

People with AAD deficiency are especially vulnerable to exposure to chemical and particulate environmental pollutants, which can aggravate both lung and liver disease. For this reason the most important thing someone with AAT deficiency can do for their health is not to smoke and to avoid people who smoke around them. They are also very susceptible to recurrent lung infections, so it's particularly important they receive immunisation against pneumococcal and flu infections.

Exercise will boost the immune system to protect the body from infection and is also essential. Medicines to improve lung function and oxygen therapy are also regularly used if lung damage and emphysema have developed.

As with severe liver disease, when lung damage is severe an organ transplant may be considered.

This article was last medically reviewed by Dr Trisha Macnair in February 2009.