Alpha-1-antitrypsin deficiency (AATD)

This information is for people in the UK who have been diagnosed with alpha-1-antitrypsin deficiency (AATD, also called A1ATD), their families, friends and carers.

It aims to explain what AATD is and what causes it, as well as what the symptoms are, how it is diagnosed and options for treatment.

What is alpha-1-antitrypsin?

Alpha-1-antitrypsin (AAT) is a protein mainly produced by your liver that is released into in your blood. There are other proteins called enzymes that are found in all parts of your body that help to make sure that chemical reactions in your body take place normally. Enzymes have many important roles in your lung, including removing bacteria and fighting infections. The AAT protein is needed to control enzyme activity to prevent healthy lung tissue being damaged.

What is severe alpha-1-antitrypsin deficiency?

AATD is a rare, inherited condition that affects around one in 3,000 to one in 4,000 people in the UK. The most common reason for severe deficiency is if you carry an abnormal gene known as Z-AT, which affects the level of your AAT protein.

To inherit AATD, a Z-AT gene must be passed on by both of your parents. If you carry two Z-AT genes, your AAT level will be only 10-20 per cent of what it should be.

The AAT protein affected by the Z-AT gene builds up in the liver. This means you don’t have enough AAT to control the enzymes in your body, so healthy lung tissue can be damaged. This can cause emphysema, especially if you smoke.  Emphysema is one of the lung conditions known as chronic obstructive pulmonary disease (COPD).

There are other types of genes that also cause low levels of AAT, but only some cause severe deficiency. If you carry just one abnormal Z-AT gene, this will not cause the condition as the level of AAT in your blood is enough to control the enzymes.

What are the symptoms of alpha-1-antitrypsin deficiency?

People are born with AATD, but lung symptoms don’t usually start before the age of 20. More commonly, symptoms start after the age of 40.

If you have AATD, you can develop COPD early in your life and it might progress more rapidly than usual, especially if you smoke. People with AATD who smoke might develop COPD symptoms in their 20s, while people with AATD who have never smoked are more likely to have symptoms over the age of 40. Without AATD, COPD symptoms don’t normally develop until you are over 50.

The symptoms of AATD are due to the development of COPD. They include:

  • breathlessness during exercise or physical activity
  • wheezing
  • cough

Not everyone with AATD will get COPD. There are many genetic variations and only people with the lowest levels of AAT in their blood are likely to develop COPD. At present it is not known how many people with AATD will develop COPD, but some people will remain well.

Liver

About one in ten children who have AATD might have problems with their liver. AATD might also be associated with yellowing of the skin and eyes, called jaundice, in new-born babies. Although most people with AATD develop some liver scarring, only a small number of people develop symptoms of liver disease. Most people remain healthy.

How is alpha-1-antitrypsin deficiency diagnosed?

AATD can be confused with asthma. If you are under the age of 40 and have any of the symptoms mentioned above, you should ask your doctor to do some tests to see if you have AATD. You should also request tests if you have a family member who has been diagnosed with AATD.

You might need to have a blood test to measure the levels of AAT in your blood. If the level is low, you might need to have more tests to find out what type of deficiency you have and how severe it is and you might be assessed by a specialist in AATD.

If you are diagnosed with AATD, your family members, especially brothers and sisters, should be tested to see if they have the condition as well.

Can I be treated for alpha-1-antitrypsin deficiency?

There is no specific approved treatment in the UK yet for AATD. However, if you smoke, it is essential that you stop in order to slow down the development of COPD. You should also avoid being regularly exposed to irritants such as dust and gas in your job that might encourage COPD to develop faster.

If you have COPD caused by AATD, this can be treated in the same way as COPD that is not caused by AATD. For example, your doctor might prescribe an inhaler to help with feeling out of breath. Or you might be referred to pulmonary rehabilitation, a programme of exercise and education for people with a long-term lung condition. It combines physical exercise sessions with discussion and advice on your lung health and is designed to help you manage the symptoms of your condition, including feeling out of breath.

You might be suitable for a lung transplant if you have severe lung disease. However, because of a shortage of suitable organ donors and the significant risk of the operation, transplants are only considered in very unusual circumstances.

Other tips

  • If you have COPD caused by AATD, leading a healthy lifestyle is important to help you manage your symptoms. This includes eating a balanced diet, managing your weight and getting regular exercise.
  • Make sure you get a flu jab every year to help you avoid chest infections and stay away from friends or family when they have infections. In people with COPD and AATD, chest infections lead to a quicker decline in your lung function. If you have a cough that produces green mucus or phlegm you should see your doctor as you might have an infection and need a course of antibiotics.
  • Ask your doctor about getting vaccinated against pneumonia.

Possible future treatments

Augmentation therapy is a treatment where AAT is given into your veins to increase the levels of AAT in your body. It aims to try to slow down the progression of COPD caused by AATD. It is available in many countries, but not currently in the UK.

A recent review of the two clinical trials performed so far concluded that there was no medical benefit from the drug and that it could not be recommended. However, this review has received some criticism, and some researchers suggest that the treatment might benefit some people with AATD.

Augmentation therapy is currently being looked at in more detail and a new trial has been completed. Early findings are promising, but we still don’t know the final conclusion of the trial.

Research is also looking at ways to correct the gene that leads to low levels of AAT, to stop AAT collecting in the liver and to promote the release of AAT into the blood.

Lung volume reduction has not been looked at in great detail in AATD, but some data suggests that lung volume reduction might have some short-term benefits.

Alpha-1 UK support groups

Support groups for people with A1AD, their families and carers.


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Information Standard logoLast medically reviewed: September 2014. Due for review: September 2016.

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