Alpha-1 antitrypsin deficiency: symptoms, causes, diagnosis and treatment

Alpha-1 antitrypsin deficiency (AATD) is a genetic inherited condition. Asthma + Lung UK says that people with AATD lack a protective chemical in the body called alpha-1-antitrypsin, and that low levels increase the risk of lung diseases like chronic obstructive pulmonary disease (COPD) and in some cases bronchiectasis.

Alpha-1 UK, a support group founded by people diagnosed with the condition, explains that alpha-1 antitrypsin (AAT) is an enzyme produced in the liver to help protect the tissues of the body during infections. The AAT is abnormal and cannot be released from the liver at the normal rate, which leads to a build-up of abnormal AAT in the liver that can cause liver disease, and a decrease of AAT in the blood that can lead to lung disease.

Around 1 in 3000 people in the UK have AATD, according to Asthma + Lung UK.

Asthma + Lung UK says AATD does not directly cause symptoms in the lungs, but it increases the risk of lung disease in adults. The first symptoms you might notice are shortness of breath, coughing, wheezing, feeling tired and chest infections that keep coming back. Some people with AATD do not get any symptoms.

Liver symptoms are more likely to happen in children, but adults can also develop liver disease called cirrhosis, which is scarring of the liver. The NHS says many people with cirrhosis do not have symptoms, especially early on. Early symptoms may include feeling tired or unwell all the time, loss of appetite or weight loss, feeling or being sick and tummy pain.

Rare complications include panniculitis, a skin condition that forms painful red lumps which can become ulcers, and, in rare cases, vasculitis, which is inflammation in the blood vessels affecting the kidneys.

• Shortness of breath, coughing, wheezing and tiredness.

• Chest infections that keep coming back.

• Liver disease, more likely in children, with cirrhosis possible in adults.

• Painful red skin lumps (panniculitis) in rare cases.

Asthma + Lung UK says AATD is caused by one or more genes not working properly. You get a copy of the alpha-1 antitrypsin (AAT) gene from each parent. With one damaged copy, you should be able to produce enough AAT to live a healthy life, especially if you do not smoke. With two damaged copies, you may not be able to produce enough, which means the lungs can become easily damaged.

Because it is inherited, you are more likely to have it if a family member has it. Asthma + Lung UK says that if a family member, particularly a parent, brother or sister, has been diagnosed, you should get tested.

With a low level of AAT, the lungs are not as protected as they should be from infections, cigarette smoke and other toxins, so they become easily damaged. Asthma + Lung UK says that if you have AATD, COPD can sometimes occur at a younger age and may progress quicker than normal, especially if you smoke.

The NHS describes COPD as a group of lung conditions that cause breathing difficulties, including emphysema and chronic bronchitis. It says the main cause is smoking, but that some cases are the result of a rare genetic problem that makes the lungs more vulnerable to damage.

AATD is diagnosed by a blood test that measures the level of AAT. Asthma + Lung UK says your doctor might decide to test for AATD if you have developed COPD at a young age, have a family history of AATD, or have symptoms of liver disease, particularly in children born with jaundice.

It says that if you are diagnosed with COPD and are under the age of 45 you should ask your doctor to test you for AATD, and that you should also be tested if you have COPD but have never smoked or have only smoked for a few years. Because AATD causes COPD at an earlier age than usual, doctors may think you have asthma, and some people with AATD have asthma too.

Asthma + Lung UK says there is no current cure for AATD. Treatment focuses on slowing the progression of lung disease or treating the lung condition specifically. This is generally the same as for people who do not have AATD, and includes antibiotics for chest infections and, if there is very severe lung disease, a lung transplant.

AAT augmentation therapy gives AAT into the veins to increase levels in the body, with the aim of slowing the progression of COPD caused by AATD. Asthma + Lung UK says it is available in some other countries but is not currently approved in the UK, and is only available through clinical trials.

If AATD affects the liver, you might have blood tests and scans to monitor your liver, and liver disease is treated in its own right.

Asthma + Lung UK suggests a number of things to stay healthy with AATD. If you smoke, quitting slows down the development of COPD and improves your symptoms. Avoiding exposure to dust, fumes and chemicals, for example at work, matters because it might cause COPD to develop faster.

It also advises avoiding chest infections and colds, because infections can cause the lungs to become damaged more quickly. A cough that produces phlegm could be a sign of a chest infection, and you should see your doctor as soon as possible. Getting vaccinated against flu, coronavirus and pneumonia, eating well and keeping active are also suggested.

On alcohol, it says you do not have to avoid it completely, but should follow the NHS safe drinking guidance of drinking less than 14 units spread throughout the week.

Testing for AATD is done by blood test and usually begins with a GP or a respiratory or liver specialist, depending on whether the lungs or liver are involved. Asthma + Lung UK recommends seeing your GP if you have any symptoms of AATD.

Support is available from Asthma + Lung UK, which has a helpline and groups, and from Alpha-1 UK, the patient support group. Private respiratory or genetics consultations may be used for a second opinion, but ongoing care is usually coordinated through the NHS.