Alpha-1 Antitrypsin Deficiency

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What is Alpha-1 antitrypsin deficiency?

Alpha-1 antitrypsin deficiency is an inherited condition that can damage your lungs and, in some people, the liver. Abnormal genes can result in a deficient of a protective protein known as AAT, which normally protects your lungs from harm.

Symptoms of Alpha-1 antitrypsin deficiency

Lung symptoms

Shortness of breath, especially when you exercise or exert yourself
Wheezing, a whistling sound when you breathe
A cough that does not go away, often with mucus
Feeling very tired
Chest colds that keep coming back

Lung symptoms usually start between the ages of 30 and 50, though they can also start later in life.

Liver symptoms

Some people with Alpha-1 antitrypsin deficiency develop liver problems, either as babies or later as adults.

Yellow or grey skin and eyes (jaundice)
Itchy skin
Swelling in your legs or your tummy (abdomen)
Being sick and bringing up blood

Rarely, the first sign of Alpha-1 antitrypsin deficiency is painful, red bumps on the skin.

Causes of Alpha-1 antitrypsin deficiency and who's at risk

Alpha-1 antitrypsin deficiency is caused by a change in the SERPINA1 gene, which you're born with, one copy inherited from each parent, and which affects how your body makes a protein called AAT: sometimes too little, sometimes AAT that doesn't work properly, and rarely none at all. The combination you inherit affects your risk of lung or liver problems, ranging from little or no extra risk to a much higher one. Alpha-1 antitrypsin deficiency affects around 1 in 3,000 people in the UK (Asthma + Lung UK).

Who's at risk

You have a close family member with Alpha-1 antitrypsin deficiency, since the condition runs in families
You're of European ancestry, as Alpha-1 antitrypsin deficiency is most common in this group
You smoke, or are regularly around smoke or lung irritants, which raises your risk of lung damage even if you only carry one changed copy of the gene

Types of Alpha-1 antitrypsin deficiency

The way Alpha-1 antitrypsin deficiency affects you depends on which combination of gene copies you've inherited. These are described using letters: M is the normal version of the gene, while S and Z are the two most common changed versions. Each combination can present with its own set of symptoms, ranging from none at all to significant lung and liver problems.

MM (normal): the most common combination, which carries no increased risk of lung or liver disease. AAT levels are normal.
MZ, MS or SS (carrier types): AAT levels are reduced but usually sufficient. Many people have no symptoms, but it's still sensible not to smoke and to keep alcohol within moderate limits
SZ: AAT levels are low enough to raise the risk of lung disease, and some people may develop liver problems.
ZZ: this is the most serious of the common combinations, associated with early-onset lung disease and liver disease.
Null combinations (rare): these copies make no AAT protein at all and are strongly associated with lung disease.

How is Alpha-1 antitrypsin deficiency diagnosed?

Doctors diagnose Alpha-1 antitrypsin deficiency using a blood test that measures how much AAT you have in your blood. If your level is low, the lab will run further tests, called phenotyping, to work out exactly which gene changes you have.

Occasionally, a low AAT level is picked up by chance, during a routine blood test called serum electrophoresis that's done for another reason.

If genetic testing is needed, your doctor will arrange for a small blood sample to be sent to a specialist genetics laboratory. This usually takes about four weeks to come back.

You may have other tests too, to check how Alpha-1 antitrypsin deficiency has affected your lungs or liver:

Blood tests, including genetic testing
Chest X-rays and CT scans
Breathing tests (pulmonary function tests)
A liver ultrasound or a scan called elastography
A liver biopsy, where doctors take a small sample of liver tissue to check for damage

You may also be tested for hepatitis C if you're diagnosed with Alpha-1.

How is Alpha-1 antitrypsin deficiency treated?

Treatment cannot reverse damage that's already happened, but it can help stop things getting worse and ease your symptoms. What's right for you depends on which organs are affected and how severe your symptoms are.

Non-surgical treatment options

Augmentation therapy: a drip (IV infusion) of AAT collected from blood donors, usually given regularly to raise your AAT levels. It cannot reverse existing lung damage, but it can help prevent further damage. It does not protect your liver
Medication: inhaled steroids and medicines called bronchodilators can make breathing easier by reducing inflammation and opening your airways
Oxygen therapy: extra oxygen if your blood oxygen levels are low
Pulmonary rehabilitation: breathing exercises and physiotherapy to make breathing easier
Smoking cessation support: help to stop smoking, if you smoke

Surgical treatment options

Lung transplant: if your lungs are severely damaged, a lung transplant may be an option. It can improve your quality of life, but it will not cure Alpha-1 antitrypsin deficiency
Liver transplant: if your liver is badly scarred, a liver transplant may be recommended. A healthy donor liver should make normal AAT

If you smoke, stopping is one of the most effective things you can do, whichever gene combination you have. Keeping alcohol within moderate limits is also recommended, especially if you have a Z-type combination, as this can affect your risk of liver disease. If you already have lung or liver disease, you may be referred to a specialist respiratory or liver team for ongoing care.

When should I see a doctor?

Speak to your doctor about getting tested for Alpha-1 antitrypsin deficiency if you have ongoing lung or liver symptoms, or if a family member has been diagnosed with it. It's also worth asking about testing if you have COPD, asthma or bronchiectasis, particularly if this started at a young age or without the usual risk factors, such as smoking.

If you've already been diagnosed with Alpha-1 antitrypsin deficiency, contact your doctor if you notice any new symptoms, have questions about your care, or are struggling to manage your symptoms day to day.

FAQs

Is Alpha-1 antitrypsin deficiency the same as genetic emphysema?

Alpha-1 antitrypsin deficiency is sometimes nicknamed 'genetic COPD' or 'genetic emphysema' because it's a genetic cause of these lung conditions, rather than a separate disease. Having Alpha-1 antitrypsin deficiency increases your risk of emphysema and COPD, but not everyone with Alpha-1 antitrypsin deficiency goes on to develop them, especially if they never smoke.
Can Alpha-1 antitrypsin deficiency be prevented?

You cannot prevent Alpha-1 antitrypsin deficiency itself, since you're born with the gene change that causes it. However, not smoking or vaping, avoiding lung irritants such as dust and chemicals, and keeping alcohol within moderate limits can all reduce your risk of lung and liver damage.
Will I pass Alpha-1 antitrypsin deficiency on to my children?

This depends on your own gene combination and your partner's. If you have Alpha-1 (two changed gene copies) and your partner has no changed copies, all of your children will carry one changed copy, but none will have Alpha-1 antitrypsin deficiency itself. If you're a carrier (one changed copy) and your partner has no changed copies, each child has a 1 in 2 chance of also being a carrier
What's the outlook for someone with Alpha-1?

This varies a lot from person to person. Alpha-1 antitrypsin deficiency may not affect how long you live, especially if you never smoke, but some people do go on to develop serious lung or liver complications. Things that affect your outlook include how early you're diagnosed, which type of Alpha-1 antitrypsin deficiency you have, how much organ damage you already have, and whether you smoke.
Should my brothers, sisters or other family members be tested?

Testing is generally recommended for siblings of someone diagnosed with Alpha-1 antitrypsin deficiency. There's no single UK guideline on testing wider family members, though international respiratory guidelines recommend sibling testing as good practice. Testing other relatives or partners can be considered case by case, but it isn't routinely recommended.
If I'm a carrier, like MZ or MS, am I at risk?

Carriers usually have lower, but still sufficient, levels of AAT, and are not thought to be at significant extra risk of lung or liver disease. It's still a good idea not to smoke, and to keep alcohol within moderate limits, as these can add to any small risk that's there.

Alpha1-antitrypsin deficiency