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Alpha-1 Antitrypsin Deficiency

Key points

  • Alpha-1 Antitrypsin Deficiency is a genetic condition that can lead to serious liver and lung problems
  • It’s also known as Alpha-1 or AATD
  • It affects both children and adults
  • You might be tested for Alpha-1 if you are diagnosed with a lung condition and also have liver or skin problems
  • If you have Alpha-1, it’s important to look after your liver by eating healthily, losing weight if you need to, exercising, and avoiding anything that can damage your liver
  • You should also protect your lungs by not smoking and avoiding lung infections.

What is Alpha-1 Antitrypsin Deficiency?

Alpha-1 Antitrypsin Deficiency (also called Alpha-1) is a genetic disorder that can lead to liver or lung disease. It’s inherited from your parents.

People with Alpha-1 don’t make normal alpha-1 antitrypsin, which is a protein made in the liver. The body uses this protein to control how other organs work. It’s especially important to protect the lungs from infections and smoke.

Alpha-1 is the most common genetic cause of liver disease in children.  In adults, it can cause:

  • Liver problems – the abnormal proteins get stuck in the liver and can lead to hepatitis, fibrosis, cirrhosis, hepatocellular carcinoma and liver failure. About 15 in 100 people with Alpha-1 develop cirrhosis
  • Lung problems – the lack of alpha-1 antitrypsin can cause chronic obstructive pulmonary disease (COPD), which includes emphysema and bronchitis.

Luckily, many people who have Alpha-1 never develop these problems. About 1 in 10 people with Alpha-1 will develop liver disease.

Alpha-1 affects about 1 in every 1,500 to 3,500 people. It’s most common in people of Caucasian backgrounds.


What are the symptoms of Alpha-1 Antitrypsin Deficiency?

If a baby is born with Alpha-1, the first signs may be:

  • Yellow skin and whites of the eyes (jaundice)
  • Swollen belly
  • Poor feeding.

Many babies born with Alpha-1 grow out of these liver problems and have normal liver function in childhood. They are still at risk of liver, lung and skin problems as they grow older. For some, the liver disease will gradually get worse and they may develop cirrhosis or liver failure when they are children.

Sometimes Alpha-1 first appears when a child is older, or when they are grown up. Symptoms in older children and adults include:

  • Jaundice
  • Feeling very tired (fatigue)
  • Poor appetite
  • Swollen belly and legs
  • Belly pain (in the top right of the belly)
  • Losing weight without meaning to
  • Pale poos and/or dark wee
  • Itching
  • Panniculitis (a skin condition where the fat under the skin gets inflamed)

Alpha-1 is often mistaken for asthma. The lung symptoms of Alpha-1 include:

  • Being short of breath
  • A cough that doesn’t go away
  • A lot of phlegm
  • Feeling tired, not having any energy
  • Not being able to exercise as much
  • A lot of chest infections, or not being able to recover from a chest infection.

How is Alpha-1 Antitrypsin Deficiency diagnosed?

Many people find out they have Alpha-1 because they go to the doctor with repeated lung infections or a cough. They might be diagnosed with emphysema, COPD, asthma, chronic bronchitis, or bronchiectasis.

Your doctor may test for Alpha-1 if you have:

  • COPD
  • Unexplained chronic liver disease
  • The skin condition panniculitis
  • Close family members with Alpha-1.

Alpha-1 is diagnosed with a blood test to look for levels of alpha-1 antitrypsin in the blood and what type of alpha-1 protein is in the blood. Doctors sometimes call this the ‘PI type”.

Other tests you may have include:

  • A liver scan to check for liver damage
  • A liver biopsy, where a small sample of the liver is removed to be examined in the lab. This is used to look for liver damage
  • Chest X-ray or CT scan
  • Lung function tests.

Why did I get Alpha-1 Antitrypsin Deficiency?

People with Alpha-1 inherit the condition from their parents.

There are 2 genes that control how your body makes alpha-1 antitrypsin. You get one from your mother and one from your father.

The ‘normal’ gene is called M. If you inherit 2 M genes (MM), one from each parent, the level of alpha-1 antitrypsin in your blood will be normal.

Sometimes instead of an M gene, one parent has a different gene called a Z gene. If you inherit a Z gene (MZ), you will have lower levels of alpha-1 antitrypsin but you won’t necessarily have any health problems. You will be a carrier.

If both parents have Z genes and you inherit both of them (ZZ), you will have very low levels of alpha-1 antitrypsin in your blood. This can cause health problems.

If both parents are carriers (MZ), for each child there is a 50% chance they will be a carrier, 25% chance they will be healthy, and 25% chance they will have Alpha-1.

If one parent has Alpha-1 (ZZ) and the other is normal (MM), all their children will be carriers (MZ).

 


How is Alpha-1 Antitrypsin Deficiency treated?

There is no cure for Alpha-1.

Children and babies with Alpha-1 may need treatment so they have enough nutrition to grow. They might need vitamin supplements. Medicine can be used to treat jaundice and itching.

Some adults with Alpha-1 who have serious lung problems may get weekly doses of alpha-1 antitrypsin in their veins. This is called augmentation therapy. This treatment is not used for liver disease in people with Alpha-1.

In adults with Alpha-1 and liver disease, the focus is on looking after the liver to prevent any further damage.

If liver damage is very far advanced, a liver transplant might be needed. If lung damage is very advanced, a lung transplant may be needed.

There are currently many studies going on into different medications that prevent the abnormal alpha-1 protein from damaging the liver. Hopefully these will provide some improved treatment for Alpha-1 liver disease in future.


Living with Alpha-1 Antitrypsin Deficiency

If you have Alpha-1, you will need to look after your liver by:

  • Losing weight if you are overweight
  • Avoiding alcohol
  • Exercising
  • Avoiding liver toxins.

People with Alpha-1 are also at much higher risk of developing COPD. You can look after your lungs by:

  • Not smoking tobacco
  • Avoiding second-hand smoke
  • Not working where it’s very dusty
  • If you have asthma, making sure it’s under control
  • Avoiding lung infections.

Information for carriers

Carriers may not realise they have Alpha-1, but they are still at higher risk of liver and lung problems.

If you are a carrier, it’s very important to look after your liver and avoid the risk factors for fatty liver disease.

It’s also important to look after your lungs and not to smoke.

 

Living Well

More information and support

Alpha-1 Organisation Australia 

Resource from Alpha-1 Organisation Australia: Questions people with Alpha-1 can ask their doctor

Alpha-1 Association of Australia

Lung Foundation Australia

Alpha-1 Foundation

References

American Liver Foundation. Alpha-1 Antitrypsin Deficiency

Canadian Liver Foundation. Alpha-1 Antitrypsin Deficiency

British Liver Trust. Alpha 1 antitrypsin deficiency (AATD)

Lung Foundation Australia. Alpha1-antitrypsin deficiency

Alpha-1 Association of Australia. Information

Alpha-1 Foundation. Testing & Diagnosis

Rare Awareness Rare Education. Alpha-1 Antitrypsin Deficiency (A1AD)

Townsend SA, Edgar RG, Ellis PR, Kantas D, Newsome PN, Turner AM. Systematic review: the natural history of alpha-1 antitrypsin deficiency, and associated liver disease. Aliment Pharmacol Ther. 2018 Apr;47(7):877-885. doi: 10.1111/apt.14537Alimentary Pharmacology & Therapeutics.

Reviewed August 2024

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