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.
Transcript
Alpha-1 Antitrypsin Deficiency is a rare genetic disease that affects both the liver and the lung.
Alpha-1 Antitrypsin is a protein that is made by the liver and travels in the bloodstream to various parts of the body, including the lung. When we are exposed to irritants such as cigarette smoke or have a bad cold, part of the body’s defence mechanism is to help fight that infection or irritant with inflammation.
If that inflammation just keeps on going and doesn’t stop, we end up with damage to the lungs and emphysema. Alpha-1 Antitrypsin is an antidote, if you like, to that. It stops the inflammation and then stops the damage to the lungs.
The Alpha-1 Antitrypsin is made in the liver, as I said before, and the genes that control the production of Alpha-1 Antitrypsin are defective in Alpha-1 Antitrypsin Deficiency. So you don’t make the protein, so it doesn’t travel to the lungs and protect the lungs. The other problem is the abnormal protein that is made in the liver sits inside the liver cells, crowds them, and stops the liver from functioning properly.
So the liver can then get inflamed itself with the abnormal protein and develop scarring and end-stage liver disease and liver failure. Some people with Alpha-1 Antitrypsin Deficiency, if they get scarring or cirrhosis of the liver, are also susceptible to liver cancer.
Alpha-1 Antitrypsin Deficiency is a genetic disease, so it is passed on from the parents to the child. To get Alpha-1 Antitrypsin Deficiency, you need two defective copies of the Alpha-1 Antitrypsin gene, and you usually inherit one from the mother and one from the father. People who have only one copy of an abnormal gene, like the mother and father, and one copy of the normal gene, don’t have any symptoms, so they wouldn’t know that they had Alpha-1 Antitrypsin Deficiency. It’s only when two such people get together and have a baby and that the defective gene from each parent is passed on, that the child will get Alpha-1 Antitrypsin Deficiency.
Alpha-1 Antitrypsin Deficiency is usually diagnosed with a series of tests, but the initial one is a blood test, which measures the abnormal protein and the type of abnormal protein.
Alpha-1 Antitrypsin Deficiency can present at any age, so it can present with liver disease as a baby, with jaundice and failure to grow, or it can present later in childhood liver disease or even in adulthood. It can also present with lung disease or emphysema, and that usually occurs in adulthood.
Once somebody presents with symptoms suspicious for Alpha-1 Antitrypsin Deficiency, the diagnosis is made with a blood test, which measures the abnormal Alpha-1 Antitrypsin protein in the blood.
The treatment for Alpha-1 Antitrypsin Deficiency depends on which organ is most affected. So if the liver disease is the predominant problem, then the person will undergo treatment for liver disease. This includes support with fat-soluble vitamins and nutrition, monitoring the liver for scarring and for something called portal hypertension, and also looking for the development of either cancer or liver failure. If the disease involves predominantly the lungs, there is a treatment that involves Alpha-1 Antitrypsin made from other people’s blood, which can be given as an infusion for people with very severe lung disease.
Very recently, in fact earlier this year, there was a very exciting article published in America from Philadelphia, where they have managed to correct the gene mutation in nine patients with Alpha-1 Antitrypsin Deficiency. So they used gene editing technology, which involved an injection into a bloodstream of a little particle that travelled to the liver. Inside the particle was a mini gene decoding machine, which travelled to the defective gene, found it, and corrected it. So this is extremely exciting news and paves the way for correction of such mutations in the future, and the earlier that that happens, the less likely there will be any kind of disease at all.
Many people with Alpha-1 Antitrypsin Deficiency lead very normal lives, have very minimal disease. The main things that they do is avoid cigarette smoke, either primary cigarette smoke, i.e. not smoking, but also not being in a household where other people smoke, and paying meticulous attention to infections and making sure that they don’t drag on for a long time, so perhaps earlier use of antibiotics for respiratory infections.
People would also need to be in regular contact with their gastroenterologist and respiratory physician to look after both the lungs and liver, and monitor for any effects of progression of the disease in either of those two body organs.
Alpha-1 Antitrypsin can be a confusing condition, so if you need more information and support, I would suggest that you look at the Liver Foundation website, where you’ll find some clearly explained information on the condition and its treatment. It’s also important because it is a variable condition that you speak to your own doctor because they will know how you’re affected and what you’re likely to need in the future.
There’s also excellent patient organisations, a particular big one in America is called Alpha-1 Foundation, which is a parent and patient organisation that both provides information and funds research.
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
Alpha-1 Organisation Australia holds regular patient peer support group meetings by video. To find out about meeting dates and times please email contactus.a1oa@gmail.com.
Resource from Alpha-1 Organisation Australia: Questions people with Alpha-1 can ask their doctor
Alpha-1 Association of Australia
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