Alpha-1 antitrypsin (A1AT) deficiency is an inherited genetic condition (a condition that can be passed on from your parents through your genes). It can lead to lung and, in some people, liver damage. Lung symptoms are the most common and include shortness of breath, cough and wheezing. Symptoms can worsen over time. At present, there is no cure for A1AT deficiency. Treatment aims at slowing down the progression of the disease.
Alpha-1 antitrypsin (A1AT) is a protein made by cells in the liver. It passes out from the liver into the bloodstream and can travel to the lungs. Its main function is to protect the lungs from damage caused by other types of proteins called enzymes. Enzymes are essential for the normal working and development of the body. In the lungs, certain enzymes called proteases help to fight infection, by removing bacteria and may also be released to try to protect the lungs from tobacco smoke. However, the activity of these protease enzymes needs to be balanced. If the balance tips and there is too much activity, then the tissue of the lungs can start to become damaged by the enzymes. A1AT helps to balance the protease enzymes in the lungs and stop lung damage.
Alpha-1 antitrypsin (A1AT) deficiency is an inherited genetic condition (a condition that can be passed on from your parents through your genes). It can lead to lung and, in some people, liver damage. It was first described in 1963 by Dr Sten Eriksson, a Danish doctor.
In the centre (nucleus) of most cells in the body there are 46 chromosomes arranged in 23 pairs. One chromosome from each pair comes from a person's mother and one from a person's father. Chromosomes are made of DNA. DNA stands for deoxyribonucleic acid. DNA forms a person's genetic material. A gene is the basic unit of this genetic material. It is made up of a sequence (or piece) of DNA and sits at a particular place on a chromosome. So, a gene is a small section of a chromosome. Each gene controls a particular feature or has a particular function in the body.
Someone with A1AT deficiency has a fault in a gene on chromosome number 14. This fault means that they still make A1AT but it is mis-shaped. It gets stuck in their liver and cannot pass out into their bloodstream and so to their lungs. There is not enough A1AT in their lungs to balance the protease enzymes and to protect their lungs from enzyme damage. The walls of the small air sacs in their lungs (the alveoli) can start to become damaged and destroyed by the enzymes, leading to a condition called emphysema. The alveoli have a good blood supply and the oxygen from the air that a person breathes in is transferred into their bloodstream from the alveoli. If the alveoli are damaged (as in emphysema), this oxygen transfer becomes affected.
Emphysema is one of the lung conditions that comes under the general term chronic obstructive pulmonary disease (COPD). COPD includes the conditions chronic bronchitis and emphysema. (Chronic means persistent and bronchitis is inflammation of the bronchi - the airways of the lungs.) Someone with COPD may have chronic bronchitis, or emphysema, or both.
In some people, because the abnormal A1AT gets stuck in the liver, it may also damage liver cells, causing scarring and liver disease. However, not everyone with A1AT deficiency develops liver disease. It is not fully understood why this is the case.
In order to develop A1AT deficiency, a person has to have two copies of the faulty gene on chromosome 14 - they have to have inherited a copy of the faulty gene from both of their parents. If they just inherit a copy of the faulty gene from one of their parents, they do not develop A1AT deficiency. They can still make enough normal A1AT to protect their lungs from damage. But, they are a carrier of A1AT deficiency - they can pass on the faulty gene to any children that they have.
There are many variations of the A1AT faulty gene. People with certain gene variations can be more severely affected than others. It has all got to do with the amount of normal A1AT that they are still able to produce. Only people with the lowest levels of A1AT in their blood will develop symptoms. A special test known as a phenotype test can show the gene variation that a person has. People who have two copies of the Z-type faulty gene (people who have the ZZ phenotype) produce the least amount of normal A1AT and are most severely affected.
Between 1 in every 3,000 to 5,000 people in the UK have A1AT deficiency. Around 1 in 25 people carry an A1AT faulty gene. This makes A1AT deficiency one of the most common inherited conditions in the UK.
Because of the variations of the A1AT faulty gene mentioned above, there is a wide range of symptoms that people with A1AT deficiency may have. Some people with A1AT deficiency have very few or no symptoms, whilst others are more severely affected. Also, the variations in the faulty gene mean that symptoms can progress more quickly in some people than in others. Someone with A1AT deficiency can develop lung symptoms or liver symptoms, or sometimes both.
These are the most common. If lung symptoms develop, it is not usually until a person is in their 40s. However, people who smoke and who also have A1AT deficiency tend to develop symptoms much earlier, sometimes as early as in their 20s. Symptoms can include:
Rarely, a baby with A1AT deficiency can develop jaundice and liver inflammation (hepatitis) soon after they are born. It is thought to be due to a build-up of A1AT in the baby's liver while they were developing in their mother's womb. Most of the time, the child will grow out of their liver problems so that, by the time they reach puberty, they may only have mild liver abnormalities. However, in some rare cases, a baby or young child can develop liver failure.
Many adults with A1AT deficiency will show some signs of mild liver damage. But, in a few, more severe liver damage can occur, leading to scarring (known as liver cirrhosis) and chronic liver disease where their liver isn't working very well.
Because A1AT deficiency runs in families, if a person is found to have A1AT deficiency, other family members should also be tested.
Various other tests may be suggested to determine how severely a person is affected. They may be repeated at intervals to monitor the progression of the disease. Tests may include:
At present, there is no cure for A1AT deficiency. Most people are diagnosed with the condition after they have developed lung or liver disease. Treatment aims at slowing down the progression of the disease.
For those who develop emphysema, treatment is similar to that for COPD that is not caused by A1AT deficiency. (For further details about the treatment of COPD, see separate leaflet 'Chronic Obstructive Pulmonary Disease'.)
Briefly, treatment for A1AT deficiency may include the following.
Smoking speeds up the development of lung disease in people with A1AT deficiency, so stopping smoking is very important.
This is an option in a very small number of cases. Sometimes large air-filled sacs (called bullae) develop in the lungs in people with COPD. A single large bulla might be suitable for removal with an operation in some people. This can improve symptoms in some people. Lung transplantation may also be an option in some cases.
It is possible to treat people with A1AT deficiency by giving them the A1AT that they are lacking in their bloodstream, in medicine-form. It can be given intravenously (into a vein). However, there is a question about the benefits of this treatment. There are no well-designed research studies that have absolutely proven that giving this treatment helps to improve survival or slow down the rate of progression of the lung disease. The National Institute for Health and Clinical Excellence (NICE) in the UK does not recommend treatment by replacing A1AT at present due to the lack of evidence for its benefit. However, this decision has been criticised by some people. The medicine is available and is used in some other countries.
Because different people with A1AT deficiency can have different degrees of symptoms, and because the disease progresses more slowly in some people and more quickly in others, the prognosis (outlook) is very variable. Some people with A1AT deficiency may just have mild wheezing and mild shortness of breath in their 70s, whilst others may have severe lung disease in their 20s or 30s.
Although there is no cure for A1AT deficiency, early diagnosis and treatment can help to slow down the rate of progression of the disease. And, with regular monitoring and careful management of their condition, many people with A1AT deficiency can stay well and healthy.