Newly Diagnosed

You have been told by your doctor that you have Alpha-1 Antitrypsin Deficiency or that the level of Alpha-1 Antitrypsin in your bloodstream is abnormally low. This page will attempt to explain, using the minimum of technical terms, what this means.

What is Alpha-1 Antitrypsin Deficiency?

Alpha-1 antitrypsin deficiency is a hereditary condition that occurs predominantly in people of European extraction. In the United Kingdom about one in 2,500 people have this condition. It is the most common genetic cause of pulmonary emphysema in adults and liver disease in children. In addition, there is evidence that infants, young children, and school-age children with the deficiency also have an increased likelihood of developing bronchial disease. According to current data, only around 2 to 5% of Alpha-1 patients are affected by liver disease in adult age.



Alpha-1 antitrypsin deficiency (AATD) was first described as a hereditary disease by Laurell and Eriksson in 1963. Since its discovery our knowledge of the condition has expanded considerably, yet alpha-1 antitrypsin deficiency remains a largely unknown disease. People, like you, who have been diagnosed with the condition often have waited many years between the first appearance of symptoms and a correct diagnosis. In part this is because the symptoms often point to other, more common, complaints. The breathlessness that comes with chronic obstructive pulmonary disease (COPD) or signs such as jaundice, inflammatory liver disease and cirrhosis (scarring) of the liver are not always attributed to alpha-1 antitrypsin deficiency. The number of undetected Alphas is therefore probably very high.


General therapeutic measures

Alpha-1 antitrypsin deficiency is not yet curable. At present only the symptoms can be treated by appropriate therapeutic measures. Besides specific treatments for the lungs and liver, all Alphas should take precautions to avoid infections. They should have a flu vaccination once a year and also receive immunisation against hepatitis A and B. SMOKING and alpha-1 antitrypsin deficiency are a deadly combination. For Alphas with liver disease the rule is NO ALCOHOL.


How does Alpha-1 Antitrypsin Deficiency develop?


Alpha-1 antitrypsin deficiency is a genetic defect that causes our liver either not to produce the protein called alpha-1 antitrypsin (AAT) or to produce this substance with errors in the structure of its molecules. These badly formed molecules fold incorrectly and become, by and large, unable to leave the liver. In contrast to the rest of the body, the problem in the liver is not a lack of but rather an accumulation of abnormally folded protein in the liver cells, and this damages them. In turn, the damaged cells can lead to prolonged jaundice in the newborn or bile stasis or chronic liver disease in children. Affected children often have poor appetite and fail to thrive. Although 10 to 20% of children with alpha-1 antitrypsin deficiency have liver involvement, that figure drops to 2 to 5% with increasing age. However, there are Alpha-1 patients who do not develop any symptoms until adult age. They are then more likely to develop cirrhosis (scarring) or cancer of the liver. As yet there is no specific drug treatment for liver alphas.



We inhale and exhale approximately 0.5 litres of air with every breath. This equates to between six and eight litres of air circulated per minute, or around 10,000 litres a day. We also draw exhaust gases, dust, cigarette smoke (actively and passively), pollen, bacteria and much more into our lungs with every breath. The lungs defend themselves against these irritants with a substance (an enzyme) which is secreted by white blood cells and which keeps our lungs clean. Alpha-1 antitrypsin serves to stop this substance from attacking healthy lung tissue. If it is absent or in short supply, this protective function is insufficiently carried out, resulting in damage in the form of pulmonary emphysema, where the tiny air sacs are destroyed. The walls between the air sacs fuse, the lung tissue loses its elasticity and large cavities form and these fill with residual air. Shortness of breath develops – first during physical exertion, but in the advanced stage even at rest. Pulmonary emphysema is irreversible, i.e. the destruction of healthy lung tissue cannot be made good again. This process cannot as yet be halted, but it can be significantly slowed down by supplying alpha-1 antitrypsin in the form of weekly infusions (augmentation therapy).

In rare cases alpha-1 antitrypsin deficiency also damages other organs such as the skin (panniculitis or the inflammation of subcutaneous fatty tissue), the pancreas and blood vessels (vasculitis).



Our ability to make AAT is inherited through genes passed on by both parents. We have about 25,000 pairs of genes in every cell of our body. Our genes determine how our bodies grow and develop. One of these genes is known as Protease Inhibitor (Pi). It is this gene that makes AAT.

We all have two copies of the Pi gene. We inherited one copy from our mother and the other from our father. When we have a child we pass one of our Pi genes, and our partner provides the other.

There are more than 75 different varieties of the Pi gene. Most of these varieties result in normal levels of AAT in the blood, but some result in low levels or no AAT. The most common varieties are labelled M, S and Z.

  • Most people have two copies of type M (written PiMM) and have normal levels of AAT in their bloodstream.
  • Type Z results in low levels of AAT in the blood stream and someone with two copies of the Z type (PiZZ) has AAT Deficiency.
  • Someone with one copy of type Z and a copy of type M (PiMZ) is known as a carrier of AAT deficiency.
  • Type S results in slightly reduced levels of AAT, so someone with PiMS will probably have less AAT than someone with PiMM but more than someone with PiMZ.

Your doctor may have arranged for various tests to be performed before you were informed of the diagnosis. The simplest of these is the level of AAT in the bloodstream. This can normally differentiate between Alphas and carriers of a faulty gene. More advanced laboratory tests look at the molecules of AAT and this can determine the types M, S, Z etc. This is called phenotyping. The most advanced tests analyse the Pi genes themselves. This complex and expensive process is called genotyping and it is used to find the extremely rare varieties of the Pi gene.



If you have been diagnosed as a carrier of AATD (your doctor may have used the words heterozygous or PiMZ) then how does this affect your children?

If your partner is normal, that is to say PiMM, then the implications for your children are as follows:-

There are four ways of selecting two Pi genes, one from the mother’s two Pi genes and one from the father’s two Pi genes. Each child has just one of these four possibilities. The diagram shows an equal number of Carrier and Normal combinations and therefore each child will have a 50-50 chance of being a carrier.


However, if your partner is also a carrier then there is a 1 in 4 chance that any child born to you both will be an Alpha. Two of the four possibilities are that the child will be a carrier.


If you have been diagnosed as having Alpha-1 Antitrypsin Deficiency (your doctor may have used the words homozygous or PiZZ) then your children will definitely be affected.

  • If your partner is normal, that is to say PiMM, then all your children will be carriers. They will carry one Z gene from you and one M gene from your partner. There is no possibility that a child can be a full Alpha.
  • If your partner is a carrier then each child will be either a carrier or a full Alpha with equal probability.

Signs of Alpha-1 Antitrypsin Deficiency

Genetic mutations were invented by evolution in order to adapt life forms optimally to their surroundings. Alpha-1 antitrypsin deficiency occurred because it probably protected people from even worse conditions in the past. Provided that the condition is diagnosed early, the development of lung disease due to alpha-1 antitrypsin deficiency can be delayed for years or possibly prevented altogether.


Who should be tested?

It is generally accepted that the following group of people should be test for AATD.

  • All patients with frequently recurrent infections
  • All patients with COPD (chronic obstructive pulmonary disease)
  • All children, adolescents and adults with asthma
  • Newborn, children and adults with liver disease of unknown origin
  • All individuals in whose family alpha-1 antitrypsin deficiency has occurred

Since you have been diagnosed as having the genetic condition then it is very important that your close blood-relations are also tested for it. This way preventative measures against emphysema and liver scarring can start as soon as possible.

Testing for the deficiency can only be performed by medically qualified people and will probably be very similar to some of the tests performed on you (AAT level in a blood sample, phenotyping, Lung Function Tests, etc).

From time to time everyone suffers from flu-like symptoms with a cough, nasal congestion and hoarseness. Children under the age of one year are especially susceptible, because they first have to build up their immune system. With this caution about panic reactions, you may wish to tell more distant relatives of your condition and suggest that they be tested. They should think of the possibility of alpha-1 antitrypsin deficiency if any of the following symptoms occur alone or together:




Frequent infections
Frequent coughs, phlegm production
Shortness of breath
Dark urine
Distressing itching
Failure to thrive
Inflammation of the liver

Remember that these are just guidelines and only a medical doctor can give an authoritative diagnosis.


What can you do about it?

When first diagnosed most Alphas experience a turmoil of emotions – anger at the unfairness of life, guilt at passing on a defect to their children, fear of the unknown and many more. How they cope with this varies from person to person. One Alpha may use a particular stress management technique, another may find consolation in faith and a third may simply accept it all.

The other thing that you can do is look at your lifestyle and see what changes may help you.

Keep your body healthy with a balanced diet and regular exercise. Infections and other illnesses are more challenging to Alphas than to most people. Improve your defences.

Smoking is especially harmful for people with AATD. Tobacco smoke releases increased amounts of the lung-damaging enzyme, thereby destroying more lung tissue. In addition, the smoke destroys what little AAT may be present in the lungs. If you smoke, you should quit as soon as possible. Certainly it is no easy matter to stop smoking, but you can do it. There are programmes to help you kick the habit and your GP will be able to advise you further. Even passive smoking is harmful. Ask everyone who smokes near you to refrain from doing so.

Keep away from environmental pollutants such as open fires, petrol fumes, paints and solvents, dust, etc. If there are air-borne irritants or fumes at your place of work then wear a mask.

Heed any air quality warnings on the radio or television, especially in the hot summer months. If ozone levels are high, try not to venture outside and avoid excessive physical exertion.

Avoid contact with anyone who has a cold or flu. In addition, try to stay away from crowds and large gatherings, especially in winter.