This section includes information designed to help you understand more about Alpha-1-Antitrypsin Deficiency (AATD). We encourage you to click on the links below to learn more about:

What is AATD?
Diseases caused by AATD
How to identify the signs and symptoms of the disease
Side Effects
Genes related to AAT
How the disease is inherited
Diagnosing the disease
Treatment options for AATD
How to manage the disease

Alpha-1-Antitrypsin Deficiency, in short AATD, is an inherited disorder that causes significant reduction in the naturally occurring protein Alpha-1-Antitrypsin (AAT).

Scientists also call this protein serine proteinase inhibitor because it inhibits not only trypsin but also other serine proteinases.

Emphysema
Lung disease is the most common problem associated with a deficiency of AAT. AAT is produced by the liver and shields the body from damage caused by the protein neutrophil elastase.

Under normal conditions, neutrophil elastase helps fight bacteria that cause infection. However, if not neutralized by AAT, neutrophil elastase can destroy healthy lung tissue.

Alveoli are tiny air sacs in the lungs, which are responsible for taking in oxygen and releasing carbon dioxide. When adequate levels of AAT are not present, the enzymatic activity of neutrophil elastase is not neutralised and the fine elastic tissue supporting the alveoli is destroyed. Over time, enough alveoli are destroyed to cause the lungs to lose much of their elasticity, resulting in emphysema. Therefore, people with a deficiency of AAT are at high risk for developing emphysema.

Emphysema is a chronic condition defined as a permanent enlargement of the air sacs distal to the terminal bronchioles consequent to destruction of the alveolar wall.

Emphysema is a condition in which there is an over-inflation of structures in the lungs known as alveoli or air sacs. This overinflation results from a breakdown of the walls of the alveoli, which causes a decrease in respiratory function and often breathlessness.

Liver disease
When less AAT is released from the liver to the bloodstream, increased amounts of AAT remain in the liver; this can result in liver disease. When liver disease develops, it usually manifests itself in infants as jaundice and hepatitis. However, liver disease may also develop in children and adults as cirrhosis. Rarely, patients may develop significant lung disease and liver disease at the same time. Another rare problem in patients with AATD is vasculitis, and inflammation of the blood vessels.

Currently, most people who are tested for, and diagnosed with AATD, have suffered for years with unexplained and poorly controlled lung problems.
The underlying diagnosis of AATD is frequently missed since symptoms of the lung disease caused by AATD are identical to those of other common lung diseases such as asthma or chronic obstructive pulmonary disease (COPD). Lung symptoms often appear between the ages of 30 and 60, although smokers may develop symptoms about ten years earlier than non-smokers
Typical symptoms include the following:

• Cough
• Shortness of breath following exercise
• Decreased exercise tolerance
• Wheezing, with or without upper respiratory tract infection
• Sputum (or phlegm) production
• Frequent lung infections
• History of suspected allergies or asthma

Urine Incontinence
As AATD-patient you might get problems with urine incontinence, as you cough a lot. Do not hesitate to talk to your doctor about how to relieve the problem. Among other things pelvic floor exercises can help you.

As AATD is a hereditary disorder, the answers to the questions whether and to what extent an individual may be affected can be found in so-called AAT genes.

The most common AAT gene is the M gene, followed by the S and the Z gene. Soon after the discovery of AAT deficiency, it was recognised that there is an association between the inherited AAT genes and the levels of AAT in serum. M genes are associated with normal AAT levels, whereas S and Z are associated with reduced levels, with the levels associated with Z lower than S.

The majority of individuals who inherit one Z gene and another gene, such as M (PiMZ), are considered to be carriers of Alpha-1. Those individuals usually have AAT serum concentrations below the normal limits. In order to determine the type of genes you have inherited, your physician will perform a special blood test called genotyping.

Since AATD is inherited, blood relatives of anyone with AATD have an increased risk of having AATD.

Every person inherits two AAT genes, one from each parent, and the two parental AAT genes are codominantly expressed. A person has a much higher risk of developing emphysema if he or she inherits two abnormal genes. People with one abnormal gene and one normal gene are called carriers. They have some risk of developing emphysema and they can pass the abnormal gene on to their children.

In families in which one parent has a low level of AAT (two abnormal Z genes) and the other parent has a normal value (two normal M genes), all children have intermediate AAT concentrations (one normal M gene and one abnormal Z gene). These people are called carriers.

When both parents have intermediate AAT concentrations (one normal M gene and one abnormal Z gene), the children may have low (ZZ), intermediate (MZ) or normal (MM) values. Brothers and sisters of a patient have mathematically a 1 in 4 chance of inheriting two Z genes (ZZ) and also having AATD. Siblings of an Alpha-1 patient should be tested.



Since most people do not have a Z gene, it is highly unlikely that a husband or wife of a carrier is also a carrier. However, even if he or she is not a carrier, there is a 50 percent chance that the abnormal Z gene is given to his or her offspring, making them carriers. The partner of an Alpha-1 patient may want to be tested to rule out the possibility that he or she is a carrier.

AATD can be diagnosed with blood tests, which measure the amount of AAT present in the blood. The AlphaKit^® – currently available in Germany, Austria and Switzerland – allows testing to be performed with only a few drops of blood dried onto a filter paper. A laboratory will measure the AAT level in the dried blood sample. People with AATD typically have only 10 to 15 percent of the normal amount of AAT in their blood, so a very low result would suggest AATD.

AATD can be confirmed by a specialised blood test called phenotyping. Phenotyping will detect the variant AAT protein. Phenotyping also is available to detect the carriers of AATD. Therefore, it is useful for testing blood relatives of persons with AATD. Phenotyping results are expressed in letters such as M, S, Z or other letters of the alphabet, which designate the specific genes one has inherited. The most common genetic phenotype among people who have AATD is PiZZ.

There is a specific pharmacological treatment that helps restore through augmentation therapy the natural balance of enzymes in the lungs and protects from the damage caused by neutrophil elastases. The therapy is administered intravenously, once a week. Given as prescribed it raises the blood and lung levels of AAT. Please ask your doctor.

• Stop smoking immediately
• Go in for sports
• Pay attention to healthy eating habits
• Avoid environmental hazards
• Respiratory illness should be treated promptly and aggressively
• Augmentation therapy with Alpha-1 Proteinase Inhibitor, if indicated