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1-antitrypsin deficiency

It is a hereditary or genetic disease in which affected people have low levels of the protein Alpha-1-antitrypsin in the blood and in the tissues, which increases the risk of suffering from lung and/or liver diseases, among others. .

Consequences of Alpha-1 deficiency

AAT deficiency has consequences in different organs and systems of our body.

In the lungs³⁵

If the AAT protein is not produced in sufficient quantity, the lungs do not have sufficient protection against different substances, leading to a emphysema.

Emphysema produces the destruction of the walls of some alveoli while others are not able to empty completely, so there is an accumulation of air inside the lungs causing hyperinflation. In addition, this prevents gas exchange from being carried out normally.

The fact that the lungs do not empty completely makes the person with emphysema have to make a greater effort to breathe, because they want to get air into a busy place, producing the sensation of dyspnea or shortness of breath. As the damaged alveoli do not help the airways to remain open, they close, thus blocking the passage of air.

They may also appear bronchiectasis, that is, sac-like deformities of the airways in which a lot of mucus accumulates, which facilitates the appearance of infections.

What is alpha-1-antitrypsin?¹²³

Alpha-1-antitrypsin (AAT) is a protein that is produced in the liver and has the function of protecting the lungs and other organs from substances that can damage them.

The origin of the AAT²³⁴ protein

Inside our cells is DNA, which is a code that determines our characteristics and how our body works. This code is made up of genes, small information storage units of living beings. Each gene has the information needed to make one or more proteins. Proteins are the molecules that do the work.

DNA is organized in our cells in the form of chromosomes. We receive half of our chromosomes from our mother and the other half from our fathers. In our cells there are 23 pairs of chromosomes.

In the case of AAT, the information is found in a gene called SERPINA1 located on chromosome 14.

There are different types of this gene and they are named with a capital letter. Depending on which gene this is, different things can happen.

this variant produces a protein that works correctly and in sufficient quantity

this variant causes the protein not to be produced

both variants produce defective proteins

One copy of this gene we have received from the mother and the other from the father. For the disease to occur, both copies must be defective, these being the most frequent combinations:

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How is it transmitted?²

It is a recessive condition, that is, two abnormal copies of the gene are needed to develop the disease. People who have one normal SERPINA1 gene and one abnormal gene are called carriers. These people, due to their defective gene, will have a lower than normal amount of AAT but not as it happens to lead to health problems.

Carriers can pass on their abnormal gene to their children, and those children can inherit two normal genes and be healthy; one normal and one abnormal, becoming carriers; while if both genes are abnormal then it would have the deficiency.

The fact of having the deficiency does not imply that you suffer from a disease, but rather that there is an increased risk of suffering from lung or liver diseases. Therefore, many people with deficiency who do not smoke do not develop lung disease or related symptoms.

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Source: https://europeanlung.org/es/information-hub/factsheets/alpha-1-antitrypsin-deficiency/

Is Alpha-1-Antitrypsin Deficiency very common?²

Although it is considered a rare disease, it is one of the most common hereditary diseases in the world.

The slowness in diagnosis, which usually takes an average of 7 years, contributes to its being considered rare.

This delay in diagnosis may be due to:

The difference in symptoms between some affected people and others.
Diseases that affect the lungs and liver can be due to many other causes.

in the liver¹

Sometimes the alpha-1-anttrypsin protein cannot pass into the blood and remains accumulated in the cells that produce it in the liver, which can lead to:

Neonatal jaundice: In newborns, hepatitis can occur, causing bilirubin to accumulate. This causes the baby's skin and mucous membranes to turn yellowish. It usually resolves in a few days, although there are cases in which it can progress to chronic hepatitis or severe liver failure
Hepatitis and cirrhosis: Liver failure can evolve, in adulthood, to a permanent inflammation of the liver (chronic hepatitis) that in its most advanced phases ends up covering the liver with scars (cirrhosis) that prevent it from performing its function.

In other organs¹

In addition to the lungs and liver, AAT deficiency can also affect:

The skin: Subcutaneous fat, which is just under our skin, becomes inflamed, producing panniculitis, which leads to the appearance of ulcers.
Blood vesels: Which also become inflamed, giving rise to vasculitis.
Muscles: Although it is not yet clear, there are possibilities that AAT deficiency is associated with a disease called Fibromyalgia. This produces a lot of fatigue and pain at the muscle and tendon level.

Signs and symptoms⁶

When the lungs are affected The symptoms and causes that tend to appear are:

Shortness of breath while exercising and even at rest
Wheezing in the chest when breathing (wheezing)
Persistent cough
Frequent respiratory infections
Persistent phlegm production
History of suspected allergy and/or asthma
sinus infections

If AAT deficiency affects the liver The symptoms that we can find are:

Increased enzymes produced by the liver in the blood.
Yellowing of the eyes and skin (jaundice)
Enlarged liver and/or spleen
Accumulation of fluid in the abdomen (ascites)
Cirrhosis
Persistent itching sensation.
Noticeable changes in energy level or fatigue
Blacker, purplish, darker, or paler stools.
Lack of appetite.

How is it diagnosed⁶

Who should be tested?³

Diagnostic tests for Alpha-1 Antitrypsin deficiency are recommended for those with:

- COPD (Chronic Obstructive Pulmonary Disease)
- Poorly controlled asthma despite correct treatment
- Bronchiectasis.
- Symptoms of shortness of breath (dyspnea) and chronic cough in many family members.
- Liver disease of unknown cause.
- Panniculitis or vasculitis of unknown cause.
- Blood relatives of a person with Alpha-1 Antitrypsin Deficiency.
- People who have had a proteinogram showing a decrease in alpha globulins.

Treatment

Although AAT Deficiency is a disease that has no cure, it can be controlled. The sooner it is diagnosed, the sooner proper treatment can be implemented.

When a person is diagnosed with AAT Deficiency, it is necessary to make a series of changes and adjustments both in their lifestyle and in their environment.