Alpha-1-antitrypsin deficiency

Synonyms in a broader sense

English: alpha1-antitrypsin deficiency

  • Laurell-Eriksson syndrome
  • Alpha-1-protease inhibitor deficiency


Alpha-1-antitrypsin deficiency is, as the name suggests, the absence of the protein alpha-1-antitrypsin, which is produced in the lungs and liver. It is therefore a metabolic disorder. This disease is inherited autosomal recessively. It occurs with a frequency of 1:1000 to 1:2500 in the population.


The cause of alpha-1-antitrypsin deficiency lies in an error in inheritance. The deficiency of the protein alpha-1-antitrypsin is inherited autosomal recessively. This means that the disease is inherited independently of sex and only really breaks out when two defective gene copies are present.

Both parents must therefore either be affected or be carriers of the genetic information. Only a single gene that carries the defective information cannot cause any harm. The defect is located on chromosome 14, which carries the gene responsible for the synthesis (production) of alpha-1-antitrypsin in healthy individuals.

Alpha-1-antitrypsin is an endogenous protein which is mainly produced in the cells of the liver. It has the task of inhibiting protein-splitting enzymes. Alpha-1-antitrypsin deficiency leads to an excessive activity of these protein-splitting enzymes.

This results in the breakdown of the body’s own tissue. Its most important task is to inhibit the enzyme elastase of the leukocytes. This enzyme breaks down the elastase in the wall of the pulmonary alveoli.

Symptoms and complaints

Since the production of alpha-1-antitrypsin takes place mainly in the lungs and liver, the damage and impairment also occurs here. The breakdown of the body’s own tissue therefore also takes place there. There is a very wide variability in its expression.

In patients with severe lung damage, liver involvement is surprisingly rare and vice versa. The age distribution is also quite different. While some already have end-stage lung disease in the third to fifth decade of life, others have no lung damage at all by the age of 30.

Sometimes patients with Alpha-1-Antitrypsin Deficiency have inflammation in the subcutaneous fatty tissue. This is delimited and reddish. It’s called panniculitis.

There are other causes for this inflammation. The exact mechanism of origin is not yet known. This local inflammation can be very persistent and painful.

Another symptom on the skin is blue discoloration (cyanosis). This is caused by the lack of oxygen saturation of the blood when the lungs are involved, such as emphysema. Not only the skin then has a bluish tinge, but also the mucous membranes and the tongue.

Cyanosis occurs in many clinical pictures and is therefore not specific for Alpha-1-Antitrypsin Deficiency. The protein alpha-1-antitrypsin is not only found in the liver, but also in the lungs. Here it also plays an important role in good lung function.

A deficiency of this alpha-1-antitrypsin leads to the breakdown of important components of the lung, resulting in the continuous destruction of lung tissue. Alpha-1-antitrypsin deficiency causes emphysema in the lungs. Pulmonary emphysema is understood to be an over-inflation of the lungs.

This is due to the inflammatory changes in the lung structure. The walls of the pulmonary alveoli are no longer stable enough and are destroyed by enzymatic degradation. This creates large cavities in the lungs from which the inhaled air can no longer escape.

This is why it is called over-inflation of the lungs. Furthermore, chronic obstructive pulmonary disease (COPD) develops in early adulthood. The gas exchange in the lungs is disturbed, resulting in a lack of oxygen in the blood.

A cough with sputum is typical in COPD. A feeling of breathlessness is also typical in the advanced stages. This can also have consequences for the heart, so that the heart is also damaged.

If the damage to the lung is very advanced and other therapeutic measures fail, a lung transplantation may be a necessary measure. The liver is the first organ affected by an Alpha-1-Antitrypsin deficiency. This leads to a disruption in the function of the protein alpha-1-antitrypsin.

The form of the protein is different from the healthy form. As a result, it accumulates in the liver cells and cannot be secreted properly. This results in a deficiency.

Newborns who are homozygous (i.e. they have two defective gene copies) show liver damage already in infancy. They are diagnosed with a prolonged neonatal icterus (jaundice = yellowing of the skin and sclera (white of the eyes)). If the disease does not appear until adulthood (approx.

10-20%), it is accompanied by chronic hepatitis (inflammation of the liver) and subsequent cirrhosis of the liver. Furthermore, the risk of developing liver cancer (hepatocellular carcinoma) is increased. Cirrhosis of the liver can lead to many complications for those affected. At an advanced stage, life expectancy is therefore also significantly reduced.