English: alpha1-antitrypsin deficiency
Alpha-1-antitrypsin deficiency means, as the name suggests, the lack of the protein alpha-1-antitrypsin, which is formed in the lungs and liver. So it is a metabolic disorder.
This condition is inherited in an autosomal recessive manner. It occurs with a frequency of 1: 1000 to 1: 2500 in the population.
The cause of the alpha-1 antitrypsin deficiency lies in a fault in inheritance.
The deficiency of the protein alpha-1-antitrypsin is inherited in an autosomal recessive manner. This means that the disease is inherited regardless of gender and only really breaks out if there are two defective gene copies. Both parents must either be ill or act as carriers of the genetic information. Only a single gene that carries the incorrect information cannot cause any damage. The defect is on chromosome 14. On this chromosome is the gene that is used in healthy individuals for synthesis (Manufacturing) of alpha-1 antitrypsin is responsible.
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Alpha-1-antitrypsin is a protein produced by the body (protein), which is mainly produced in the cells of the liver.
It has the task of inhibiting protein-splitting enzymes. An alpha-1-antitrypsin deficiency now leads to 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 leukocyte elastase enzyme. This namely breaks down the elastase in the wall of the alveoli.
Since the production of alpha-1-antitrypsin mainly takes place in the lungs and liver, damage and impairments also occur here. The breakdown of the body's own tissue also takes place there.
There is a very wide variability in the form. In people with severe lung damage, liver involvement is surprisingly rare and vice versa. The age distribution is also quite different. While some have end-stage lung diseases in the third to fifth decade of life, others do not have any damage to the lungs by the age of 30.
Sometimes patients with alpha-1 antitrypsin deficiency have inflammation in the subcutaneous fat. This is demarcated and reddish. It's called panniculitis. There are other causes of this inflammation as well. The exact mechanism of its formation is not yet known. This localized inflammation can be very persistent and painful.
Another symptom on the skin is the blue color (cyanosis). This is caused by insufficient 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, so it is 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. In the event of a deficiency in this alpha-1 antitrypsin, important components of the lungs are broken down, resulting in constant destruction of the lung tissue.
An alpha-1 antitrypsin deficiency causes emphysema in the lungs. Pulmonary emphysema is an overinflation of the lungs. This occurs due to the inflammatory changes in the lung structure. The walls of the alveoli are no longer stable enough and are destroyed by enzymatic degradation. This creates large cavities in the lungs from which inhaled air can no longer escape. That is why one speaks of overinflation of the lungs.
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Chronic obstructive pulmonary disease (COPD) also 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.
The feeling of shortness of breath is also typical in the advanced stage. This can also have consequences for the heart, so that it is also damaged. In the case of very advanced lung damage and failure of other therapeutic measures, a lung transplant may be a necessary measure.
$config[ads_text2] not foundRead more about: End-stage COPD
The liver is the first organ to be affected by alpha-1 antitrypsin deficiency. The alpha-1-antitrypsin protein is impaired. The form of the protein is different from the healthy form. This leads to the fact that it accumulates in the liver cells and cannot be released properly. This creates a defect.
In newborns who are homozygous (i.e. they have two defective gene copies) from the disease, the liver is already damaged in infancy. They are diagnosed with prolonged neonatal jaundice (jaundice = yellowing of the skin and sclera (white of the eyes)).
If the disease only appears in adulthood (approx. 10-20%) it is accompanied by chronic hepatitis (inflammation of the liver) and subsequent liver cirrhosis.
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.
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Read more on the topic: Cirrhosis of the liver
The diagnosis of alpha-1 antitrypsin deficiency is based on a blood sample and laboratory examination. The patient's blood is examined for its individual components (here especially for the protein composition).
There is an almost complete absence of alpha-1 proteins. Elevated liver enzymes can also be found in the blood. The ultrasound shows an enlarged liver (med .: hepatomegaly).
A liver biopsy (tissue samples from the liver) also shows characteristic deposits.
Since the enzyme alpha-1-antitrypsin is not formed correctly in the liver, the incorrectly formed enzyme is deposited in the liver cells and thereby destroys them.
This increases the liver parenchyma markers such as GOT, GPT, and glutamate dehydrogenase (GLDH). The alkaline phosphatase is also often increased. With advanced liver cirrhosis, other parameters are also affected. Typical would be a decreased albumin, a decreased cholesterol esterase (CHE) and decreased coagulation factors, as well as an increased ammonia value.
Read more about this: Elevated liver values
There are two tests that really prove this condition. That is the serum electrophoresis and the genetic test.
In serum electrophoresis, the total concentration of serum proteins from the blood and the fractionation of these are determined. It is a laboratory diagnostic test. In general, protein concentrations are shown as a line with peaks in a coordinate system. There are 5 peaks, the second peak of this curve shows the content of alpha-1 globulins, which includes alpha-1 antitrypsin. If there is a deficiency, this peak is correspondingly smaller.
The genetic test is carried out, for example, in a human genetic laboratory. To do this, the patient's DNA is examined for mutations in the associated gene (see inheritance).
All other tests, such as a lung function test, a chest X-ray, or a liver ultrasound, can explain symptoms of the disease, but not the cause.
This article might also interest you: The Alpha-1 Antitrypsin Test.
The deficiency of alpha-1-antitrypsin can now be easily remedied by giving the protein intravenously.
In addition, however, the organ diseases must be treated (especially liver cirrhosis) and any damage that has already occurred must be repaired. In extreme cases, however, a liver or lung transplant must be considered.
The administration of alpha-1-antitrypsin has the following side effects:
Gene therapy is in prospect in the future.
The alpha-1 antitrypsin deficiency is due to various mutations in the genes. It is a rare, inheritable disease that occurs with a frequency of about 1: 2000 to 1: 5000.
Those affected can suffer from a mild or severe form of the disease, which is associated with various secondary diseases and complications.The life expectancy, especially of those patients who are affected by a severe form, is reduced compared to the healthy population. Life expectancy is estimated at around 60 to 68 years.
However, this only applies to those affected who carry out consistent therapy and adhere to a strict smoking ban. Alcohol consumption should also be avoided, as it increases the likelihood of liver disease occurring.
Life expectancy is heavily dependent on the secondary diseases and the preserved organ function of the lungs and liver. In the event of organ failure or severely restricted function, the last resort is usually only an organ transplant, which is also associated with a reduced life expectancy and the risk of further secondary diseases.
There is no actual prophylaxis because the disease is inherited. Those affected should not smoke, as it makes it more difficult and puts even more strain on the lungs. Alcohol should also be avoided due to the strain on the liver.
Alpha-1 antitrypsin deficiency is inheritable. The corresponding gene sequence of this enzyme is on the 14th chromosome.
If the gene sequence contains a mutation, the sequence can no longer be read correctly and the enzyme is incorrectly formed. The severity of the disease is therefore variable. The mutation is inherited, i.e. passed on from the mother or father. A patient is fully developed when a defect is inherited from the paternal as well as the maternal side. The extent to which the patient is affected depends on genetics, but also on external factors such as smoking.
Alpha-1 antitrypsin deficiency is a hereditary metabolic disease, which mainly results in changes in lung tissue. The frequency of the disease is 1: 2000. Due to the lack of this enzyme, there is no inhibitory effect on protein-splitting enzymes.
Due to this deficiency, your own lung tissue is broken down or digested.
Pulmonary emphysema (including coughing and shortness of breath) occurs and, with additional liver involvement (10-20%), hepatitis (jaundice). The diagnosis is made using a blood analysis. Therapy is through substitution therapy, i.e. alpha-1-antitrypsin is administered artificially. The missing protein is given intravenously (through the vein). There is no prophylaxis.
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