Alfa-1-antitrypsin deficiency: symptoms, causes, diagnosis and treatment

Deficiency of Alfa-1-antitrypsin is a disease of an innate nature, transmitted at the genetic level at conception of the child. Symptoms begin to manifest from the first days of the baby's life. With the passage of time, clinical signs become more diverse, and the patient's condition gradually worsens. In most patients, doctors diagnose a pulmonary form of pathology. Only 12% of patients have symptoms of liver tissue damage. Modern medicine does not have specific means for treating the disease. Therefore, the main measures should be aimed at slowing the course of the disease.

What is Alfa-1-antitrypsin?

This protein, for the production of which corresponds to liver cells. From there, it enters the bloodstream and then is transported to the lungs. What is this protein for? Its main function is to protect the lung tissue from damage by other types of proteins - enzymes. These substances are necessary for the full functioning and development of the whole organism. For example, proteases are responsible for removing bacteria from the lungs, helping to fight infectious processes. Released in large quantities, they also contribute to protecting the alveoli from exposure to tobacco smoke. The activity of these enzymes should be balanced. With the deviation of indicators in the direction of increase, the lung elements begin to melt. Alfa-1-antitrypsin allows to regulate the activity of protease enzymes.

How is the deficit formed?

In one cell nucleus contains only 46 chromosomes. All of them are divided into 23 pairs. In each pair, one chromosome is inherited from the father, the other from the mother. It is a threadlike structure. In turn, each gene consists of a certain sequence of deoxyribonucleic acid and occupies a certain place in the chromosome. He also controls a particular function or performs his own work in the body. DNA forms the genetic material of a person.

Insufficiency of Alfa-1-antitrypsin is accompanied by damage to the gene in chromosome No. 14. When duplicating the protein is not produced in the required quantity, a deficit is formed. This substance settles in the liver and does not enter the lung tissue. Such a violation entails damage to the alveoli and the development of emphysema. Residual protein in the liver contributes to the formation of scar tissue. As a result, hepatic insufficiency develops .

Mechanism of disease transmission

For the first time the pathology characterizing the lack of Alfa-1-antitrypsin was described in 1963 by the Danish doctor Sten Erikson. Today, it is rarely diagnosed. However, the number of patients increases exponentially. Why? It's all about the genetic nature of pathology. The disease is inherited when both parents are carriers of an abnormal gene. According to statistical data, 1 person out of 25 is diagnosed with a similar defect. If two partners of the opposite sex with a damaged gene decide to conceive a baby, an unhealthy child will most likely appear. To date, for every 5 thousand people there is only one with the development of a full-fledged clinical picture. Only a few decades ago these figures were several times lower. For 20 thousand people there was only one with a defective gene. Such statistical data fully illustrate the extent of the spread of pathology.

Symptoms and first manifestations of the disease

The clinical picture of the pathological process is largely determined by its form and degree of injury. In most people, the symptoms of the disease do not make themselves felt for decades. In others, on the contrary, pathology is rapidly progressing. This process is affected by the patient's living conditions and lifestyle.

Pulmonary manifestations of the disease occur most often. For smokers, they appear after 20 years. In patients who adhere to a healthy lifestyle, this threshold is almost halved (40-45 years). First there is shortness of breath after intense physical exertion. It gradually leads to a worsening of the respiratory process. Then cough with sputum is attached. This disease is characterized by frequent inflammatory diseases of the upper respiratory tract.

Deficiency of Alpha-1-antitrypsin in children, more precisely its hepatic symptoms, arise from the first days of life. They manifest themselves in the form of hepatitis of unclear etiology, jaundice of the skin. By 14-16 years, most clinical cases are resolved in the direction of minimizing liver symptoms. Some adolescents have episodic pains in the right hypochondrium region. The appearance of liver symptoms in adults is dangerous by the development of complications. A similar picture characterizes scar tissue organ, which subsequently leads to severe cirrhosis and death of a person.

Differential diagnostics

Protein Alfa-1-antitrypsin plays an important role in the functioning of the whole organism. Its insufficiency is accompanied by serious complications, and sometimes leads to the death of a person. The group at increased risk of pathology includes:

• Smoking people with emphysema that appeared before the age of 45;
• Patients with panniculitis;
• Non-smokers who have been diagnosed with emphysema after 45 years;
• Newborn babies with severe jaundice or increased content of liver enzymes;
• Patients with bronchiectasis of unclear etiology.

To conduct differential diagnosis, the patient must donate blood to Alfa-1-antitrypsin. If the analysis confirms protein deficiency, each member of the patient's family needs to undergo a full medical examination for the detection of a defective gene. All other diagnostic measures are aimed at determining the degree of tissue damage. Periodically it is necessary to undergo examination for:

• Assessment of the vital volume of the lungs and the frequency of respiratory movements;
• Determination of spirometry parameters;
• Delivery of blood tests for liver tests.

Principles of treatment

Emphysema provokes irreversible changes. Therefore any applied therapy does not allow to restore the structure of the lungs or improve their work, but it can stop the progression of the disease. The treatment is quite expensive and is recommended only to non-smokers who have a mildly abnormal organ function. It is indicated if, in the analysis, Alfa-1-antitrypsin is within the lower bound.

Refusal to smoke, use of bronchodilators are important components of therapy. Experimental treatment using phenylbutyric acid, which allows reversing the formation of proteins in hepatocytes, is still under development. Many patients under the age of 60 doctors offer lung transplantation. Information on the benefits of an operation to reduce the volume of an organ with emphysema is highly controversial.

Treatment for liver damage is symptomatic. Substitution of enzymes in most cases is ineffective, because the disease is caused by a pathological process. Patients with hepatic insufficiency are shown organ transplantation. For treatment of panniculitis, corticosteroids and tetracyclines are used.

Forecast

What to expect for patients diagnosed with Alfa-1-Antitrypsin Deficiency? Treatment of this disease involves only alleviating the patient's condition. Completely overcome this pathology is not possible. The prognosis depends on the degree of organ damage. In particularly serious cases, it is unfavorable. A person dies of emphysema or cirrhosis.

Scientists from all over the world continue to actively study this disease, to seek a universal medicine. For example, in the US and some European countries, patients are asked to submit a disease-confirming analysis before initiating an experimental treatment. Alpha-1-antitrypsin, obtained from plasma of absolutely healthy people, is injected intravenously. Treatment is carried out according to specially developed schemes. Similar procedures are repeated several times a month. This method of treatment is costly and preventive. In addition, it is not suitable for patients with hepatic manifestations of the disease, when the pathological process involves not the lungs. In such situations, therapy is reduced to eliminating the symptoms of the disease.

Preventive measures

Specific methods of disease prevention, modern medicine can not offer. Doctors recommend couples planning to conceive a child, attend genetics counseling. This is especially true for parents, one of whom already has a defective gene.

Let's sum up the results

The disease, characterized by a shortage of pulmonary protease and the accumulation of pathological antitrypsin in the liver, is relatively rare. However, every year the number of patients with symptoms is increasing exponentially. Unfortunately, it is not possible to prevent its development.