Alpha-1 antitrypsin deficiency is a hereditary disease characterized by defective synthesis of alpha-1 antitrypsin in the liver, causing damage to the liver and lungs. Alpha-1-antitrypsin deficiency represents one of the causes of respiratory diseases that are often not recognized or recognized late.
What is alpha-1-antitrypsin deficiency?
Alpha-1 antitrypsin deficiency is a hereditary disorder that has a lasting negative effect on the lungs and liver. Alpha-1 antitrypsin deficiency is a hereditary disease that has a lasting negative effect on the lungs and liver. Since the gene responsible for the disease can be subject to various mutations, different clinical pictures can emerge. These range from mild forms of the disease, which may be associated with no symptoms, to severe forms of alpha-1-antitrypsin deficiency, which may result in liver cirrhosis and emphysema. In addition, the form of the disease is determined by whether the genetic defect responsible for alpha-1 antitrypsin deficiency was passed on by only one parent (heterozygous, mild form) or by both parents (homozygous, severe form).
Causes
Alpha-1 antitrypsin deficiency results from a gene defect in chromosome 14, which is responsible for the synthesis of alpha-1 antitrypsin and produces defective alpha-1 antitrypsin when the disease is present. Alpha-1-antitrypsin is a protein that inhibits protein-degrading enzymes such as elastase (known as proteases). In a healthy person, there is a balance between alpha-1-antitrypsin and the body’s own proteases. If the lungs are irritated by a bacterial infection or dust, elastase is released, which breaks down the proteins in the harmful substances. However, elastase cannot differentiate between endogenous and foreign proteins and also attacks lung tissue if it is not inhibited by alpha-1-antitrypsin. In alpha-1-antitrypsin deficiency, a greatly reduced amount of “error-free” alpha-1-antitrypsin is present in the blood, the regulatory mechanism does not take effect, and lung tissue is damaged. In addition, the nonfunctional alpha-1-antitrypsin is deposited in the liver and leads to the liver damage typical of alpha-1-antitrypsin deficiency.
Symptoms, complaints, and signs
Alpha-1-antitrypsin deficiency is typically associated with chronic obstructive pulmonary disease. This clinical picture is manifested by a number of symptoms and changes. Initially, there is shortness of breath, which occurs primarily during physical exertion. This is accompanied by coughing, heavy expectoration and wheezing or whistling breathing. Damage to the lung tissue can lead to pulmonary hyperinflation, which causes a dry, irritating cough and pain. Due to the lack of oxygen in the blood, the skin turns blue. Furthermore, chronic obstructive pulmonary disease is manifested by recurrent respiratory infections, for example chronic bronchitis or inflammation of the upper throat. The above-mentioned symptoms usually appear between the ages of 30 and 40, although alpha-1-antitrypsin deficiency may exist for a long time before that. Even before that, liver symptoms may occur. If the production of alpha-1-antitrypsin can no longer take place as usual, altered molecules accumulate in the liver cells. This can lead, among other things, to chronic hepatitis and cirrhosis of the liver – both of which often become apparent in childhood and adolescence. The typical symptoms are a yellowing of the skin, sunken eye sockets and sometimes pain in the upper abdomen. As the disease progresses, physical performance decreases considerably.
Diagnosis and course
Alpha-1 antitrypsin deficiency is diagnosed by blood analysis. If the alpha-1 antitrypsin level is significantly below normal, this indicates alpha-1 antitrypsin deficiency. The diagnosis can be confirmed by taking tissue from the liver (liver biopsy) or by genetic analysis.While the typical liver symptoms of alpha-1-antitrypsin deficiency such as chronic hepatitis, liver cirrhosis and icterus (yellowing of the skin) can already be observed in childhood, the lungs usually do not develop the signs of disease characteristic of alpha-1-antitrypsin deficiency, such as chronic bronchitis, often in combination with emphysema, shortness of breath, irritable cough and cyanosis (blue discoloration of the skin), until between the ages of thirty and forty. Approximately one-fifth of affected individuals also exhibit bronchial hyperreactivity (airway hyperresponsiveness). Alpha-1 antitrypsin deficiency is characterized by a progressive, potentially lethal (fatal) course of disease.
Complications
Alpha-1 antitrypsin deficiency can result in several complications. Alpha-1-antitrypsin inhibits protein-degrading enzymes, which means that in the case of a deficiency, the degrading enzymes are not inhibited, which is why lung tissue degradation can occur, especially in the lungs. The affected person breathes less easily and thus suffers from shortness of breath. The most common consequence is chronic obstructive pulmonary disease (COPD). This is characterized by a strong decrease in quality of life, but also in life expectancy. In addition, this leads to overinflation of the alveoli (emphysema). This further aggravates the shortness of breath and the irritating cough, and the affected person may suffer from oxygen deficiency (cyanosis). In addition, the pressure in the pulmonary vessels is increased, so that the right heart must exert greater pressure to stop against the resistance. This can end in weakness (right heart failure), which is characterized by a sharp decrease in performance and fatigue. In the liver, the deficiency of alpha-1-antitrypsin also leads to significant damage, which can even lead to liver cirrhosis. This severely limits the synthesis capacity of the liver, which is why fewer proteins are produced. A disturbance of coagulation can be the consequence here, but a more frequent occurrence of edema can also be observed in this case.
When should one go to the doctor?
Since alpha-1 antitrypsin deficiency can cause damage to the lungs and liver in particular, medical treatment must definitely be sought for this disease. The disease will not heal by itself, it needs treatment, otherwise the affected person may die from it in the worst case. Since jaundice usually occurs, the affected person should see a doctor or go directly to the hospital at the first signs. In most cases, a general practitioner can also be visited here, who will refer the patient to a specialist. In addition, coughing and shortness of breath are also symptoms of alpha-1-antitrypsin deficiency and should be examined by a physician. The lack of oxygen can cause a blue discoloration of the skin. In the long run, organs and extremities can be irreversibly damaged. For this reason, a doctor should also be consulted immediately in the event of blue discoloration of the skin. In many cases, the patient’s resilience and performance also decreases significantly, which is also one of the common symptoms of alpha-1 antitrypsin deficiency.
Treatment and therapy
Because alpha-1-antitrypsin deficiency is genetic, no causal (cause-fighting) therapy exists. Alpha-1-antitrypsin deficiency is usually treated by replacement therapy (substitution therapy) in cases of mild disease expression and concomitant impaired lung function, in which intravenous alpha-1-antitrypsin synthesized by genetic engineering or from blood plasma is injected. The aim of the therapy is to slow down the decline in lung function. In this context, nicotine abstinence (avoidance of active and passive smoking) is fundamental for the success of the treatment, since tobacco smoke additionally damages the alveoli and reduces the effect of the replacement therapy. At the same time, the corresponding secondary and concomitant diseases of alpha-1-antitrypsin deficiency that have already occurred are treated. Furthermore, respiratory therapy and appropriate infection prophylaxis (pneumococcal and influenza vaccination) should take place. In some patients with alpha-1-antitrypsin deficiency, studies have shown that therapy with glucocorticoids (including cortisone inhalers) can have a positive effect if lung function is impaired.In the advanced course of alpha-1-antitrypsin deficiency, surgical therapy measures such as removal of the overinflated lung areas (lung volume reduction), liver or lung transplantation become necessary. The average life expectancy in alpha-1 antitrypsin deficiency is 60 to 68 years, although nicotine use significantly decreases this (48 to 52 years).
Outlook and prognosis
In general, alpha-1 antitrypsin deficiency results in various damages and complaints to the lungs and liver. In many cases, the complaints in the lungs are recognized relatively late, so that early treatment of this disease is usually not possible. Those affected primarily suffer from jaundice, which is triggered by the complaints in the liver. In addition, damage to the lungs can lead to a severe cough and respiratory distress. Due to the shortness of breath, organs and the brain may not be supplied with sufficient oxygen. Likewise, the undersupply of oxygen leads to severe fatigue and exhaustion. As a result, those affected can hardly perform any physical work and are therefore significantly restricted in their daily lives. The quality of life is reduced by the alpha-1-antitrypsin deficiency. It is not possible to treat alpha-1-antitrypsin deficiency causally. Treatment is therefore purely symptomatic and is aimed at treating the individual complaints. The affected person must therefore abstain from cigarettes and alcohol in particular. Life expectancy is significantly reduced by alpha-1 antitrypsin deficiency.
Prevention
Because alpha-1 antitrypsin deficiency is hereditary, no direct preventive measures exist. However, a severe course of the disease can be prevented by following specific behavioral rules. These include abstaining from cigarettes, limiting alcohol consumption, avoiding pollutants that impair lung function (stoves, high ozone levels, dust particles), and taking preventive measures against respiratory diseases (pneumococcal vaccination, influenza vaccination). Learning the appropriate breathing technique as part of physiotherapy measures and lung sports can also minimize the respiratory symptoms caused by alpha-1-antitrypsin deficiency and thus raise the quality of life.
Follow-up
In alpha-1 antitrypsin deficiency, the focus is on symptomatic treatment of the disease itself, since causal and etiologic therapy is not possible. Because alpha-1-antitrypsin deficiency is a congenital disease, genetic counseling should be performed if there is an existing desire to have children in order to prevent the recurrence of this disease in the children. In many cases, the disease leads to further symptoms and diseases of the respiratory tract and liver, so these organs should be examined regularly to avoid complications. The affected person should avoid smoking in any case, while in general a healthy lifestyle with a healthy diet has a positive effect on the further course of the disease. Furthermore, it is also necessary to take medication in order to permanently alleviate the symptoms. It is important to ensure that the medication is taken regularly, and the interactions with other medications should also be taken into account. The life expectancy of the patient is significantly reduced by the alpha-1-antitrypsin deficiency. It is not uncommon for psychological upsets or depression to occur as a result of the deficiency. In this case, discussions with friends or family can have a positive effect on the further course of the disease. Contact with others affected by alpha-1 antitrypsin deficiency is also useful and can lead to an exchange of information.
What you can do yourself
The rare hereditary disease alpha-1-antitrypsin deficiency is present from birth but is often not recognized because the first symptoms usually do not appear until adulthood. As a result, early, helpful medical treatments and targeted self-help measures usually fail to materialize. Early detection of the enzyme deficiency could also help a number of self-help measures to be more effective. Even if there is already damage to the lung tissue when the disease is diagnosed, light endurance and interval training three to five times a week within the existing possibilities is important. This strengthens the alveoli that are still intact. Targeted training of the respiratory muscles is helpful in supporting breathing.Special attention should be paid to a diet rich in vitamins and enzymes, which can be composed of purely vegetable products as well as including animal products. It is particularly important to ensure an adequate supply of the fat-soluble [[vitamins A|Vitamins A, D and E, as well as the powerful antioxidant vitamin C. Vitamin E in particular protects the cell membranes so that the immune system can act less aggressively on the lung tissue. As a purely precautionary measure, those affected should avoid contact with people who are obviously suffering from a cold or any other bacterial or viral illness as far as possible, in order to prevent infection if possible. Compliance with a strict smoking ban is considered an important precondition for the effectiveness of all measures.
