Deficiency of alfa1-anti-trypsin
Deficiency alpha 1 - anti-trypsin is the hereditary disease resulting from shortage of the proteinaceous enzyme preventing destructive effect of proteases on pulmonary fabric. At newborns it is shown by a syndrome of a holestaz, cirrhosis with characteristic symptomatology develops later. At adults the syndrome of bronchial obstruction, pulmonary emphysema come to light, is more rare - symptoms of a liver failure. The diagnosis is confirmed by determination of level alpha 1 - anti-trypsin in blood, genetic methods. Gepatoprotektor, bronchial spasmolytics, corticosteroids are appointed, replacement therapy is carried out. In hard cases transplantation of the damaged bodies is carried out.
Deficiency of alfa1-anti-trypsin
Deficiency of anti-protease (alpha 1 - anti-trypsin) develops as a result of a gene mutation and can proceed with primary damage of a liver at children or lungs at adults. 20% of all newborns with a shortcoming alpha 1 - anti-trypsin have a holestatichesky jaundice, subsequently at part of them cirrhosis comes to light. Deficiency of anti-protease serves as the reason of development of HOBL approximately at 2% all having this disease. However at many patients with a chronic obstructive pulmonary disease necessary genetic researches were not conducted. Prevalence of pathology is insufficiently studied. According to the available statistical data, deficiency of inhibitor of proteases meets at persons of Caucasian race more often. Incidence among inhabitants of Europe makes 1 on 1500–5000 people.
The reasons of deficiency alpha 1 - anti-trypsin
The gene mutation causing deficiency of anti-protease is inherited on autosomno-recessive or codominant type. The gene located on the 14th chromosome is responsible for production and release alpha 1 - anti-trypsin. This gene is polymorphic. There are its more than 500 various forms – alleles. Allocate the following main options of the damaged alleles, developing of pathology, responsible for various mechanisms:
- Scarce. At such mutation it is synthesized enough alpha 1 - anti-trypsin. Its ability to get through a cytoplasmatic membrane decreases. Secretion of enzyme to the blood course is broken, it arrives there in the minimum quantity. As a result anti-protease collects in cells of a liver, damaging them.
- Zero. Deficiency arises because of synthesis of defective and unstable anti-protease. Enzyme quickly breaks up even before its release in a blood-groove. Has no the damaging effect on cells of a liver. At such pathology pulmonary emphysema early develops. Zero alleles are the most rare mutation of the gene coding production of inhibitor of proteases.
- Dysfunctional. In this case the normal amount of inhibitor of proteases is produced and gets to blood. Properties of the enzyme are broken. Antiproteazny activity decreases or is completely lost. At some mutations enzyme gains other qualities, for example, similarity to anti-thrombin and ability to cause fatal bleeding.
The great influence on development of pulmonary pathology against the background of a shortcoming alpha 1 - anti-trypsin is exerted by smoking. Tobacco smoke increases activity of proteases and strengthens destruction of alveolar fabric. Deficiency of the protein protecting pulmonary fabric at smokers leads to developing of emphysema and HOBL much earlier, than at non-smoking with the same genetic defect.
The main function of antiproteazny enzyme is oppression of destructive action of a neytrofilny elastaza and some other proteases which are released at stressful situations. Its deficiency leads to decrease or lack of such protection of a pulmonary parenchyma. There is a gradual destruction of interalveolar partitions, there are emphysema and emphysematous option of HOBL. In the presence in a genotype of the person of scarce alleles enzyme in a large number collects in the place of its synthesis – hepatocytes. Excess of anti-protease damages hepatic cells and becomes the cause of cirrhosis and gepatotsellyulyarny cancer.
Displays of a disease differ at adult and children's age a little. The clinical picture directly depends on the nature of genetic defect. However both injuries of a liver, and violation of functions of respiratory system can meet in any age group. In pulmonology and hepatology deficiency alpha 1 - anti-trypsin is divided into the following options:
- With primary gepatobiliarny defeat. Arises at children more often. Symptoms of a disease appear in the first 4 months of life.
- With primary damage of lungs. Pathology comes to light at adults more often. This genetic disease is also defined at some children having bronchial asthma.
- With the combined defeat. Arises at heavy enzymatic insufficiency. The characteristic clinical symptomatology is observed in the early childhood.
Symptoms of deficiency alpha 1 - anti-trypsin
Essential deficiency of inhibitor of activity of proteolytic enzymes is shown by a holestatichesky syndrome already in the period of a neonatality. Integuments, skler of the baby get icteric coloring. In some cases the child has a vomiting, hemorrhagic rashes. Holestaz is usually allowed to 3-4 monthly age, progressing of process with formation of a liver failure is sometimes observed.
Signs of defeat of gepatobiliarny system can arise later at children's, youthful or adult age. The patient has pains in the right podreberye which are followed by nausea, sometimes vomiting, a meteorizm, a loss of appetite. Unmotivated weakness, increased fatigue disturbs. Integuments and visible mucous membranes turn yellow, the skin itch joins. Gradually complications, characteristic of cirrhosis, develop. Malfunction of respiratory system arise separately, or accompany a liver failure.
The main manifestation of damage of respiratory organs is short wind. In the beginning it arises at run, rise on a ladder it is higher than 3 floors, sports loadings. Eventually breath difficulty gradually progresses and disturbs the patient at insignificant activity and at rest. Unproductive cough, suffocation attacks with the complicated whistling exhalation belong to other symptoms of enzymatic insufficiency. Development of emphysema or HOBL, including, at the non-smoking and not working not harmful production patients is characteristic of shortage of enzyme early (till 40-45 summer age). Sometimes the disease debuts from developing of spontaneous pheumothorax.
Sometimes enzymatic insufficiency alpha 1 - anti-trypsin leads to development of a nekrotiziruyushchy pannikulit. The patient is disturbed by emergence of hypodermic knotty educations. Skin over them gets crimson and cyanotic coloring. Knots usually settle down on the top and lower extremities, but can be formed on any part of a human body. They are painful, have tendency to merge, suppurate and opened, leaving the sinking-down hems.
At primary defeat of respiratory system the disease is complicated by formation of pulmonary heart. Terms of emergence of this complication in many respects depend on the patient's genotype. At a considerable lack of enzyme pulmonary heart failure develops at children's, teenage age or at young adults. Less expressed deficiency at patients non-smoking, not subject to regular influence of aeropollyutant does not influence life expectancy. Defeat of gepatobiliarny system develops at a part of patients with scarce alleles. Tsirrotichesky changes of a liver arise approximately at 20% of children and 10% of adults with holestatichesky jaundice in the anamnesis. Quite often genetic defect becomes the reason of gepatotsellyulyarny cancer and a carcinoma of a lung.
Patients with alpha 1 - insufficiency are surveyed at the pulmonologist and the hepatologist. An important stage of diagnostic actions is collecting the anamnesis. At identification of HOBL or emphysema at persons 45 years are younger, bronkhoektaz of not clear etiology, existence of bronchial asthma, steady against therapy, idiopathic cirrhosis, a nekrotiziruyushchy pannikulit consultation of the geneticist is shown. Diseases of gepatobiliarny system and (or) a respiratory path at relatives of the patient are an indirect sign of shortage of anti-protease. Final confirmation of the diagnosis is carried out with the help:
- Laboratory analyses. Quantitative contents serumal alpha 1 - anti-trypsin is defined. When using a method of an immunoturbodimetriya normal values are in limits of 0,9 - 2 g/l, at measurement by means of a nefelometriya – 2-4 g/litre.
- Genetic researches. By means of phenotyping the molecular structure alpha 1 - anti-trypsin is defined. The enzyme isoforms confirming its insufficiency in a human body come to light. DNA testing helps to define type of a gene mutation at the patient and his relatives and to reveal degree of risk of transfer of a disease by inheritance.
- Tool diagnostics. On the roentgenogram of the patient increase in lightness of a pulmonary parenchyma mainly in basal departments decides on the pulmonary or combined form of a scarce state. Ultrasonography, KT or MRT of an abdominal cavity allows to reveal a gepatosplenomegaliya, symptoms of hepatic fibrosis.
- Liver biopsies. At a research of the received material by means of electronic microscopy granules alpha 1 - anti-trypsin in hepatocytes of a periportalny zone are defined. With age and in process of progressing of pathological process the sizes and quantity of granules increase.
Treatment of deficiency alpha 1 - anti-trypsin
The only etiotropny method of treatment of deficiency of anti-protease with severe defeat of a respiratory path is replacement therapy. Intravenous administration cleared human alpha 1 - anti-trypsin is carried out. Such treatment is not shown to patients with defeat of a gepatobiliarny zone as it does not prevent development of cirrhosis. Researches concerning stimulation of production of anti-protease are conducted by cells of a liver, gene therapy. To patients with pathology of respiratory organs pathogenetic therapy by bronchial spasmolytics and corticosteroids, the patient with hepatic manifestations – gepatoprotektor is appointed. At a heavy liver failure transplantation of a liver is possible, at pulmonary and warm – organokompleks change heart lungs.
Forecast and prevention
The forecast in many respects depends on genetic features of the patient and therapeutic actions. In the absence of treatment the forecast for any option of a course of disease adverse. Hepatic or respiratory heart failure early result in deep disability. Secondary prevention is of great importance for patients with pulmonary forms of a disease. They need to refuse smoking, work in harmful conditions is contraindicated. It is necessary to take root against flu and a pnevmokokkovy infection. Patients with gepatobiliarny manifestations need vaccination against viral hepatitises. The refusal of alcohol and observance of the diet sparing a liver is obligatory.