Table of Contents
1. Introduction
Alpha 1-Antitryspin or α1AT is a glycoprotein composed of 52 kDa molecule which is produced in the liver and then released in to the blood. The primary function of α1AT in the human body is to restrict the activity of an enzyme called elastase. Elastase is used to decompose elastin which is a structural component of the lungs. If Alpha 1-Antitryspin does not control the behavior of elastase within the body then the lungs may get destructed intensively which causes respiratory complications such as emphysema, chronic obstructive pulmonary disease (among adults) and cirrhosis (among adults and children). Alpha 1-Antitryspin also inhibits a wide range of proteases other than elastase to protect various tissues that is why it is also known as Serum Tryspin Inhibitor and Alpha1 Proteinase Inhibitor. An abnormal form of Alpha 1-Antitryspin produced due to certain anomaly in the DNA, is not properly released to the blood stream from the liver. The abnormal form of Alpha 1-Antitryspin is called Z-mutation. If a person has acquired two Z genes then it is most likely that 85 percent of Alpha 1-Antitryspin produced in his body amass in to hepatocytes and compose in to aggregates. Hepatitis and cirrhosis may occur if the liver possesses the aggregates of the Z-form of the Alpha 1-Antitryspin. Z-form mutation generally does not put its carrier (patient) at the risk of lung diseases, since a small amount of Alpha 1-Antitryspin that flows in to the blood manages to inhibit the elastase and thus, saving the delicate Alveolar tissues in the lung parenchyma. Whereas as the other mutational forms of the Alpha 1-Antitryspin can stop the production of the gene or even produce an inactive form of the gene being secreted in to the blood which results in to the destruction of the lungs causing emphysema. These other mutant forms are not harmful for the liver as they do not gather in the liver. It is very rare that the deficiency of the Alpha 1-Antitryspin gene causes relapsing panniculitis.
2. Disease
Alpha 1-Antitryspin Deficiency is a congenital disorder defined by the reduced levels of serum of Alpha 1-Antityspin gene.
As discussed above that this deficiency of α1AT is the root cause of various lung and liver diseases. Smoking aggravates the risk of this deficiency. This disorder has no cure but it can be treated.
3. Background
C.B. Laurell and S. Erikksson in Malmo, Sweden were the first ones in the history to discover the congenital disorder of Alpha 1-Antitryspin Deficiency in 1963.It was then observed through the study of the specimens of human serum that in the existence of acute lung disease in the body, the Alpha 1 protein band was found to be either absent or deficient. Then it was established that almost 90 percent of the Alpha 1 protein band was actually a single protein with the power of restricting the activity of proteolytic enzyme known as tryspin that is the reason that the Alpha 1 protein was named as Alpha 1-Antitryspin. This research for carried forward by A. Janoff, P. Gross and many others, who then explained the behavior of Alpha 1-Antitryspin in the lungs. In the later years, it was found through experiments on the animals that the neutrophil elastase was the actual culprit responsible for damaging the lungs and thus, the major objective of Alpha 1-Antitryspin was to inhibit the function of elastase. By the early 1970's, means for diagnosing the Alpha 1-Antitryspin Deficiency were developed by measuring the levels and movement of abnormal molecules of Alpha 1-Antitrypsin serum through electrophoretic analysis which distinguish the inherited forms of α1AT from the serum on account of their electric charge. The genetic ground of α1AT Deficiency was suggested by G.L. Long et al through cloning and sequencing the α1AT forms and afterwards it was established by T. Nukiwa and others when they cloned and sequenced the Z form of the α1AT. Then J.E. Gadek and others exhibited through their work that emphysema occurs with the inability of Alpha 1-Antitryspin to inhibit neutrophil elastase from destroying the lung parenchyma due to its deficiency or absence. Finally, J.E. Gadek, M.D.Wewers and many others empirically concluded that Alpha 1-Antitryspin from a healthy person can be induced in to the patient having α1AT Deficiency.
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Doing so, increases the levels of α1AT in the lungs of the patient and thus, develops the anti neutrophil elastase defenses in his lungs. This research has resulted in the preparation of prolastin which is the purified form of α1AT for the treatment of Alpha 1-Antitryspin Deficiency in many developed Countries such as U.S. and European Countries.
4. Diagnosis
A test to determine the Alpha 1-Antitryspin level is taken to identify the cause of emphysema in its initial stage in a patient who does not show signs of evident risk factors such as smoking, exposure to dust, fumes or other substances that irritate lungs, etc.
Alpha 1-Antitryspin is also tested to determine the cause of jaundice continuing for long and other indications of dysfunctional liver. This is observed commonly among infants and young children and rarely, in patients of other ages.
Alpha 1-Antitryspin Phenotype Testing is done to find out whether the concentration of α1AT in the body is lower than the required level. It determines the amount and type of α1AT produced by the liver and correlates the result with the amount and type of α1ATproduced in a healthy person's body.
After the abnormality is confirmed by Alpha 1-Antitryspin level and phenotype testing then the DNA Genetic Testing is done to report the form of mutant found. The DNA test does not verify for all forms but the most common ones such as M, S and Z and also any other form that is commonly found in relation to a specific family or region. When the patient's Alpha 1-Antitryspin mutant variant has been found, the rest of his family may also be tested to identify their respective risks of getting lung or liver diseases. Also, the probability of their offspring carrying this genetic abnormality may be determined.
5. Symptoms
Alpha 1-Antitryspin testing is observed when an infant or a newly born suffers from jaundice that is persistent for a couple of weeks, spleen being enlarged and other indications of liver related problems. It may also be tested when a person below 40 years of age encounters breathlessness, bronchitis, persistent cough or shows other symptoms of emphysema. Alpha 1-Antitryspin testing is also recommended when you have a history of Alpha 1-Anitrypsin Deficiency in your family.
It is important to determine the amount and type of abnormal Alpha 1-Antitrypin being produced in the body. DNA testing identifies the existence of one or two abnormal genes which further indicates the production of α1AT being less and/or abnormal in the next generation of the patient since the abnormal gene is inherited by his children. The level of damage occurred to the liver or lungs of the patient may vary and is not absolutely dependent on the level of Alpha 1-Antitryspin Deficiency which means that two patients with the same copies of abnormal genes may experience different patterns in their disease(s).
Since Alpha 1-Antitrypsin is an acute phase reactant, it will be boosted with inflammatory conditions, infections and cancers. The levels of α1AT may also rise in pregnancy, oral contraceptives and stress. Normally, in such cases the patient is not tested for increased levels of α1AT. This may misleadingly express the level of α1AT as NORMAL in a patient with moderate α1AT Deficiency while he/she is experiencing another condition that raise the α1AT production in his body.
The level of Alpha 1-Antitryspin may also reduce in a patient with Neonatal Respiratory Distress Syndrome and cases such as kidney disease, malnutrition and cancer which cause serum proteins to decrease.
6. Treatment
The treatment of the Alpha 1-Antitryspin deficiency is to fulfill the shortage of α1AT by infusing the healthy α1AT in to the blood and thus, prevent the lungs from damaging. On the other hand there is no particular treatment available for the liver related diseases. It is not yet known that why the approach of production and/or secretion of Alpha 1-Antitryspin do not work in cases related to liver. However, it is probably linked to the accumulation of Z variant in the liver.
7. Disease Management
As mentioned earlier that the disorder of Alpha 1-Antitryspin Deficiency is an incurable disease but it can be treated and therefore, by properly avoiding the involved risk factors, the patient can live a healthy and normal life.
The following measures are to be adopted to avoid the risk factors.
- The patient should quit smoking as it is the biggest risk factor especially in case of lung diseases.
- The patient should take care of his personal hygiene to prevent infections. Hands should be washed regularly with warm water. Anti-bacterial soap should be used. Hands should be rubbed for at least 20 seconds and then rinsed thoroughly. Always dry your hands and apply moisturizer after every wash. If you are unable to wash your hands when required then at least clean them with anti-bacterial solution.
- The patient should strictly avoid dust and fumes.
- The patient should take several small meals to avoid wheezing after eating.
- The patient should also take food that is low in carbohydrates so that low carbon dioxide is produced.
- All fruits and vegetables should be washed before use.
- Separate cutting boards should be used for raw food and cooked food and they should also be washed properly after use.
- Meat and eggs should be cooked until well done.
- Take food enriched with proteins and amino acids.
- Include Vitamins and Minerals in your diet.
- Exercise regularly.
- Don't take stress.
- Sleep tight for 6-8 hrs at night.
- Visit your Doctor regularly.
- Take the prescribed medicines regularly and follow your Doctor's instructions.