Alpha-1 antitrypsin deficiency
* Introduction
* Signs and symptoms
* Diagnosis
* Treatment
Alpha-1 antitrypsin deficiency is a lack of affection ereditaracauzata liver protein alpha-1 antitrypsin, which blocks the function of enzymes forcing destructive emphysema, liver damage and sometimes skin. Infants with this disorder shows hepatomegaly and cholestatic jaundice in the first week of life. Cirrhosis may occur in childhood or adolescence. Adults with asthma emphysema shows signs and symptoms including: coughing, wheezing, dyspnea and prolonged expiration.
Alpha-1 antitrypsin deficiency is suspected in smokers who develop emphysema before age 45 and who develop emphysema from smoking at any age. In patients with unexplained cirrhosis in this paniculitei and infants with prolonged jaundice.
Positive diagnosis comes after measuring the level of serum alpha-1 antitrypsin. Persons who do not smoke and disease have a normal life expectancy and only a slight change in the lung and liver functions. Most common cause of death is emphysema followed by liver cirrhosis and carcinoma.
Treatment consists of administration of purified human alpha-1 antitrypsin. Since pulmonary emphysema cause permanent structural changes, therapy can improve lung damage but stops progression. Treatment is very expensive and is reserved for non-smokers when both alleles are inherited abnormal gene and have mild to moderate symptoms. It is indicated for patients with severe disease or with one or both normal alleles. Treatment of liver disease is supportive. Enzyme replacement does not help because the disease is caused by its abnormal processing than the lack thereof. Treatment of panniculitis is still under study, have tried steroids, tetracyclines and antimalarials.
Pathogenesis
Alpha-1 antitrypsin is an inhibitor of a antiproteaza neutrophilic elastase. Its major function is to protect the lungs from protease-mediated tissue damage. Predominant amount of alpha-1 antitrypsin is synthesized in the liver and monocytes and is passively diffused pulmonary circulation. A secondary quantity is produced by alveolar macrophages and epithelial cells. Inheritance of allelic variants of the altered gene that encodes this enzyme determine its conformation change leading to polymerization and retention in hepatocytes. Cholestatic jaundice, hepatic accumulation lead to 10-20% of patients, the rest can degrade abnormal protein.
In the lung alpha-1 antitrypsin deficient neutrophilic elastase activity increases facilitating tissue destruction leading to emphysema, especially smokers, cigarette smoke also increased elastase activity.
Other organs affected are the skin-paniculata, severe hemorrhage of blood vessels (through a mutation that converts the alpha-1 antitrypsin inhibits clotting), aneurysm formation, ulcerative colitis, neutrophilic anticitoplasma Action and glomerular disease.
Causes
Alpha-1 antitrypsin deficiency is a genetic disorder that is inherited from parents. Normal every child receives two alleles for each gene, one from mother and a father. There are many variants of this gene but the most dangerous disease development are S and Z. People who have the disease can be SZ or ZZ. They will forward one of the two alleles of each child. Alpha-1-bearer is a person who has a normal allele and a modified S M sua Z. A quarter of the world population is a carrier. Their parents are also carriers and do not develop the disease. Bearers of alpha-1 almost never develop the disease. If it was precipitated by damage triggered by viral liver by alcohol or overeat.
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