Introduction:
Alpha-1 antitrypsin deficiency is a hereditary disorder that is characterized by a decrease in levels of a protein known as alpha-1 antitrypsin found in the blood. The illnesses caused due to this deficiency are liver diseases (cirrhosis and hepatoma), chronic obstructive pulmonary disease, or skin conditions such as panniculitis. Alpha-1 antitrypsin deficiency is more common in individuals with Wegener’s granulomatosis or polyangiitis with granulomatosis. The deficiency of alpha-1 antitrypsin causes the protein-breaking substrates to attack various body tissues. This attack leads to several destructive lung, liver, or skin changes.
What Is Alpha-1 Antitrypsin?
It is a protein found in the blood which is released by specialized granules with the white blood cells (neutrophils or polymorphonuclear leukocytes) in response to any inflammation of infection. The deficiency of alpha-1 antitrypsin leads to a rapid imbalanced breakdown of protein. This phenomenon takes place, especially in the supporting elastic structure of the lungs.
What Are the Causes of Alpha-1 Antitrypsin Deficiency?
Alpha-1 antitrypsin deficiency is caused by a mutation in the SERPINA-1 gene, which is responsible for the production of alpha-1 antitrypsin protein. Generally, this protein is produced in the liver, then released in the blood, and protects the body from neutrophil elastase enzymes. Alpha-1 antitrypsin also shows anti-inflammatory effects independent of its anti-neutrophil elastase activity. Mutations of the SERPINA-1 gene result in the formation of an abnormal gene that gets trapped in the liver, leading to low serum levels of alpha-1 antitrypsin. This can cause lung breakdown by proteolytic enzymes. The accumulation of mutated alpha-1 antitrypsin can cause scarring in the skin.
Alpha-1 antitrypsin mutation is an inherited autosomal codominant condition. A codominant genetic disorder takes place when each inherited allele expresses some effect. In cases of codominant conditions, if two copies of abnormal genes are inherited from each parent, the risk of disease is very high compared to one abnormal gene inherited.
Which Population Is Affected by Alpha-1 Antitrypsin Deficiency?
The majority of cases of alpha-1 antitrypsin deficiency are seen in Americans of Northern or Central Europe. Most of the time, alpha-1 antitrypsin deficiency is unrecognized or underdiagnosed; only in approximately 10 % of total cases is the deficiency diagnosed. In this 10 % of cases, patients generally suffer from the chronic obstructive pulmonary disorder.
What Are the Symptoms of Alpha-1 Antitrypsin Deficiency?
As alpha-1 antitrypsin deficiency affects multiple organs such as the liver, lungs, and skin, the symptoms are categorized according to the organs:
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Lung Diseases: Alpha-1 antitrypsin deficiency-associated lung diseases are progressive, degenerative, and destructive changes in the lungs, mostly emphysema. Emphysema is a chronic, slowly progressive disorder that often causes shortness of breath, followed by other symptoms such as phlegm production, cough, and wheezing. Some individuals with alpha-1 antitrypsin deficiency never suffer from emphysema if they have never smoked.
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Liver Diseases: Alpha-1 antitrypsin deficiency-associated liver disease generally occurs during infancy, childhood, or adolescence. Symptoms in infancy include pallor of the skin for a long time, slightly elevated liver enzymes, dark urine, pale stools, and itching. Other symptoms of liver disease include bleeding, enlargement of the liver, accumulation of fluids within the abdominal cavity (ascites), and poor growth or failure to thrive. In addition, children and adolescents with this deficiency may possess liver dysfunctions, portal hypertension, fatigue, decreased appetite, enlargement of the liver, and swelling of the legs or abdomen. Alpha-1 antitrypsin deficiency-related liver diseases in adults are cirrhosis, portal hypertension, chronic active hepatitis, and hepatocellular carcinoma.
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Portal Hypertension: Increase in blood pressure within the vessels in the liver, which can cause bleeding from the esophagus or stomach, easy bruising, abnormally enlarged vessels in the stomach and esophagus, and fluid accumulation in the chest.
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Cirrhosis: The liver cannot properly dispose of the waste products of protein metabolism. It causes drowsiness and increased susceptibility to infections.
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Panniculitis: It is a rare skin disease manifested in cases of alpha-1 antitrypsin deficiency. It appears to affect both males and females equally at any age. The skin lesions in panniculitis begin as nodules that are tender, inflamed, red, and hardened. They occur beneath the skin and have irregular borders. The panniculitis generally affects the extremities or torso and is characterized by ulceration in addition to serum and blood drainage, accompanied by systemic symptom- fever.
How to Diagnose Alpha-1 Antitrypsin Deficiency?
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The diagnosis of alpha-1 antitrypsin deficiency depends on a low concentration of alpha-1 antitrypsin blood plasma in combination with a high-risk phenotype or genotype. Further testing of the sequence of alpha-1 antitrypsin genes is required to establish a confirmed diagnosis of alpha-1 antitrypsin deficiency.
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As alpha-1 antitrypsin generally goes unrecognized, it is important that all individuals with fixed airflow obstruction on spirometry should be tested. The first-degree relatives of individuals found with alpha-1 antitrypsin deficiency, such as parents, siblings, and children, should be examined. Individuals with unexplained liver diseases, bronchiectasis, or panniculitis should also be tested.
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Alpha-1 antitrypsin can be suspected in cases of emphysema in a younger individual, a non-smoker, or someone with a family history of emphysema.
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Alpha-1 antitrypsin deficiency should be checked in cases of liver diseases such as portal hypertension, hepatitis, jaundice, or hepatocellular carcinoma.
How to Treat Alpha-1 Antitrypsin Deficiency?
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In cases of emphysema associated with alpha-1 antitrypsin deficiency, the treatment includes administering standard medicines such as inhaled steroids, inhaled bronchodilators, anticholinergics, oxygen therapy, and antibiotics in cases of frequent respiratory infections. It is very important for individuals suffering from emphysema to avoid occupations exposed to lung irritants, smoking, or the use of non-medical aerosol sprays.
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The other treatment option for alpha-1 antitrypsin deficiency is augmentation therapy. It is a regular, long-term infusion of purified, pooled human plasma-derived alpha-1 antitrypsin in the veins of deficient individuals. Augmentation therapy helps to slow lung damage, but it does not affect alpha-1 antitrypsin-related liver diseases.
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In patients with end-stage lung disease, lung transplantation can be performed successfully.
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No specific treatment therapy for liver diseases associated with alpha-1 antitrypsin deficiency is available. However, some animal clinical trials show that drugs such as rapamycin or carbamazepine help to increase the liver’s ability to break down accumulated alpha-1 antitrypsin. Many more studies and investigations are still needed to confirm any therapy.
Conclusion:
Alpha-1 antitrypsin deficiency is a codominant autosomal disorder affecting the organs and lungs. Liver and skin. It occurs due to mutation of the gene SERPINA-1, which leads to the accumulation of alpha-1 antitrypsin protein in the liver instead of secreting it in blood plasma. The secretion of alpha-1 antitrypsin protein takes place during any infection or inflammation. The treatment of the deficiency depends on the symptoms caused in the affected organs. However, any standard treatment for liver diseases is still not found.
