ISSN 2230-9446 2011 I Vol.

2 I Issue 4 I 1-3
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REVIEW ARTICLE

Alpha-1 Antitrypsin: A Review

Ali Shah SM1, Asif HM1, Akram M2 (), Ahmed Khalil1, Ayaz Sultan2, Ur Rehman Riaz1
1College 2Shifa

of Conventional Medicine, Islamia University Bahawalpur, Pakistan.

ul Mulk Memorial Hospital, Faculty of Eastern Medicine, Hamdard University Karachi, Pakistan.

() Corresponding author; Email: makram_0451@hotmail.com

Abstract
Alpha 1 antitrypsin is a protein which is produced in liver, secreted in blood and ultimately reaches to lungs. It protects the alveoli against the injurious effect of neutrophil elastase. In this review article, introduction, epidemiology, pathophysiology, signs and symptoms, diagnosis, treatment of alpha 1 antitrypsin deficiency have been eloborated. Keywords: Alpha 1 antitrypsin, Neutrophil elastase, Protein.
SJPH 2011, Received on: 25.01.2011; Revised on: 07.02.2011; Accepted on: 15.02.2011

Introduction
Alpha-1 antitrypsin deficiency (also referred to as Alpha-1 or AATD) is caused by mutations in the SERPINA1 gene on chromosome 14. This gene codes for an enzyme called alpha-1 antitrypsin. It is produced in the liver and released into the blood, ultimately to protect the lungs from attack by an enzyme called neutrophil elastase. Neutrophil elastase is produced by white blood cells in response to infection or irritants to digest damaged tissue in the lungs. When SERPINA1 is mutated the abnormal alpha-1 antitrypsin protein gets stuck in the liver and is unable to pass into the bloodstream. Without protection from this protein, the lungs are left vulnerable to attack by neutrophil elastase. The accumulation of alpha-1 antitrypsin can also damage the liver [1,2]. Epidemiology Alpha-1 is more prevalent among caucasians, affecting 1 in 2,500. In fact, it is one of the most common autosomal recessive disorders among this population. This disorder is hard to spot because people are often not diagnosed until middle adulthood. It often is estimated that 95% of people who have alpha-1
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antitrypsin deficiency have never been diagnosed. Patients with this disorder need to stay away from tobacco, because smoking worsens the disease. Smoke damages the lungs by increasing secretion of neutrophil elastase, and by inhibiting alpha-1 antitrypsin [3,4].

Fig. 1: Human lungs and alveoli

Pathophysiology The genetic defect in AATD changes the configuration of the alpha1-antitrypsin molecule that prevents its release from hepatocytes [5]. As a result, serum levels of alpha1-antitrypsin are decreased and alpha1antitrypsin level also decreases in alveoli, where the alpha1-antitrypsin molecule
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normally would serve as protection against antiproteases. The resulting protease excess in alveoli destroys alveolar walls and causes emphysema [6]. The accumulation of excess alpha1-antitrypsin in hepatocytes can also lead to destruction of these cells and ultimately, clinical liver disease [1]. Alpha-1 Antitrypsin Deficiency: Autosomal Recessive Disorder An

Alpha-1 is an autosomal recessive disorder [7]. A child must inherit one abnormal gene from each parent to develop the disease [4]. If a child inherits a normal gene from one parent and an abnormal gene from the other, he or she will only be a carrier. Carriers produce lower-than-normal levels of the alpha-1 antitrypsin protein, but they still have enough of it to protect their lungs. Signs and Symptoms Symptoms of AATD include shortness of breath, wheezing, rhonchi, and rales. The patient's symptoms may resemble recurrent respiratory infections or asthma that does not respond to treatment. Individuals with alpha 1 antitrypsin may develop emphysema during their thirties or forties even without a history of significant smoking, though smoking greatly increases the risk for emphysema [8]. A1AD also causes impaired liver function in some patients and may lead to cirrhosis and liver failure (15%). It is a leading cause of liver transplantation in newborns. Diagnosis AATD is diagnosed through testing of a blood sample, when a person is suspected of having

AATD. For example, AATD may be suspected when a physical examination reveals a barrelshaped chest, or, when listening to the chest with a stethoscope, wheezing, crackles or decreased breath sounds are heard. Testing for AATD, using a blood sample from the individual, is simple, quick and highly accurate. Three types of tests are usually done on the blood sample: (a) Alpha-1 genotyping, which examines a person's genes and determines their genotype; (b) Alpha-1 antitrypsin PI type of phenotype test, which determines the type of AAT protein that a person has; and (c) Alpha-1 antitrypsin level test, which determines the amount of AAT in a person's blood. Individuals who have symptoms that suggest AATD or who have a family history of AATD should consider being tested [9]. Treatment Treatment of AATD depends on symptoms of a patient. There is currently no cure. The major goal of alpha 1 antitrypsin deficiency management is preventing or slowing the progression of lung disease. Treatments include bronchodilators and prompt treatment with antibiotics for upper respiratory tract infections. Lung transplantation may be an option for those who develop end-stage lung disease. Stopping smoking, if a patient with alpha 1 antitrypsin deficiency smokes, is essential. Replacement therapy with the missing alpha 1 antitrypsin protein is available, although it is used only under special circumstances. It is not known how effective this is once disease has developed or which people would benefit most.
population screening. Dis.140:961-6. Am. Rev. Respir.

References
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4. Janoff A, Carp H (1977) Possible mechanisms of emphysema in smokers: cigarette smoke condensate suppresses protease inhibition in vitro. Am. Rev. Respir. Dis. 116:65-72. 5. DeMeo DL, Silverman EK (2004) Alpha1antitrypsin deficiency, Genetic aspects of alpha (1)-antitrypsin deficiency: phenotypes and genetic modifiers of emphysema risk. Thorax 59:259-64.
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6. Parfrey H, Mahadeva R, Lomas DA (2003) Alpha (1)-antitrypsin deficiency, liver disease and emphysema. Int. J. Biochem. Cell Biol. 35:1009-14. 7. DeMeo DL, Campbell EJ, Brantly ML et al. (2009) Heritability of lung function in severe alpha-1 antitrypsin deficiency. Hum. Hered. 67:38-45.

8. Kumar V, Abbas AK, Fausto N, Robbin, Cotran (2005) Pathological basis of disease, 7th ed. Elsevier/Saunders. p. 911-2. 9. Kohnlein T, Welte T (1978) Alpha-1 antitrypsin deficiency: pathogenesis, clinical presentation, diagnosis, and treatment. Am. J. Med. 121:3-9.

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