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alpha-1-antitrypsin Deficiency, (α1-antitrypsin or AAT Deficiency)

March 31, 2025Chemical pathologyLab Tests

Table of Contents

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  • alpha-1-antitrypsin Deficiency
        • What sample is needed for alpha-1-antitrypsin Deficiency?
        • What are the Indications for alpha-1-antitrypsin Deficiency?
        • What are the precautions for alpha-1-antitrypsin Deficiency?
        • How will you define alpha-1-antitrypsin deficiency?
        • How will you discuss the pathophysiology of alpha-1-antitrypsin Deficiency?
        • What is the etiology of α1-Antitrypsin Deficiency?
        • What is the clinical presentation of the Alpha-1-antitrypsin deficiency?
        • What is the presentation of the Alpha 1-Antitrypsin Deficiency?
        • How will you diagnose Alpha-1-antitrypsin deficiency?
        • What are the normal alpha-1-antitrypsin levels?
          • Source 2
        • What are the causes of raised alpha-1-antitrypsin Deficiency (AAT)?
        • What are the causes of decreased alpha-1-antitrypsin Deficiency (AAT)?
      • Questions and answers:

alpha-1-antitrypsin Deficiency

What sample is needed for alpha-1-antitrypsin Deficiency?

  1. The patient needs to fast for several hours before giving the sample.
  2. This test is done in the serum or plasma.
    1. Separate the serum immediately and store it properly.
  3. Take 3 to 5 ml of blood in the disposable syringe.
    1. Keep the syringe for 15 to 30 minutes, then centrifuge for 2 to 4 minutes. This will yield a clear serum.
  4. Serum or plasma is stable for ≥ 7 days at 4 °C.
    • At -70 °C, it is stable for 3 months.

What are the Indications for alpha-1-antitrypsin Deficiency?

  1. This helps in the diagnosis of juvenile and adult cirrhosis of the liver.
  2. For neonatal respiratory distress syndrome.
  3. For emphysema (there is a deficiency or absence of this enzyme).
  4. This is useful for the diagnosis of familial chronic obstructive lung disease.
  5. This enzyme may be deficient in a protein-losing disorder.
  6. This is also an acute-phase protein raised in inflammation, infections, and malignancy.

What are the precautions for alpha-1-antitrypsin Deficiency?

  1. This is raised during pregnancy.
  2. Oral contraceptives increase the level of AAT.
  3. Any inflammatory process will raise the AAT level because it is raised by inflammation.

How will you define alpha-1-antitrypsin deficiency?

  1. Alpha-1-anti-trypsin deficiency is a genetic disorder that affects the production of a protein called alpha-1-anti-trypsin.
  2. It protects the lungs from the damage caused by an enzyme released during inflammation.

How will you discuss the pathophysiology of alpha-1-antitrypsin Deficiency?

  1. This is present in the alpha-globulin fraction, mainly consisting of the glycoprotein.
    1. AAT deficiency is autosomal recessive, present on chromosome 14.
    2. This is a serine protease inhibitor; the main substrate is neutrophil elastase, which, when unchecked, is associated with familial pulmonary emphysema and liver diseases.
    3. The heterozygous state occurs in 10% to 15% of the general population, with a serum level of AAT ∼60% of the normal.
      1. Homozygous patients are seen in 1:2000 persons with a serum level ∼of 10% of the normal.
    4. AAT is a relatively small size and can diffuse into the tissues. It is important in preventing loss of elastic recoil.
    5. The deficiency of AAT or excess of elastase in uninhibited elastase in the bronchial tree leads to emphysema.
Alpha-1-antitrypsin deficiency (AAT) electrophoresis

Alpha-1-antitrypsin deficiency (AAT) electrophoresis

  1. This is the most potent protein (AAT), which inhibits proteolytic enzymes produced by neutrophils during inflammation and the phagocytic process.
alpha-1-antitrypsin (AAT) proteolytic enzyme activity

Alpha-1-anti-trypsin (AAT) proteolytic enzyme activity

  1. This is also called an α-1 proteinase inhibitor.
    1. AAT is the highest concentration proteinase inhibitor in the plasma on a molar basis.
    2. This is the most important inhibitor of the leucocyte elastase, which is produced in inflammation for phagocytosis.
    3. This enzyme reacts with elastin in the tracheobronchial system and the vascular endothelium.
  2. This is synthesized in the liver by hepatocytes.
  3. Catabolism is also taken by the liver parenchymal cells. This takes two routes:
    1. The serpin-enzyme complex receptor removes the AAT-protease complex.
    2. The asialoglycoprotein receptors remove desialylated AAT.
  4. It breaks enzymes like Trypsin, Chymotrypsin, Elastase, Thrombin, and Plasmin.
Alpha-1- antitrypsin metabolism

Alpha-1- antitrypsin metabolism

  1. Its level rises non-specifically in acute inflammations, severe infections, and necrosis.
Alpha-1-antitrypsin (AAT) functions and inhibition

Alpha-1-antitrypsin (AAT) functions and inhibition

What is the etiology of α1-Antitrypsin Deficiency?

  1. Genetic.
  2. Acquired.
  3. There are 75 known variants of the AAT, some of which are associated with a low concentration of AAT.
  4. Pi MM’s most common phenotypes and the most common deficiency of phenotypes are Pi ZZ and Pi SZ.
  5. Its deficiency gives rise to lung and liver diseases.
  6. This enzyme protects the lungs from the elastase enzyme action.
Alpha-1-antitrypsin (AAT) role in lung emphysema

Alpha-1-antitrypsin (AAT) role in lung emphysema

  1. Acquired deficiency may be seen in protein deficiency, such as malnutrition, liver diseases, Nephrotic syndrome, and neonatal respiratory distress syndrome.

What is the clinical presentation of the Alpha-1-antitrypsin deficiency?

  1. People with a1a (AAT) deficiency develop emphysema in the 3rd or 4th decades of life.
  2. Congenital deficiency of ATT results in premature emphysema.
  3. An inherited AAT deficiency is associated with symptoms in early life, unlike the acquired AAT deficiency.
    1. Inherited AAT deficiency is associated with liver and biliary diseases.
    2. Homozygous people have severe pulmonary and liver disease very early in life.
    3. 5% to 14% of the adult population is in the heterozygous state and is considered at greater risk for developing emphysema.
  4. Chronic bronchitis is prominent with a1a (AAT) deficiency who smoke.
    1. Cigarette smoking and other volatile irritants stimulate the release of enzymes from the white blood cells in the lung.
    2. Without the presence of ATT, these enzymes destroy the lung parenchyma.
    3. There will be Severe emphysema, usually seen in the 3rd or 4th decades.
alpha-1-antitrypsin (AAT) and cigarette smoking leading to emphysema

alpha-1-antitrypsin (AAT) and cigarette smoking leading to emphysema

  1. This is a positive acute-phase protein.
  2. This enzyme deficiency is an inherited disorder that gives rise to liver and lung diseases.
    1. There are 75 known genetic variants of AAT associated with deficiency.
    2. The most common phenotype is Pi MM, and the deficiency of AAT is Pi ZZ and SZ.
  3. The congenital decrease may cause the early onset of:
    1. Emphysema.
    2. Infantile hepatitis ultimately leads to cirrhosis.
    3. Neonatal cholestasis or hepatitis is present most commonly at 3 to 8 weeks of age.
    4. Extrahepatic and intrahepatic bile ducts may be small because of decreased bile flow.
    5. Hepatocellular carcinoma.
  4. This is inherited as an autosomal codominant trait.
  5.  There is a mutation in the gene SERPINA1.
  6. There are two common diseases, emphysema and liver cirrhosis.
  7. This is also seen in liver diseases like:
    1. Neonatal cholestasis or hepatitis is common at the age of 3 to 8 weeks and regresses after a few weeks.
      1. Differentiation from the biliary atresia is significant.
      2. Because there is very high mortality if surgery is done in patients with Pi ZZ infants.
    2. Cirrhosis.
    3. Hepatocellular carcinoma.

What is the presentation of the Alpha 1-Antitrypsin Deficiency?

  1. There is tiredness.
  2. Patients have shortness of breath and wheezing.
  3. Pulmonary emphysema is seen in heterozygotes and homozygotes.
  4. Secondary bronchitis and bronchiectasis may be seen in these patients.
Alpha-1-antitrypsin deficiency presentation

Alpha-1-antitrypsin deficiency presentation

How will you diagnose Alpha-1-antitrypsin deficiency?

  1. This disease can be diagnosed:
    1. Estimation of a1-antitrypsin in the blood.
    2. Genetic analysis (Genotype or phenotype of the blood).
    3. A sample of DNA from the mouth cell to detect α1-antitrypsin.
    4. Routine serum protein electrophoresis is a good screening test for AAT deficiency.
      • 90% of the AAT is in the α1-globulin portion.

What are the normal alpha-1-antitrypsin levels?

  • Newborn
  • 145 to 270 mg/dL
  • Adult
  • 78 to 200 mg/dL
  • >60 years
  • 115 to 200 mg/dL
Source 2
  • Normal = 85 to 213 mg/dL (0.85 to 2.13 g/L).

Source 4

  • 100 to 200 mg/dL (18.4 to 36.8 µmol/L) by nephelometry.
  • The critical value for deficiency = is around 35 mg/dL
  • The patient with serum AAT <70 mg/dL (<12.9 µmol/L) may have a homozygous deficiency and risk developing early lung disease.

What are the causes of raised alpha-1-antitrypsin Deficiency (AAT)?

  1. Inflammatory disorders.
  2. Cancers, especially cervical carcinoma and lymphomas.
  3. Hormonal effects.
  4. Systemic lupus erythematosus.
  5. Brain infarction.
  6. Hashimoto’s thyroiditis.
  7. Pregnancy.
  8. Oral contraceptive tablets.

What are the causes of decreased alpha-1-antitrypsin Deficiency (AAT)?

  1. Typically <50 mg/dL.
  2. Kidney diseases like Nephrotic syndrome.
  3. Prematurity.
  4. Malnutrition.
  5. Liver diseases like acute hepatitis.
  6. In the lungs as respiratory distress syndrome and Emphysema.
  7. Protein-losing gastroenteropathies.
  8. Pancreatitis.
  9. Congenital defects.
  10. AAT levels are  secondarily low in patients like:
    1. Neonatal respiratory distress syndrome.
    2. Severe pancreatitis.
    3. Protein-losing disorders.

Questions and answers:

Question 1: What is the role of cigarette smoking in alpha-1-deficiency?
Show answer
Cigarette smoking leads to the release of the proteolytic enzymes from the WBCs, which will cause damage to the lungs.
Question 2: AAT deficiency on which chromosome is present?
Show answer
AAT deficiency gene is present on chromosome 14.

Possible References Used
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