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Alpha-1-Antitrypsin

25 Azn
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Alpha-1-antitrypsin (AAT) is a protein produced by the liver. In addition to aiding the body in enzyme breakdown, its primary function is to protect the lungs from elastase, an enzyme released by neutrophils in response to injury and inflammation. Elastase breaks down proteins, which are then processed and eliminated by the body. If its activity is not regulated by alpha-1-antitrypsin, it starts damaging lung tissue.

Liver Accumulation and Genetic Deficiency:
Dysfunctional alpha-1-antitrypsin accumulates in the liver cells that produce it. The accumulated defective AAT forms abnormal protein chains that begin to destroy cells and damage the liver. Around 10% of patients with AAT deficiency experience jaundice in infancy. Most recover, but in severe cases, affected children require a liver transplant to survive. Currently, AAT deficiency is the most common liver disease in pediatrics.

Genetic Influence on Alpha-1-Antitrypsin Levels:
The quantity and activity of alpha-1-antitrypsin depend on the type of inherited mutation. Although the SERPINA1 gene has over 75 known alleles, only a few are widespread.

  • Phenotyping of AAT-producing genes helps identify the forms of the protein and compare them with known isoforms.
  • DNA sequencing of genes involved in AAT production helps detect mutations in the SERPINA1 gene (protease inhibitor gene). Typically, only the most common mutations (M, S, Z) are identified.
  • Genetic testing can be used for screening patients and family members at risk of AAT deficiency.

Biomaterial: Venous blood.
Pre-test recommendations:

  • Do not eat for 12 hours before the test.
  • Stop taking medications 24 hours before the test (with your doctor’s approval).
  • Avoid alcohol for 24 hours before the test.
  • Do not smoke for 3 hours before the test.
  • If jaundice lasts more than 1–2 weeks in a newborn or young child, or if there are signs of liver damage (e.g., enlarged spleen, blisters, itching).
  • If a patient under 40 years old has chronic wheezing, bronchitis, sudden shortness of breath after exercise, or other emphysema symptoms, especially if they don’t smoke or aren’t exposed to lung irritants but have lung disease.
  • If a close relative has AAT deficiency.

Clinical Significance

  • Lower AAT levels indicate a higher risk of emphysema.
  • The consequences of defective AAT production depend on the amount and type of abnormal genes. This may lead to lung disease (due to lack of protection) or liver disease (due to protein accumulation).
  • Reduced AAT production is associated with one or two abnormal copies of the SERPINA1 gene. However, the severity of deficiency and its impact on lung/liver health can vary widely between individuals with the same mutation.

Other Conditions Affecting AAT Levels

  • Acute & chronic inflammatory diseases, infections, and some cancers can cause fluctuations in AAT levels.
  • Newborns with respiratory diseases may have temporarily low AAT levels.
  • Low total protein due to kidney disease (nephrotic syndrome), malnutrition, or certain cancers can also reduce AAT concentration.