Alpha-1 antitrypsin (AAT)

Alpha-1 antitrypsin (AAT) deficiency is a genetic disorder characterized by low levels of a protein called alpha-1 antitrypsin (AAT) in the blood. AAT is produced by the liver and serves a crucial role in protecting tissues from damage caused by enzymes released by white blood cells, especially in the lungs and liver.

Here’s a breakdown of what happens with this condition:

• Genetics: AAT deficiency is inherited in an autosomal co-dominant manner, meaning that both copies of the gene (one from each parent) can contribute to the condition. The most common genetic variants associated with AAT deficiency are the M (normal), S (deficient), and Z (severely deficient) alleles. Individuals with the ZZ genotype have the most severe form of the deficiency.
• Lung Issues: Low levels of AAT can lead to increased damage to lung tissue due to unchecked activity of enzymes like neutrophil elastase. This can result in chronic lung diseases such as emphysema and chronic obstructive pulmonary disease (COPD).
• Liver Issues: The liver is responsible for producing AAT, and in AAT deficiency, abnormal AAT proteins accumulate in liver cells, leading to liver damage. This can manifest as liver inflammation, cirrhosis, or liver failure.
• Symptoms: Symptoms can vary widely. In the lungs, they may include shortness of breath, wheezing, and chronic cough. Liver symptoms may include jaundice (yellowing of the skin and eyes), abdominal pain, and swelling.
• Diagnosis: AAT deficiency is diagnosed through blood tests that measure AAT levels and genetic tests that identify the specific genetic variants. Liver biopsy or imaging might be used to assess liver damage.
• Treatment: While there’s no cure, treatments can manage symptoms and prevent complications. For lung issues, treatments may include bronchodilators, steroids, and lifestyle changes like quitting smoking. For liver issues, management might involve addressing complications and sometimes liver transplantation in severe cases. AAT replacement therapy, where purified AAT protein is administered, can be used for some individuals with significant lung problems.

Early diagnosis and management are crucial to improving outcomes and quality of life for individuals with AAT deficiency.