Aat Deficiency

• AAT Deficiency is a genetic condition causing low levels of alpha-1 antitrypsin, a protein vital for protecting the lungs.
• It primarily affects the lungs, leading to conditions like emphysema, and can also cause liver damage.
• The condition is inherited, meaning it is passed down through families via specific gene mutations.
• Common symptoms include shortness of breath, wheezing, and recurrent respiratory infections.
• Treatment often involves augmentation therapy, which replenishes the deficient protein, alongside supportive care.

What is Alpha-1 Antitrypsin (AAT) Deficiency?

Alpha-1 antitrypsin deficiency (AAT deficiency) is an inherited genetic disorder characterized by low levels of alpha-1 antitrypsin (AAT), a protein made in the liver. This protein plays a crucial role in protecting the lungs from inflammation and damage caused by enzymes, particularly neutrophil elastase. When AAT levels are insufficient, these enzymes can freely attack lung tissue, leading to progressive damage, most notably emphysema.

The condition is one of the most common genetic causes of chronic obstructive pulmonary disease (COPD) in adults and can also lead to liver disease in both children and adults. According to the Alpha-1 Foundation, AAT deficiency affects approximately 1 in 3,000 to 5,000 people of European descent, though it can occur in all ethnic groups. Understanding what is AAT deficiency is crucial for early diagnosis and management, as many individuals remain undiagnosed for years, often misdiagnosed with more common forms of COPD or asthma.

Symptoms and Causes of AAT Deficiency

The primary causes of AAT deficiency are genetic mutations in the SERPINA1 gene, which provides instructions for making the alpha-1 antitrypsin protein. The most common severe deficiency alleles are PiZ and PiS. Individuals who inherit two copies of the PiZ allele (ZZ genotype) typically have the lowest AAT levels and are at the highest risk for severe lung and liver disease. The abnormal AAT protein produced by these mutations cannot be released from the liver effectively, leading to its accumulation in liver cells, which can cause liver damage, while simultaneously resulting in a deficiency of AAT in the bloodstream and lungs.

The AAT deficiency symptoms can vary widely among individuals, depending on the severity of the deficiency and whether the lungs or liver are primarily affected. Lung symptoms often manifest in adulthood, typically between the ages of 20 and 50, and can include:

• Shortness of breath, especially with exercise
• Wheezing
• Chronic cough and sputum production
• Recurrent respiratory infections, such as bronchitis or pneumonia
• Fatigue
• Unintended weight loss

Liver symptoms, which can appear at any age, from infancy to adulthood, may include jaundice (yellowing of the skin and eyes), swelling of the abdomen and legs, and impaired liver function. Some individuals may develop cirrhosis or liver cancer. It is important to note that some people with AAT deficiency may experience mild or no symptoms, especially if their AAT levels are only moderately reduced.

Treatment for AAT Deficiency

The primary AAT deficiency treatment for lung disease is augmentation therapy. This involves intravenous infusions of purified human alpha-1 antitrypsin protein, which helps to raise the levels of AAT in the blood and lungs, thereby protecting the lung tissue from further damage. Augmentation therapy is generally recommended for individuals with confirmed AAT deficiency and established emphysema, or those with significant airflow obstruction. It is not a cure but aims to slow the progression of lung disease.

In addition to augmentation therapy, supportive treatments are crucial for managing AAT deficiency. These include bronchodilators and corticosteroids to manage lung symptoms, antibiotics for respiratory infections, and pulmonary rehabilitation to improve lung function and quality of life. For individuals with severe lung damage, lung transplantation may be an option. For those with liver disease, treatment focuses on managing symptoms and complications, which may include medications to reduce fluid retention or, in severe cases, liver transplantation. Lifestyle modifications, such as avoiding smoking and exposure to lung irritants, are also vital for all individuals with AAT deficiency to minimize further lung damage.