Alpha 1-antitrypsin deficiency (AATD) is a genetic disorder that affects the production of a protein called alpha 1-antitrypsin (AAT) in the liver. This condition was first identified in the early 1960s by Dr. Carl-Bertil Laurell and Dr. Sten Eriksson, who noticed a deficiency of AAT in the blood of patients with emphysema.
AAT is an important protein that helps protect the lungs from damage caused by enzymes released by white blood cells. These enzymes, called proteases, can break down lung tissue if not properly regulated. AAT acts as an inhibitor of these proteases, preventing them from causing harm. However, individuals with AATD have low levels of AAT or produce a dysfunctional form of the protein, leaving their lungs vulnerable to damage.
The discovery of AATD led to further research into its genetic basis. It was found that AATD is caused by mutations in the SERPINA1 gene, which provides instructions for making AAT. The most common mutation associated with AATD is called the Z mutation, named after the abnormal protein it produces. This mutation leads to the accumulation of abnormal AAT in the liver, preventing it from being released into the bloodstream.
Over time, researchers have identified different variants of AATD, each associated with varying degrees of AAT deficiency and disease severity. The S and Z variants are the most common, with the Z variant being the most severe. Individuals who inherit two copies of the Z variant (ZZ genotype) are at the highest risk of developing lung and liver diseases.
The clinical manifestations of AATD primarily affect the lungs and liver. In the lungs, AATD can lead to the development of emphysema, a condition characterized by the destruction of lung tissue and difficulty breathing. In the liver, the accumulation of abnormal AAT can cause liver disease, such as cirrhosis and hepatitis.
Since its discovery, significant progress has been made in understanding AATD and its impact on health. Diagnostic tests have been developed to measure AAT levels in the blood and identify individuals with AATD. Genetic counseling and testing are available to help individuals understand their risk of passing on the condition to their children.
Treatment options for AATD include augmentation therapy, which involves regular infusions of purified AAT to increase its levels in the blood. This therapy can help slow down the progression of lung disease in individuals with severe AATD. Other treatments focus on managing symptoms and preventing complications.
Research efforts continue to explore new therapies and interventions for AATD. The development of gene therapies and targeted drugs holds promise for future treatments that may address the underlying genetic cause of AATD.