Alpha-1 antitrypsin deficiency: Year of the Zebra 2024

Alpha-1 antitrypsin, or AAT, deficiency is a genetic disorder in which a protein called alpha-1 antitrypsin is absent or defective.

The main function of AAT is to protect the lungs from damage caused by enzymes called proteases. These proteases can help fight off infections by breaking down proteins in bacteria, but they can also damage healthy tissues if their activity goes unchecked.

Without AAT, the lung’s proteases break down the elastic fibers in the air sac walls, resulting in destruction of healthy lung tissue.

The severity of the disorder varies depending on the amount of AAT in the blood. While some mutations result in little to no AAT being made, others, like the most common mutation, called Pi*Z, result in a misfolded AAT protein that gets trapped in the liver where they are normally produced, causing damage and ultimately death of liver cells.

People with Pi*Z mutations are at risk of both lung disease and liver damage, whereas those with non-Pi*Z mutations only have an increased risk of lung disease.

Symptoms of alpha-1 antitrypsin deficiency typically involve the lungs and liver. Damage to the lungs can result in shortness of breath, as well as wheezing, increased mucus production, and a chronic cough due to inflammation of the airways.

Ultimately, the death of liver cells can lead to cirrhosis, a process in which healthy liver tissue is replaced with scar tissue.

Long-term cirrhosis can lead to a number of complications, including easy bruising due to decreased production of clotting factors by the liver; jaundice, characterized by yellowing of the skin and eyes; and swelling in the abdomen and legs.

In some cases, chronic cirrhosis can predispose individuals to hepatocellular carcinoma, which is the most common primary liver cancer.

Aside from lung and liver manifestations, some individuals experience skin manifestations, including red nodules, bumps, or plaques in areas of the body with accumulation of subcutaneous fat like the buttocks, thighs, and abdomen.

Diagnosis of alpha-1 antitrypsin deficiency begins with a history and physical exam. The healthcare provider may order a chest X-ray or CT scan to look for evidence of damaged lung tissue; as well as pulmonary function tests, like spirometry, to see how well the lungs are functioning.

Additionally, an abdominal ultrasound may be performed to look for signs of cirrhosis, such as a lumpy or irregular liver.

In suspected cases, diagnosis can be confirmed by measuring AAT levels in the blood. Then, genetic testing can be done to detect the exact mutation causing the disease.

For treatment, individuals may be given replacement therapy with AAT derived from plasma donors. This can help raise blood levels of AAT, but it doesn’t cure the disorder, so other therapies like bronchodilators and supplemental oxygen are often needed.

Since replacement therapy doesn’t resolve liver problems, standard treatment for cirrhosis is also necessary. Finally, smoking cessation is essential for individuals with alpha-1 antitrypsin deficiency, as smoking can accelerate lung damage and lead to an earlier onset of lung disease.

Alright, as a quick recap, alpha-1 antitrypsin deficiency is a genetic disorder that mainly causes damage to the lungs, leading to symptoms like shortness of breath, wheezing, and coughing.

In some cases, defective alpha-1 antitrypsin can accumulate in the liver, leading to cirrhosis. Diagnosis is made using blood and genetic testing.

Treatment focuses on supportive measures to improve respiratory symptoms and replacement therapy with alpha-1 antitrypsin to slow the progression