Alpha-1-antitrypsin deficiency (AATD)

Alpha-1-antitrypsin deficiency (AATD) is a genetic disorder characterized by reduced levels of alpha-1-antitrypsin (AAT) in the blood, which leads to an increased risk of lung and liver diseases. The condition is caused by mutations in the SERPINA1 gene, which encodes for AAT protein.

Case:
John is a 35-year-old male who presents with shortness of breath and wheezing. He has a history of smoking and a family history of lung disease. A chest X-ray reveals emphysematous changes. John’s physician suspects AATD and orders further testing.

Pathophysiology:

AAT is a protease inhibitor that helps protect lung tissue from damage caused by enzymes released by immune cells. In AATD, the decreased levels of AAT in the blood result in the uncontrolled destruction of lung tissue, leading to emphysema and chronic obstructive pulmonary disease (COPD). The liver is also affected in some cases, with the accumulation of misfolded AAT protein causing liver disease.

Signs and Symptoms:

The signs and symptoms of AATD are similar to those of COPD, including shortness of breath, wheezing, cough, and chest tightness. Symptoms may develop at a younger age and progress more rapidly than in people without AATD. Liver disease symptoms can include jaundice, abdominal pain, and swelling.

Investigation:

AATD can be diagnosed with a blood test to measure AAT levels and genetic testing to identify the mutations in the SERPINA1 gene. Lung function tests, chest X-rays, and CT scans may also be used to assess the severity of lung disease.

Treatment:

Treatment for AATD includes managing the symptoms of lung and liver disease. Smoking cessation is crucial in preventing further lung damage. Bronchodilators and steroids can be used to alleviate symptoms. In severe cases, oxygen therapy and lung transplantation may be necessary. Treatment for liver disease may include medication and, in rare cases, liver transplantation.

Advise (Dos and Don’ts):

People with AATD should avoid smoking and exposure to environmental toxins that can worsen lung disease. It is also essential to maintain a healthy lifestyle, including regular exercise and a balanced diet. Regular medical checkups are necessary to monitor lung and liver function.

Reference:

• American Lung Association
• National Heart, Lung, and Blood Institute
• Alpha-1 Foundation
• Stoller, J. K., Aboussouan, L. S., & Kanner, R. E. (2019). Alpha-1 antitrypsin deficiency: A review of current diagnostic and treatment options. Respiratory medicine, 147, 41-50.
• Soriano, J. B., Vestbo, J., & Pride, N. B. (2017). Evaluation of the efficacy and safety of alpha-1-antitrypsin augmentation therapy in the treatment of patients with emphysema. Expert opinion on biological therapy, 17(11), 1371-1380.
• Stoller, J. K., & Sandhaus, R. A. (2012). Alpha-1 antitrypsin deficiency: diagnosis, pathophysiology, and management. The Journal of the American Medical Association, 308(14), 1468-1479.