Alpha-1 Antitrypsin Deficiency
Also known as: AATD, Alpha1-antitrypsin deficiency, Alpha-1 protease inhibitor deficiency
Alpha-1 Antitrypsin Deficiency (AATD) is a genetic disorder characterized by a deficiency of alpha-1 antitrypsin (AAT), a protein primarily produced in the liver that protects the lungs from damage caused by enzymes like elastase. The deficiency can lead to lung diseases, such as emphysema and chronic obstructive pulmonary disease (COPD), as well as liver disease, including cirrhosis and hepatocellular carcinoma. The severity and onset of symptoms vary widely among affected individuals.
Imagine your lungs have tiny protectors called Alpha-1. If you don't have enough of them because of a problem you got from your parents, your lungs can get damaged, making it hard to breathe. Sometimes, it can also hurt your liver. Doctors can give you medicine to help protect your lungs, and it's super important not to smoke!
Signs & Symptoms
- Shortness of breath
- Wheezing
- Chronic cough
- Sputum production
- Fatigue
- Unintentional weight loss
- Vision problems
- Liver problems (jaundice, abdominal swelling)
- Skin problems (panniculitis)
Treatment Options
Augmentation Therapy (AAT protein infusions)
MODERATELY EFFECTIVE Approved 1987Bronchodilators
SUPPORTIVEInhaled Corticosteroids
SUPPORTIVEAntibiotics (for respiratory infections)
SUPPORTIVEPulmonary Rehabilitation
SUPPORTIVEOxygen Therapy
SUPPORTIVELung Transplantation
HIGHLY EFFECTIVELiver Transplantation
HIGHLY EFFECTIVEGene Therapy
EXPERIMENTALDiagnosis
- Alpha-1 antitrypsin (AAT) blood test
- Genetic testing (to identify specific mutations in the SERPINA1 gene)
- Pulmonary function tests (spirometry)
- Liver function tests
- Liver biopsy (in some cases)
- Chest X-ray or CT scan
History
AATD was first described by Carl-Bertil Laurell and Sten Eriksson in Sweden in 1963, who noted the association between AAT deficiency and early-onset emphysema. The genetic basis of the disease was later elucidated, leading to the development of diagnostic tests and augmentation therapy.
Recent Breakthroughs
Novel Gene Therapy Approaches for AATD
Research is ongoing to develop gene therapy strategies that can correct the SERPINA1 gene defect and restore normal AAT production in the liver. Several clinical trials are evaluating the safety and efficacy of adeno-associated virus (AAV) vectors to deliver a functional SERPINA1 gene to hepatocytes.
Small Molecule Correctors for AAT Protein Misfolding
Researchers are investigating small molecule compounds that can stabilize the AAT protein and prevent its misfolding and accumulation in the liver, potentially reducing liver damage and increasing circulating AAT levels.