Alpha-1-antitrypsin deficiency

Alpha-1-Antitrypsin Deficiency (AATD) is an inherited genetic condition that can affect the lungs, liver, skin, and blood vessels. Not everyone with AATD develops symptoms, and even people in the same family may be affected differently. What causes AATD? AATD is caused by changes (variants) in the SERPINA1 gene, which normally tells the liver to produce alpha-1-antitrypsin (AAT). AAT protects the lungs from damage caused by enzymes released during inflammation. In AATD: The liver doesn’t produce enough AAT, or Produces abnormally shaped AAT that gets trapped in the liver instead of entering the bloodstream. How AATD affects the body Lungs Low AAT levels allow lung tissue to be damaged, leading to: Emphysema Chronic bronchitis COPD Bronchiectasis Smoking is the biggest risk factor and can cause lung disease to appear 10–15 years earlier. Liver Misfolded AAT protein can build up in the liver, causing: Fibrosis Cirrhosis Liver failure Increased risk of liver cancer Children may show liver symptoms, including prolonged jaundice. Skin (rare) Painful nodules or ulcers (panniculitis) Blood vessels (very rare) Vasculitis causing fever, fatigue, aches, and weight loss Symptoms Symptoms usually begin after age 30, but can occur earlier. Common symptoms include: Shortness of breath, wheezing Chronic cough with mucus Fatigue and poor exercise tolerance Jaundice Unexplained weight loss Swelling of abdomen or legs Genetics and risk AATD is autosomal dominant You inherit one gene from each parent Two abnormal variants = higher disease risk One abnormal variant = carrier (usually no symptoms) Highest-risk genotype: PIZZ Lowest risk: PIMM AATD affects people worldwide but is underdiagnosed, especially outside Northern European populations. Complications Early-onset COPD Liver cirrhosis and liver cancer Skin and vascular inflammation Is there a cure? There is no cure, but early diagnosis allows: Smoking avoidance Lung-protective therapies Monitoring and treatment of liver disease Improved quality of life and normal lifespan in many non-smokers When to consider testing Family history of AATD, COPD, emphysema, or liver disease Lung disease at a young age Unexplained liver disease in adults or children Prevention & management Never smoke or quit immediately Avoid air pollutants and fumes Regular lung and liver monitoring Genetic counseling for family planning Early recognition makes a major difference in long-term outcomes.