Curriculum · Gastroenterology
Alpha-1-antitrypsin deficiency
What it is
Alpha1-antitrypsin deficiency is an inherited disorder in which defective alpha-1 antitrypsin accumulates. The protein is a protease inhibitor (Pi) coded on chromosome 14. Inheritance is given as autosomal recessive in one source and autosomal codominant in another, so both appear in the material. It attacks both the liver and the lung, and it is one of the listed causes of cirrhosis alongside alcohol, chronic hepatitis B or C, primary biliary cirrhosis, primary sclerosing cholangitis, drugs, toxins, hemochromatosis and Wilson disease.
How it presents
The liver side is associated with liver disease in infancy and childhood: prolonged neonatal jaundice, hepatomegaly, splenomegaly and bleeding from vit K deficiency. Around 10% to 20% of all infants with the genetic defect exhibit neonatal cholestasis, and 20% to 30% develop liver disease going on to cirrhosis and then failure. The lung side is emphysema in adults, with cough, wheezing and dyspnea. Put together, the disease leads to chronic hepatitis, cirrhosis and emphysema in early adulthood.