Alpha 1 Antitrypsin Deficiency

Causes

Alpha-1 antitrypsin deficiency is congenital lack of a primary lung antiprotease, alpha-1 antitrypsin, which leads to increased protease-mediated tissue destruction and emphysema in adults. Hepatic accumulation of abnormal alpha-1 antitrypsin can cause liver disease in both children and adults.

Symptoms and Signs

Neonates with hepatic involvement present with cholestatic jaundice and hepatomegaly during the first week of life; jaundice usually resolves by 2 to 4 mo of age. Cirrhosis may develop in childhood or adulthood. Adults with emphysema have symptoms and signs of COPD, including dyspnea, cough, wheezing, and prolonged expiration.

Diagnosis

• Serum alpha-1 antitrypsin level
• Genotyping

Prognosis

As a group, people with severe alpha-1 antitrypsin deficiency who have never smoked have a normal life expectancy and only moderate impairment of pulmonary function. The most common cause of death in alpha-1 antitrypsin deficiency is emphysema, followed by cirrhosis, often with hepatocellular carcinoma.

Treatment

• Supportive care
• For pulmonary disease, often alpha-1 antitrypsin replacement
• Gene therapy is under study