Alpha-1 antitrypsin deficiency Flashcards
What is Alpha-1 antitrypsin deficiency and what organs are primarily affected?
Alpha-1 antitrypsin deficiency is a genetic condition characterized by low levels of alpha-1 antitrypsin, a protease inhibitor. It primarily affects the lungs and the liver.
Lung issues include chronic obstructive pulmonary disease (COPD) and bronchiectasis. Liver issues include dysfunction, fibrosis, cirrhosis, and potentially hepatocellular carcinoma.
What is the role of alpha-1 antitrypsin in the body, and what happens in its deficiency?
Alpha-1 antitrypsin inhibits neutrophil elastase, an enzyme that breaks down elastin in connective tissues. In deficiency, unopposed neutrophil elastase leads to lung tissue destruction, causing bronchiectasis and emphysema.
In the liver, a mutant version of the protein builds up in hepatocytes, causing inflammation, fibrosis, and cirrhosis.
How is alpha-1 antitrypsin deficiency inherited and what role does the genotype play?
Alpha-1 antitrypsin deficiency is inherited in an autosomal co-dominant pattern. The severity depends on the combination of both inherited copies of the SERPINA1 gene, located on chromosome 14.
This means both gene copies contribute to the disease outcome.
What are the clinical features of alpha-1 antitrypsin deficiency?
Lung-related: COPD, bronchiectasis, emphysema.
Liver-related: Liver dysfunction, fibrosis, cirrhosis, hepatocellular carcinoma.
Less common: Panniculitis, Granulomatosis with polyangiitis.
Lung issues typically appear after 30 years old, and smoking accelerates lung damage.
How is alpha-1 antitrypsin deficiency diagnosed?
Low serum alpha-1 antitrypsin levels, genetic testing for SERPINA1 gene mutations, lung damage assessment via imaging, and liver biopsy showing periodic acid-Schiff positive staining globules.
Imaging includes chest x-ray, high-resolution CT thorax, and pulmonary function tests.
What is the management for alpha-1 antitrypsin deficiency?
Stop smoking, symptomatic management for lung issues, organ transplant, screening of family members, and alpha-1 antitrypsin infusion.
Evidence for clinical benefit of infusion is limited and not recommended by NICE guidelines for COPD management.
