Alpha-1 antitrypsin deficiency

- autosomal recessive
- defective gene in chromosome 14
- alpha-1 antitrypsin protein is synthesized by hepatic cells and released into circulation. In lungs, its primary function is to inactivate neutrophil elastase (enzyme released during phagocytosis in alveolus)
- encoded by protease inhibitor (Pi) locus
- most common (90%) allele is M (PiM). Normal is homozygous (PiMM)
- PiZZ have only 15-20% of normal blood alpha-1 antitrypsin level, which is severe
- Heterozygotes (PiMZ, PiMS, PiSZ) have less severe phenotypes
- smoking is the greatest risk factor for development of emphysema in adults with alpha-1 antitrypsin deficiency
- lung compliance increased in emphysema
- majority of patients with clinical liver disease are homozygotes with PiZZ phenotype, which can produce jaundice and liver problems in neonates within few days of birth