Alpha 1 Antitrypsin Deficiency

• Genetics: Chromosome 14 AR, more common in Europeans, Iberians, and Saudi Arabians (PiZ allele: 4% carrier, homozygotes 1:2000)

• Pathophysiology:

• Emphysema: AT inhibits neutrophil elastase, deficiency associated with increased elastase destruction of elastin with panacinar emphysema more prominent in lung bases: exacerbated by smoking RX elastase

• Hepatic Disease: only seen in 10-15% individuals homozygous for PiZ and Malton secondary to pathologic polymerization “loop-sheet” with accumulation of PAS positive, diastase negative granules in hepatocytes; increased risk in men Rx no effective therapy for liver disease other than transplantation

• HCC increased risk even in absence of cirrhosis

• Other complications:

• Necrotizing paniculitis

• MPGN Type I