Alpha-1 antitrypsin deficiency
α1-AT PiM (protease inhibitor M) protein is secreted by the liver into the circulation
it is also produced by lung epithelial cells and monocytes
α1-AT and other serum antiproteases help inactivate proteolytic enzymes released from dead bacteria or leukocytes in the lung.
M is the normal allele, Z is main deficiency allele, homozygosity producing protein Z
Mutant protein is not produced (null), or is misfolded (PiZ and others); it can polymerize in the endoplasmic reticulum or be degraded, with subsequent low serum levels.
PiZZ homozygotes represent the majority of lung and liver disease, misfolded protein is not secreted from hepatocytes
Pi-- (null) = no protein = severe lung disease, but no liver disease because no accumulation of protein
neonatal cholestasis/non-infectious hepatitis/cirrhosis
angiooedema
Emphysema: early-onset severe panacinar pulmonary emphysema at 20-40yo
Panniculitis (with Z-type)
- subcutaneous tender red nodules
- ulcerate and self discharge yellow oily fluid