Alpha 1 Anti Trypsin: Pi*MM, Pi*MZ, Pi*ZZ, Pi*null
Alpha1 antitrypsin (α1 AT) deficiency is the only known genetic abnormality that leads to COPD; it accounts for less than 1% of COPD in the United States.
Basilar-predominant hyperlucency on chest imaging -> early-onset emphysema (eg, before age 55).
Occurrence of emphysema in a non- or trivial-smoker, or a family history of liver or lung disease.
WHY? Unimpeded neutrophil elastase contributes to the alveolar destruction of emphysema.
NAMING (disease is inherited co-dominant)
Pi*S (essentially normal; leading to a mild decrease in circulating A1-PI)
Pi*null– They do NOT make any alpha-1 antitrypsin. The rare null variants that are characterized by complete absence of AAT synthesis; does not cause liver disease.
Pi*MZ– heterozygous. Heterozygotes are not deemed to be at significant risk of developing emphysema.
PI*ZZ– Homozygotes for the severe deficiency allele Z. Most* but not all severely deficient individuals develop emphysema, risk for which is markedly increased by smoking. For liver disease, the lifetime risk is estimated to be approximately 40%.
*More than 95% of persons in the severely deficient category are homozygous for the Z allele, designated PiZZ.
Craig TJ. Suspecting and Testing for Alpha-1 Antitrypsin Deficiency-An Allergist’s and/or Immunologist’s Perspective. J Allergy Clin Immunol Pract. 2015 Jul-Aug;3(4):506-11. doi: 10.1016/j.jaip.2015.04.005. Epub 2015 May 29.
Stoller JK, Aboussouan LS. A review of α1-antitrypsin deficiency. Am J Respir Crit Care Med. 2012;185:246–59.
de Serres F, Blanco I. Role of alpha-1 antitrypsin in human health and disease. J Intern Med. 2014;276:311–35.