[1][2] Complications may include chronic obstructive pulmonary disease (COPD), cirrhosis, neonatal jaundice, or panniculitis.

[1] Risk factors for lung disease include tobacco smoking and environmental dust.

[2] Treatment of lung disease may include bronchodilators, inhaled steroids, and, when infections occur, antibiotics.

[9] Apart from COPD and chronic liver disease, α1-antitrypsin deficiency has been associated with necrotizing panniculitis (a skin condition) and with granulomatosis with polyangiitis in which inflammation of the blood vessels may affect a number of organs but predominantly the lungs and the kidneys.

[11] The most common cause of severe deficiency, PiZ, is a single base-pair substitution leading to a glutamic acid to lysine mutation at position 342 (dbSNP: rs28929474), while PiS is caused by a glutamic acid to valine mutation at position 264 (dbSNP: rs17580).

[14] With A1AT deficiency, neutrophil elastase can disrupt elastin and components of the alveolar wall of the lung that may lead to emphysema, and hypersecretion of mucus that can develop into chronic bronchitis.

However, in individuals with the PiZZ genotype, A1AT levels are less than 15% of normal, and they are likely to develop panlobular emphysema at a young age.

[7] In addition to increasing the inflammatory reaction in the airways, cigarette smoke directly inactivates alpha-1 antitrypsin by oxidizing essential methionine residues to sulfoxide forms, decreasing the enzyme activity by a factor of 2,000.

[citation needed] The accumulation of these inclusions or globules is the main cause of liver injury in A1AT deficiency.

[9] The gold standard of diagnosis for A1AD consists of blood tests to determine the phenotype of the AAT protein or genotype analysis of DNA.

[9] Liver biopsy is the gold standard for determining the extent of hepatic fibrosis and assessing for the presence of cirrhosis.

A low level of A1AT confirms the diagnosis and further assessment with A1AT protein phenotyping and A1AT genotyping should be carried out subsequently.

Other variants are less functional and are termed A-L and N-Z, dependent on whether they run proximal or distal to the M band.

Some mutant forms fail to fold properly and are, thus, targeted for destruction in the proteasome, whereas others have a tendency to polymerize, thereafter being retained in the endoplasmic reticulum.

The serum levels of some of the common genotypes are:[citation needed] Treatment of lung disease may include bronchodilators, inhaled steroids, and, when infections occur, antibiotics.

[2] People with lung disease due to A1AD may receive intravenous infusions of alpha-1 antitrypsin, derived from donated human plasma.

[11] As of 2015 there were four IV augmentation therapy manufacturers in the United States, Canada, and several European countries.

Individuals with cirrhosis and portal hypertension should avoid contact sports to minimize the risk of splenic injury.

[21] The highest prevalence of the PiZZ variant was recorded in the northern and western European countries with mean gene frequency of 0.0140.

[23] Laurell, along with a medical resident, Sten Eriksson, made the discovery after noting the absence of the α1 band on protein electrophoresis in five of 1500 samples; three of the five patients were found to have developed emphysema at a young age.