Contributed by Dr. Diane Cox, PhD, FCCMG
Alpha1-antitrypsin (AAT) is the major protease inhibitor in serum. Preliminary testing for abnormalities of AAT is by quantitation of the protein in serum. However if the value is low, further follow up is required to determine which genetic type of AAT (Pi type) is present. This information is of importance in some cases for prognosis and may be important for other members of the family in altering their environment and lifestyle to avoid developing disease. Pi typing would be indicated when the concentration of AAT is:
Less than 200 mg% alpha1-AAT (about 75% of normal) (A higher cut off point might be used, e.g. 230 mg%, for women on oral contraceptives)
Quantitation of AAT is not reliable in identifying the genetic type of an individual. Even those who are deficient (Pi type ZZ) can have elevations of alpha1-AAT to about 50% of normal levels during childhood or during an inflammatory process. There is considerable overlap between individuals of Pi type SZ (who have levels somewhat higher than ZZ generally) and MZ individuals. For this reason, quantitation can act only as a guide to further study of those who show low values. Relatives of patients with low AAT should be tested by Pi Typing, not quantitative assay.
More than 20 different genetic types have been described, however, there is only one common deficiency type, Z. The following in a brief description of the Pi types most commonly found in the population.
MM: about 90% of the normal population. These individuals have what we would call the ‘normal’ amount of AAT.
MS: about 8% of the normal population. These individuals carry the normal M type of AAT plus a relatively common S type. These individuals are not known to be more prone to lung disease than anyone else in the population.
MZ: about 3% of the normal population. These individuals have normal M AAT plus an abnormal Z type, which is associated with low levels of AAT. Such individuals generally have less than 75% of the normal level of AAT. Individuals of this type who are non smokers usually have only minimal increase in loss of elasticity of the lungs, which is not likely to result in any clinical problem. Smokers, particularly those who smoke heavily, will experience more loss of lung elasticity than normal individuals as their elastin is destroyed. This process occurs more rapidly in MZ individuals will develop clinically apparent lung damage, Chronic obstructive lung disease. Those who have any chronic obstructive lung disease among their relatives should be advised not to smoke if they are of Pi type MZ. The spouse of such individuals should be tested so that any possible Pi type ZZ children can be identified early and warned of the high risk of smoking.
ZZ: About one in 5000 in the normal population. These individuals have very low levels of alpha1-antitrypsin as the abnormal AAT is not released from the liver. They are more susceptible to the development of liver disease in early infancy. They have a high risk for developing chronic obstructive lung disease (emphysema) which can occur in early adulthood. Early detection of such individuals is important. Such individuals should not smoke and should not work in places where there are fumes or other lung irritants.