Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Alpha-1-antitrypsin (A1A) is the most abundant serum protease inhibitor and inhibits trypsin and elastin, as well as several other proteases. The release of proteolytic enzymes from plasma onto organ surfaces and into tissue spaces results in tissue damage unless inhibitors are present. Congenital deficiency of A1A is associated with the development of emphysema at an unusually early age and with an increased incidence of neonatal hepatitis, usually progressing to cirrhosis.
See Alpha-1-Antitrypsin-A Comprehensive Testing Algorithm in Special Instructions.
Identification of homozygous and heterozygous phenotypes of the alpha-1-antitrypsin deficiency
There are >40 alpha-1-antitrypsin (A1A) phenotypes (most of these are associated with normal quantitative levels of protein). The most common normal phenotype is M (M, M1, or M2), and >90% of Caucasians are homozygous M (MM) genotype.
A1A deficiency is usually associated with the Z phenotype (ZZ genotype), but genotypes such as SS and SZ are also associated with decreased A1A levels.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This assay does not determine genotype. Genotyping is less variable and more specific than phenotype testing. For genotyping, see A1ATR/83050 Alpha-1-Antitrypsin Deficiency Profile, Mayo's preferred test for diagnosing alpha-1-antitrypsin (A1A) deficiency. A1ATR/83050 includes both A1A quantitation and genotyping; phenotyping is automatically performed when the patient's A1A value and genotype are not diagnostic.
If 2 bands are seen, such as an M band and a Z bands, it is reported as MZ (the equivalent of the genotype).
If 1 band is seen, such as the Z band and the quantitative level is consistent with a homozygote, the phenotype is assumed to be homozygous and is reported as ZZ.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Most normal individuals have the M phenotype (M, M1, or M2). Over 99% of M phenotypes are genotypically MM. In the absence of family studies, the phenotype (M) and quantitative level can be used to infer the genotype (MM). The most common alleles associated with a quantitative deficiency are Z and S. The reports for the rare alleles will indicate whether or not they have been associated with reduced quantitative levels.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
Morse JO: Alpha-1-antitrypsin deficiency. N Engl J Med 1978;299:1045-1048; 1099-1105