Alpha-1 Antitrypsin Deficiency, or Alpha-1, is an inherited, genetic condition that is passed on from generation to generation.
In order to be classified as having Alpha-1, an individual must inherit at least one abnormal AATalpha-1 antitrypsin More gene. Individuals who have one abnormal AATalpha-1 antitrypsin More gene and one normal AATalpha-1 antitrypsin More gene are sometimes referred to as heterozygotes or “carriersAn Alpha-1 Carrier is a person who has one normal ATT gene (M) and one defective AAT gene (usually S or Z). It does NOT mean you cannot get sick. More.”
Many of the risk factors that can lead to disease in Alphas are known, and the management of these risk factors is one of the most important ways in which individuals with Alpha-1 can directly affect the quality of their lives. Recently, there has been a growing appreciation that individuals who have been identified as carriersAn Alpha-1 Carrier is a person who has one normal ATT gene (M) and one defective AAT gene (usually S or Z). It does NOT mean you cannot get sick. More of the Alpha-1 gene also may be at increased risk for disease development. Therefore, limiting exposure to environmental risk factors is important for these individuals as well.
The severity of Alpha-1 is a function of the type of abnormal Alpha-1 genes inherited. Under a system called “Pi-typing,” numerous types of AATalpha-1 antitrypsin More genes have been identified and named, allowing for each type to be studied and evaluated. For example, the AATalpha-1 antitrypsin More genes Z and Null represent two Pi-types that are often associated with severe AATalpha-1 antitrypsin More deficiencies. Another type of AATalpha-1 antitrypsin More gene, the F Pi-type, produces a form of Alpha-1 in which the amount of AATalpha-1 antitrypsin More in the blood is normal, but the AATalpha-1 antitrypsin More does not perform properly. Interestingly, there also are abnormalities of the AATalpha-1 antitrypsin More gene that do not affect either the blood levels of the AATalpha-1 antitrypsin More protein or how the AATalpha-1 antitrypsin More functions.
Introduction to Alpha-1 – Big Fat Reference Guide
The gene for α1-AT is located on chromosome 14, and mutations at the protease inhibitor (PI) locus lead to a single amino acid substitution (glutamic acid for lysine 342) that impairs secretion of the mutant gene product, leading to retention of α1-AT in the hepatocyte and low levels of α1-AT in the serum. Because the phenotype is expressed by autosomal codominant
Alpha1-Antitrypsin Deficiency – Cleveland Clinic"Individuals receive one version of a gene, called an allele, from each parent. If the alleles are different, the dominant allele usually will be expressed, while the effect of the other allele, called recessive, is masked. In codominance, ... More inheritance, each allele is responsible for 50% of the circulating α1-AT level. Approximately 100 allelic variants have been described, only some of which are associated with liver disease.
Resources
- Alpha-1 Genetic Counseling Program – Alpha-1 Foundation
- Alpha-1 Alleles Website – AlphaNet
- Novel Alpha-1 Antitrypsin Alleles and Alpha-1-Antitrypsin Deficiency Detection – Dr. Mark Brantly, 28th Annual Alpha-1 National Conference, June 2019