Alpha-1 Antitrypsin Deficiency

Alpha-1 Antitrypsin Deficiency

Although Alpha-1 is one of the most common genetic disorders in the world, it is often misdiagnosed. Many times patients are told they have asthma, bronchitis, symptoms related to stress, emphysema caused by smoking, or simply chronic obstructive pulmonary disease of unknown cause.

There are different types of tests for Alpha-1. One laboratory test measures alpha-1 antitrypsin levels in the blood, which can be reported in two different units of measurement: milligrams per deciliter (mg/dL) or micromoles (µM). Both measurements provide the same basic information on how much alpha-1 antitrypsin is in the blood. 

People with two normal copies of the alpha-1 gene produce the most alpha-1 antitrypsin, and people with two deficiency copies of the gene produce the least. In addition, environmental factors can affect how much alpha-1 antitrypsin is in the blood. Here are the more common genotypes and their corresponding blood alpha-1 levels.

Genotype µM mg/dl
MM (two normal copies) 20-48 150-350
MZ (one normal copy, one deficient copy) 17-33 90-210
SS (two marginally deficient copies) 15-33 100-200
SZ (one deficient copy, one marginally deficient copy) 8-16 75-120
ZZ (two deficient copies) 2.5-7 20-45
NULL (two nonfunctional copies) 0 0


Alpha-1 levels of 11 µM or less put you at greatest risk of developing alpha-1 related lung disease. Smokers with intermediate deficiency levels (17-33 µM) are also at increased risk of lung disease.

 In the table above, M refers to the normal allele. Over 100 alleles, forms of the gene for Alpha-1, have been identified, some of which can cause Alpha-1. The S and Z alleles are the most common ones that cause alpha-1 deficiency. ZZ is severe deficiency of alpha-1 and is associated with lung disease.

The Null alleles are ones that produce no detectable levels of alpha-1. Alphas with the Null-Null genotype are at the greatest risk of developing lung disease; however, they may not have the same risk for liver disease as an individual that is ZZ.

Augmentation Therapy

Augmentation therapy consists of weekly IV infusions of alpha-1 antitrypsin derived from human plasma. It is used to increase the concentration of the protein in the blood and lungs. Augmentation therapy is the only FDA-approved treatment for alpha-1 antitrypsin deficiency.  Your lung specialist can determine if you are an appropriate candidate for such therapy, which is covered by most insurance plans.

Drug Therapy

This is among the most important types of medical therapy for the newly diagnosed individual with Alpha-1 Antitrypsin Deficiency. Although these are most relevant to lung-affected individuals, remember all Alphas have risks to their lungs. Some of the therapies listed are relevant for all patients with Alpha-1.

Surgical Options

Lung/liver transplantation can be a viable option for some patients. As experience with new surgical techniques increases (particularly single-lung transplantation), lung transplantation may become more attractive to patients with Alpha-1 with end-stage lung disease. Also, living-related liver transplantation is an option at some transplant facilities.

Transplantation is only for patients with end-stage lung or liver disease, which means that they are resistant to more conservative therapies (such as treating symptoms or augmentation therapy). Patients must have extensive damage in the lungs or liver to warrant this surgical option.