Alpha-1 Antitrypsin Deficiency

Alpha-1 antitrypsin deficiency is a genetic disease that can affect the liver and the lungs. It increases the risk of developing emphysema, as many people with this disease develop emphysema as early as their 30s. The disease can also lead to liver problems at birth or later in life, and can cause several other less common problems. Alpha-1 antitrypsin is an important body enzyme. It protects the lungs from damage by another enzyme called elastase, and if it is absent or defective, the lungs are more susceptible to damage, which results in emphysema. Defective alpha-1 antitrypsin not only fails to protect the lungs, it can actually damage the liver. The disease is one of the most common lethal genetic diseases in Caucasians, but because its symptoms can mimic ordinary asthma and emphysema, it is significantly underdiagnosed—many people do not know they have it.[1]

Other names:

Alpha-1 antitrypsin deficiency is sometimes written as α1-antitrypsin deficiency, with the Greek letter α. Common abbreviations include:

• AAT deficiency
• A1AD
• Alpha-1

Types

Alpha-1 antitrypsin is an enzyme, or protein, with an important job to do in the body. The instructions that code for enzymes like this one are called genes, and everyone gets one copy of every gene from each parent (with some exceptions that aren't important here). So everyone has two copies of each gene. The gene for the alpha-1 antitrypsin enzyme is called "Pi," which stands for protease inhibitor, and each person gets a copy of Pi from their mother and a copy from their father. The different types of alpha-1 antitrypsin deficiency are based on how many copies of the Pi gene are defective—one, or both. The normal gene that makes alpha-1 antitrypsin produces a type of alpha-1 antitrypsin called M. A normal person who doesn't have alpha-1 antitrypsin deficiency is referred to as type PiMM. "Pi" refers to the protease inhibitor system, and MM refers to the fact that two normal copies of the gene are producing two normal copies of alpha-1 antitrypsin, each called M.

PiZZ

The most common genetic defect that causes alpha-1 antitrypsin deficiency is the one that produces a type of alpha-1 antitrypsin called Z. Thus, the label of PiZZ refers to a person with two copies of a defective version of the gene, causing all of the antitrypsin that is made to be defective. (Technically, the Z refers to the defective antitrypsin and not to the gene itself.)

PiSZ

This form of alpha-1 antitrypsin deficiency is caused by one copy of a defective gene, Z, and one copy of a nearly normal gene, S. There is still plenty of functional alpha-1 antitrypsin that is made by the S copy. This type of deficiency has not been definitively known to cause disease, but it may be associated with the development of emphysema at a younger age in adulthood than would be expected.

Null genotype

In this type of disease, defective alpha-1 antitrypsin isn't made—in fact, no alpha-1 antitrypsin is made whatsoever. This may be caused by the absence of the gene or a defect in the gene severe enough to not let it function at all to produce any protein. This type is called Pi null/null, or the null genotype. (A genotype is a set of genetic information.) This type of alpha-1 antitrypsin deficiency has the typical lung problems but no liver problems, since defective alpha-1 antitrypsin hurts the liver, and in this disease there is no defective alpha-1 antitrypsin to cause that damage.

Carriers

Other types, such as PiMS or PiMZ, generally don't cause the disease. People with PiMZ are considered to be carriers of the disease, though. If both the mother and the father are carriers, then, on average, one-fourth of their children will have the full-blown disease. Carriers generally make about 40&–60% of the normal amount of alpha-1 antitrypsin. This quantity is sufficient to not cause any damage to the lungs and liver. However, there is some evidence that being a carrier increases the risk of lung[2] or liver cancer.[3]

Note on terminology

The terminology refers to the types of proteins detected by the blood test used to detect this disease. The actual gene itself is not detected. So, these types are technically phenotypes (which refers to an organism's characteristics), not genotypes (which refers to an organism's genes). (For more information on the difference between a genotype and a phenotype, click here.)