Alpha 1 Antitrypsin Deficiency (cont.)

How common is alpha-1 antitrypsin deficiency?

Alpha-1 antitrypsin deficiency occurs worldwide, but its prevalence varies by population. For example, this disorder affects 1 in 1,500 to 3,000 individuals with European ancestry, but it is less common in Asian and black populations.

What genes are related to alpha-1 antitrypsin deficiency?

Mutations in the SERPINA1 gene cause alpha-1 antitrypsin deficiency.

The SERPINA1 gene provides instructions for making a protein called alpha-1 antitrypsin. This protein protects the body from being damaged by a powerful enzyme called neutrophil elastase. Neutrophil elastase is released from white blood cells to fight infection, but it can attack normal tissues (such as lung tissue) if not carefully controlled by alpha-1 antitrypsin. Mutations in the SERPINA1 gene can lead to a shortage (deficiency) of alpha-1 antitrypsin protein or an abnormal form of the protein that cannot control neutrophil elastase. Uncontrolled, neutrophil elastase destroys alveoli, which can lead to emphysema. The abnormal form of alpha-1 antitrypsin can also accumulate in the liver and may damage this organ.

How do people inherit alpha-1 antitrypsin deficiency?

This condition is inherited in an autosomal codominant pattern. Codominance means that two different versions of the gene may be expressed, and both versions contribute to the genetic trait.

The most common version (allele) of the SERPINA1 gene, called M, produces normal levels of the alpha-1 antitrypsin protein. Most people have two copies of the M allele (MM) in each cell. Other versions of the SERPINA1 gene lead to reduced levels of alpha-1 antitrypsin. For example, the S allele produces moderately low levels of this enzyme, and the Z allele produces very little alpha-1 antitrypsin. Individuals with two copies of the Z allele (ZZ) in each cell are likely to have alpha-1 antitrypsin deficiency. Those with the SZ combination have an increased risk of developing lung disorders (such as emphysema), particularly if they smoke.

Worldwide, about 161 million people have one copy of the S or Z allele and one copy of the M allele in each cell (MS or MZ). Individuals with a MS (or SS) combination usually produce enough alpha-1 antitrypsin to protect the lungs. People with MZ alleles, however, have a slightly increased risk of impaired lung or liver function.

Medically Reviewed by a Doctor on 4/1/2014

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