Alpha-1 antitrypsin deficiency

Alpha-1 antitrypsin deficiency is an inherited disorder that can cause lung disease in adults and liver disease in adults and children.

The first signs of lung disease caused by alpha-1 antitrypsin deficiency usually appear between ages 20 and 40. The earliest symptoms are shortness of breath following mild activity, reduced ability to exercise, and wheezing. Other symptoms can include unintentional weight loss, recurring respiratory infections, fatigue, a barrel-shaped chest, rapid heartbeat upon standing, and vision abnormalities. Smoking or exposure to tobacco smoke accelerates the appearance of symptoms and damage to the lungs.

About 10 percent of infants and 15 percent of adults also have liver damage caused by alpha-1 antitrypsin deficiency. Symptoms of liver disease can include a swollen abdomen, coughing up blood, swollen feet or legs, and yellowing of the skin and whites of the eyes (jaundice).

In rare cases, alpha-1 antitrypsin deficiency also causes a skin condition known as panniculitis, which is characterized by hardened skin with painful lumps or patches. Panniculitis varies in severity and can occur at any age.

Worldwide, approximately 1 in 2,500 individuals has alpha-1 antitrypsin deficiency. While this disorder is found in all ethnic groups, it occurs most frequently in whites of European ancestry.

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

The SERPINA1 gene produces a protein called alpha-1 antitrypsin, which protects the body from being damaged by a powerful enzyme contained in white blood cells. This enzyme is released from white blood cells to fight infection, but it can attack normal tissues (such as the lungs) if not carefully controlled by alpha-1 antitrypsin. A mutation in the SERPINA1 gene can result in a missing alpha-1 antitrypsin protein or an abnormal protein that cannot control the white blood cell enzyme. The abnormal protein can also accumulate in the liver and may damage this organ.

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), called M, produces normal levels of the alpha-1 antitrypsin protein. Most people have two copies of the M allele (MM), one from each parent. Two altered versions that produce moderately low or very low levels of alpha-1 antitrypsin are called S and Z, respectively. Individuals with two copies of an altered allele (ZZ or SZ) are likely to develop alpha-1 antitrypsin deficiency.

Worldwide, about 116 million people carry a copy of the S or Z allele. Individuals with a MS or SS combination usually produce enough alpha-1 antitrypsin to protect the lungs. Carriers with the MZ alleles, however, have an increased risk for lung disease, particularly if they smoke.

You may find the following resources about alpha-1 antitrypsin deficiency helpful.

• MedlinePlus - Health Information (4 links)
• Genes and Disease - Genetic disorder summaries
• Educational resources - Information pages (2 links)
• Patient support - For patients and families (4 links)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

• Gene Tests - DNA tests ordered by healthcare professionals
• ClinicalTrials.gov - Linking patients to medical research
• PubMed - Recent literature
• OMIM - Genetic disorder catalog

See How are genetic conditions and genes named? in the Handbook.

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These links provide additional genetics resources that may be useful.

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allele ; autosomal ; carrier ; codominance ; connective tissue ; deficiency ; emphysema ; enzyme ; expressed ; gene ; infection ; jaundice ; mutation ; protein ; pulmonary ; pulmonary emphysema ; respiratory ; sign ; symptom ; white blood cells

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.