Alpha-1 antitrypsin deficiency
Alpha-1 antitrypsin deficiency (A1AD or AATD) is a genetic disorder that may result in lung disease or liver disease. Onset of lung problems is typically between 20 and 50 years of age. This may result in shortness of breath, wheezing, or an increased risk of lung infections. Complications may include chronic obstructive pulmonary disease (COPD), cirrhosis, neonatal jaundice, or panniculitis.
| Alpha-1 antitrypsin deficiency | |
|---|---|
| Other names | α1-antitrypsin deficiency |
| Structure of Alpha-1 antitrypsin | |
| Specialty | Pulmonology, Hepatology, Medical genetics |
| Symptoms | Shortness of breath, wheezing, yellowish skin |
| Complications | COPD, cirrhosis, neonatal jaundice, panniculitis |
| Usual onset | 20 to 50 years old |
| Causes | Mutation in the SERPINA1 gene |
| Risk factors | Northern European and Iberian ancestry |
| Diagnostic method | Based on symptoms, blood tests, genetic tests |
| Differential diagnosis | Asthma |
| Treatment | Medications, lung transplant, liver transplant |
| Medication | Bronchodilators, inhaled steroids, antibiotics, intravenous infusions of A1AT protein |
| Prognosis | Life expectancy ~50 years (smokers), nearly normal (non-smokers) |
| Frequency | 1 in 2,500 (Europeans) |
A1AD is due to a mutation in the SERPINA1 gene that results in not enough alpha-1 antitrypsin (A1AT). Risk factors for lung disease include tobacco smoking and environmental dust. The underlying mechanism involves unblocked neutrophil elastase and buildup of abnormal A1AT in the liver. It is autosomal co-dominant, meaning that one defective allele tends to result in milder disease than two defective alleles. The diagnosis is suspected based on symptoms and confirmed by blood tests or genetic tests.
Treatment of lung disease may include bronchodilators, inhaled steroids, and, when infections occur, antibiotics. Intravenous infusions of the A1AT protein or in severe disease lung transplantation may also be recommended. In those with severe liver disease liver transplantation may be an option. Avoiding smoking is recommended. Vaccination for influenza, pneumococcus, and hepatitis is also recommended. Life expectancy among those who smoke is 50 years while among those who do not smoke it is almost normal.
The condition affects about 1 in 2,500 people of European descent. Severe deficiency occurs in about 1 in 5,000. In Asians it is uncommon. About 3% of people with COPD are believed to have the condition. Alpha-1 antitrypsin deficiency was first described in the 1960s.