Alpha-1 antitrypsin deficiency

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[1]
Complications	COPD, cirrhosis, neonatal jaundice, panniculitis[1]
Usual onset	20 to 50 years old[1]
Causes	Mutation in the SERPINA1 gene[1]
Risk factors	Northern European and Iberian ancestry
Diagnostic method	Based on symptoms, blood tests, genetic tests[2]
Differential diagnosis	Asthma[1]
Treatment	Medications, lung transplant, liver transplant[2]
Medication	Bronchodilators, inhaled steroids, antibiotics, intravenous infusions of A1AT protein[2]
Prognosis	Life expectancy ~50 years (smokers), nearly normal (non-smokers)[3]
Frequency	1 in 2,500 (Europeans)[1]

Alpha-1 antitrypsin deficiency (A1AD or AATD) is a genetic disorder that may result in lung disease or liver disease.^[1] Onset of lung problems is typically between 20 and 50 years of age.^[1] This may result in shortness of breath, wheezing, or an increased risk of lung infections.^[1][2] Complications may include chronic obstructive pulmonary disease (COPD), cirrhosis, neonatal jaundice, or panniculitis.^[1]

A1AD is due to a mutation in the SERPINA1 gene that results in not enough alpha-1 antitrypsin (A1AT).^[1] Risk factors for lung disease include tobacco smoking and environmental dust.^[1] The underlying mechanism involves unblocked neutrophil elastase and buildup of abnormal A1AT in the liver.^[1] It is autosomal co-dominant, meaning that one defective allele tends to result in milder deficiency than two defective alleles; for example, carriers with an MS (or SS) allele combination usually produce enough alpha-1 antitrypsin to protect the lungs, while those with MZ alleles have a slightly increased risk of impaired lung or liver function.^[1] The diagnosis is suspected based on symptoms and confirmed by blood tests or genetic tests.^[2]

Treatment of lung disease may include bronchodilators, inhaled steroids, and, when infections occur, antibiotics.^[2] Intravenous infusions of the A1AT protein or in severe disease lung transplantation may also be recommended.^[2] In those with severe liver disease liver transplantation may be an option.^[2][4] Avoiding smoking is recommended.^[2] Vaccination for influenza, pneumococcus, and hepatitis is also recommended.^[2] Life expectancy among those who smoke is 50 years while among those who do not smoke it is almost normal.^[3]

The condition affects about 1 in 2,500 people of European descent.^[1] Severe deficiency occurs in about 1 in 5,000.^[5] In Asians it is uncommon.^[1] About 3% of people with COPD are believed to have the condition.^[5] Alpha-1 antitrypsin deficiency was first described in the 1960s.^[6]