alpha-1 antitrypsin deficiency 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 deficiencyother namesα1-antitrypsin deficiencystructure of alpha-1 antitrypsinspecialtypulmonology, hepatology, medical geneticssymptomsshortness of breath, wheezing, yellowish skincomplicationscopd, cirrhosis, neonatal jaundice, panniculitisusual onset20 to 50 years oldcausesmutation in the serpina1 generisk factorsnorthern european and iberian ancestrydiagnostic methodbased on symptoms, blood tests, genetic testsdifferential diagnosisasthmatreatmentmedications, lung transplant, liver transplantmedicationbronchodilators, inhaled steroids, antibiotics, intravenous infusions of a1at proteinprognosislife expectancy ~50 years (smokers), nearly normal (non-smokers)frequency1 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. signs and symptoms individuals with a1ad may develop emphysema, or chronic obstructive pulmonary disease during their thirties or forties even without a history of smoking, though smoking greatly increases the risk. symptoms may include shortness of breath (on exertion and later at rest), wheezing, and sputum production. symptoms may resemble recurrent respiratory infections or asthma. a1ad may cause several manifestations associated with liver disease, which include impaired liver function and cirrhosis. in newborns, alpha-1 antitrypsin deficiency can result in early onset jaundice followed by prolonged jaundice. between 3% and 5% of children with zz mutations develop life-threatening liver disease, including liver failure. a1ad is a leading reason for liver transplantation in newborns. in newborns and children, a1ad may cause jaundice, poor feeding, poor weight gain, hepatomegaly and splenomegaly. conditions associated with alpha-1 antitrypsin deficiency, occurring due to paucity of aat in circulation allowing uninhibited inflammation in lungs, and accumulation of mutated aat in the liver apart from copd and chronic liver disease, α1-antitrypsin deficiency has been associated with necrotizing panniculitis (a skin condition) and with granulomatosis with polyangiitis in which inflammation of the blood vessels may affect a number of organs but predominantly the lungs and the kidneys. genetics serpin peptidase inhibitor, clade a, member 1 (serpina1) is the gene that encodes the protein alpha-1 antitrypsin. serpina1 has been localized to chromosome 14q32. over 75 mutations of the serpina1 gene have been identified, many with clinically significant effects. the most common cause of severe deficiency, piz, is a single base-pair substitution leading to a glutamic acid to lysine mutation at position 342 (dbsnp: rs28929474), while pis is caused by a glutamic acid to valine mutation at position 264 (dbsnp: rs17580). other rarer forms have been described . pathophysiology photomicrograph of a liver biopsy from a patient with alpha-1 antitrypsin deficiency. the pas with diastase stain shows the diastase-resistant pink globules that are characteristic of this disease.