Signs and symptoms
Individuals with A1AD may develop chronic obstructive pulmonary disease (emphysema) 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. 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.
Four percent of them carry the PiZ allele; between 1 in 625 and 1 in 2000 are homozygous.Another study detected a frequency of 1 in 1550 individuals. The highest prevalence of the PiZZ variant was recorded in the northern and western European countries with mean gene frequency of 0.0140. Worldwide, an estimated 1.1 million people have A1AT deficiency and roughly 116 million are carriers of mutations.A1AD is one of the most common genetic diseases worldwide and the second most common metabolic disease affecting the liver. History
A1AD was discovered in 1963 by Carl-Bertil Laurell (1919–2001), at the University of Lund in Sweden. Laurell, along with a medical resident, Sten Eriksson, made the discovery after noting the absence of the α1 band on protein electrophoresis in five of 1500 samples; three of the five patients were found to have developed emphysema at a young age.The link with liver disease was made six years later, when Harvey Sharp et al. described A1AD in the context of liver disease. Research
Recombinant and inhaled forms of A1AT are being studied. References
External links

Alpha-1-antitrypsin deficiency on Orphanet