a1-Antitripsin Deficiency

a1-antitrypsin is a glycoprotein synthesized in the liver that plays a key role in the modulation of inflammatory reactions by inhibiting acute phase proteins, expecially neutrophil elastase. a1-antitrypsin deficiency is a disease that affects Caucasians, characterized by liver disease in children and emphysema in adults, with a frequency of 1 per 2000 to 7000 newborns &. It was first described by Freier and colleagues in 1968 &, and by Sharp et al in 1969 &, and well described by Sveger &.
Alpha1- antitrypsin deficiency is caused by a defect of the Protease inhibitor (Pi) gene, located on chromoseme 14, with codominant expression of the two inherited alleles. About 75 different allelic variants are known &, some of which are associated with the disease. The normal phenotype is PiMM, while the PiZZ phenotype is associated with abnormally low levels of a1-antitrypsin and with hepatic or pulmonary disease &. Other variants (eg, PiMZ, PiMS) have been described &.
The pathogenesis of the liver and pulmonary manifestations of the disease is different: in the lung the unopposed action of neutrophil elastase causes destruction of lung parenchyma with emphysema &; the liver disease is the result of accumulation of abnormal globules of a1-antitrypsin, typically periodic acid-Schiff-positive and diastase resistant, in periportal lymphocytes &.
Most individuals with hepatic dysfunction have a neonatal history of cholestasis. In these patients liver dysfunction resolves spontaneously in 25% of the cases, while another 25% evolve into progressive hepatic failure, and in the remaining 50% develop persistent liver disease.
The possibility to cure a1-antitrypsin deficiency was first reported in 1973 &, demonstrating a1-antitrypsin serum level normalization, and conversion of the recipient’s phenotype to that of the donor. After that liver transplantation has become the treatment of choice for a1-antitrypsin deficiency, with excellent outcomes, and with no patients to date having developed emphysema.