Alpha-1-antitrypsin deficiency: an overview of recent advances

ABSTRACT

Alpha 1-antitrypsin [alpha1 AT], a serpine, is one of the most important proteinase inhibitor in the serum and plays an essential role in protection of the lung tissues against the proteolytic attach of elastase. The gene for alpha1 AT is located on chromosome 14 q 32 and is highly susceptible to mutations. A large number of variants of alpha1 AT are known and some including PiZ and PiS result in alpha1 AT deficiency. In patients with PiZ, the most severe and common alpha1 AT deficient variant, the alpha1 AT protein accumulates in the liver and results in severe hepatic diseases. Other clinical consequences of alpha1 AT deficiency include emphysema in majority of the patients. This state is further aggravated in patients who smoke. Several treatment strategies have been suggested, including replacement therapy by purified alpha1 AT or recombinant alpha1 AT given intravenously or as aerosol. Synthetic peptides, lung transplantation and volume reduction surgery are under investigation and evaluation. This paper updates the information on alpha1 AT and its deficiency state