Alpha-1-antitrypsin deficiency: a biological enigma.

The association of certain forms of liver disease and a deficiency of alpha-1-antitrypsin is an observation which raises the possibility that other forms of liver disease ultimately will be found to have as their proximate cause a defined metabolic aberration, which may in turn be inherited. Although alpha-1-antitrypsin deficiency is a genetically determined error of protein synthesis, environmental factors, unrecognised at present, are required for the disease to become overt. Thus, this interesting association may herald an increasing number of clinical diseases in which the interaction of environmental stimuli and single genetically determined aberrations are crucially important. The diseases to which we succumb may be largely determined by a genetically determined susceptibility, a point of view which was stated so well by Archibalt Garrod in his essay Inborn Factors in Disease published nearly half a century ago.