MOST, if not all, of congenital metabolic disease may be attributed to abnormalities in protein synthesis. An error in protein synthesis can result in at least two basic types of disturbance—an actual deficit of a specific protein, or the production of abnormal forms of that protein. Because of the wide variety of functions of this class of substances, the result may manifest itself as a disturbance in the metabolism of fats, carbohydrates or amino acids, or a disturbance of protein interactions.
While the clinical manifestations of some disorders may be related directly to the deficit of a specific protein, in others symptoms are related indirectly to a specific protein deficiency (Fig. 1). This is particularly true in those instances where the protein, which is deficient, acts as an enzyme in intermediary metabolism, and the symptoms of disease may be due either to an accumulation or a deficit of specific metabolites or electrolytes. In still other instances, clinical disease is related not to the absence of a normal protein but to the presence of an abnormal protein which does not function in the same way as its normal analogue.
It is not the purpose of this paper to discuss all the inborn errors of protein metabolism, but to give a brief account of some examples to illustrate the fundamental importance of protein synthesis to human health.
Afibrinogenemia, a hemorrhagic diathesis associated with the absence of fibrinogen in the blood and a clotting time of infinity, was recognized as early as 1920. Since that time a number of children with this disorder have been described and, in a review by Diamond, Wolff and Borges, 19 cases, including 3 observed by these authors, are reported.