Use of EnzymeIoaded Erythrocytes in In-Vitro Correction of Arginase-Deficient Erythrocytes in Familial Hyperargininernia

The capacity of arginase-deficient erythrocytes of pa-tients with familial hyperargininemia to produce urea and to catabolize arginine can be increased in vitro by introducing human liver arginase into their erythrocytes. The results of this study on a specific human model show that it is possible to change the metabolic func-tion of a genetically defective erythrocyte by incorpo-rating exogenous human enzyme. The in vivo applica-tion of enzyme-loaded erythrocytes for enzyme re-placement therapy of inborn metabolic errors in hu-mans must await in vivo studies on animal models. Additional Keyphrase: potential enzymic therapy of certain inherited disorders Familial hyperargininemia with arginase deficien-cy of erythrocytes is an inborn error of the urea cycle described in only two families (1, 2). Arginase (EC 3.5.3.1) catalyzes the conversion of arginine to orni-thine and urea. Clinically, the disease is character-ized by mental retardation, spastic paralysis, sei-zures, ataxia, tremor, and periodic vomiting. Impor-tant biochemical abnormalities are high plasma con-centrations of arginine and ammonia and a secondary cystinuria/lysinuria (3). Proteins (4, 5) and enzymes (6) can be introduced into erythrocytes during hypotonic hemolysis. Using these techniques, we loaded normal human erythro-cytes and arginase-deficient erythrocytes from two patients with arginase deficiency and one obligate heterozygote with exogenous arginase and we com-pared the capacity to produce urea and to catabolize arginine of these arginase-loaded erythrocytes with that of the original erythrocytes. Potential therapeu-tic implications of some inborn errors of metabolism are proposed in terms of this model