Arginase deficiency in multiple tissues in argininemia

Abstract

A 5 9/12 yr old Mexican female with argininemia presented at 4 yr of age with severe growth retardation, microcephaly, mental retardation, loss of ability to walk, spasticity and epileptiform electroencephalogram. At follow-up, blood ammonia was elevated only twice out of 30 determinations. Blood arginine was 544-1074 .mu.mol/l (normal 61 to 173); cerebrospinal fluid arginine was 88 .mu.mol/l (normal 6-29); and urinary arginine, citrulline and argininosuccinic acid were consistently elevated. Arginase activities in tissues from the propositus were 0.01 mU/mg Hb in erythrocytes (normal 29.8 to 96.1); 9 mU/mg protein in liver (normal 1522 to 5491); and 5 mU/mg protein in stratum corneum (normal 2856-7556). The demonstration of arginase deficiency in liver and stratum corneum suggests a generalized deficiency and helps to explain the elevation of blood arginine. Therapeutic trials of orally administered lysine to enhance dibasic amino acid competition and of enzyme replacement using erythrocyte transfusion did not result in significantly decreased blood arginine or clinical improvement.