To date, two variants of argininosuccinic acid lyase deficiency, the second most common enzymatic defect of the urea cycle, have been described. Most of the previous studies reported on outcomes involving neurological and intellectual impairment in affected children. This study is the first to demonstrate that the physical and mental development of such children can be normal and adequate for their age if they are treated with a low-protein diet and/or arginine supplements. Since 1973, 12 Austrian children suffering from argininosuccinic acid lyase deficiency have been detected in the Austrian Neonates Screening Program and could have been followed up. After confirmation of diagnosis, all the children were administered a daily arginine supplement (3 to 4 mmol/kg per day) in conjunction with either a normal diet or a special diet in which protein intake was restricted to 1.2 to 1.5 g/kg per day. Routine checks, including physical examination, determination of biochemical parameters, and IQ tests, were performed so the further development of these 12 patients with respect to treatment could be observed. It can be concluded that early treatment of partial argininosuccinic acid lyase deficiency results in normal intellectual and psychomotor development.