Introduction to Urea Cycle Symposium

Abstract

When Donough O'Brien reviewed the field of metabolic diseases in 1965, he discussed disorders implicating carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC), argininosuccinic acid (ASA) synthetase, and argininosuccinic acid lyase. Arginase defects had not yet been encountered. Several cases of argininosuccinic aciduria had been reported, but only single cases of CPS, OTC, and ASA synthetase defects had been described. The succeeding 15 years have seen much progress in this field, much of it reflecting the efforts of individuals participating in this program. My first contact with disorders of the urea cycle was in 1976 when a suspected OTC deficiency in a female infant was identified by Dr Kenneth Shaw, for a colleague of ours at the University of Southern California Medical Center. I was asked to help with the care of that infant, who died many months later of meningitis. Largely due to Ken's indefatigable efforts in screening high-risk infants for metabolic diseases, we have seen various urea cycle defects identified in several other infants. However, we have sometimes encountered the unexpected in attempting to confirm the clinical diagnosis by enzyme analysis. The following comments on two patients exemplify the situation. Patient C.S. was in a coma on admission; his blood ammonia level was 895 µg/100 ml. Urinary orotic acid levels were elevated and our clinical impression was that the patient had a variant of an OTC defect. Analysis of the liver biopsy specimen revealed 35% CPS, 42% OTC, 24% ASA synthetase, 100% ASA lyase, and 31% arginase. Patient N.G. was born in a nearby medical center and shortly thereafter became lethargic, vomited, and lapsed into a coma.