Argininosuccinic Aciduria: An Inborn Error of Amino Acid Metabolism

Abstract

An infant who had, in the first week of life, a sudden onset of severe illness with abdominal distension, gross liver enlargement, blood-stained vomiting and a period of unconsciousness, was found to be excreting large amounts of argininosuccinic acid (ASA), an intermediate compound in the biosynthesis of urea. His subsequent history has been of mental and physical retardation, persistent liver enlargement, skin lesions and episodes of convulsions, or loss of consciousness. The clinical features of the present case are compared with those of the two previously reported cases in one family (Allan et al., 1958). An identical hair anomaly was found in all three cases. The level of ASA in the cerebrospinal fluid was higher than that in the plasma, whilst the blood urea was normal. Reduction of protein intake apparently resulted in the reduction of ASA formation, and addition of arginine to the food gave increased ASA excretion. Although the accumulation of ASA in the cerebrospinal fluid and a blood urea within the normal range might be explained by a genetic deficiency of argininosuccinase in the urea cycle in the brain, this postulate would necessitate a genetic defect in the cells of only one organ, other cells being normal.