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Twenty-four cases of type II citrullinemia, diagnosed as such based on enzymatic analysis showing a decreased enzyme content of kinetically-normal argininosuccinate synthetase in the liver, showed the following features of their serum amino acid patterns: 1) Serum arginine levels were higher than in controls and were significantly correlated with serum citrulline levels. 2) Serum alanine, serine, glycine, and branched-chain amino acids (valine+isoleucine+leucine) were significantly lower than in the controls, while threonine was rather higher and aromatic amino acids (tyrosine+phenylalanine) remained at the control level. Thus the ratio of threonine to serine and of branched-chain amino acids to aromatic amino acids were characteristically higher and lower than the control values, respectively.The above characteristics were quite unique to type II citrullinemia and not found in serum amino acid patterns of type I and III citrullinemic patients. Examination of effect of oral administration of citrulline on the amino acid pattern was also showed that the decrease of serum citrulline after the administration was delayed in type II citrullinemic patients; which was, however, not specific to type II citrullinemia, but was also found in patients with liver cirrhosis and chronic nephritis, and more prominently in one type III citrullinemic patient. After citrulline administration, serum arginine was increased in type II citrullinemic patients as much as in the healthy controls, but was decreased in the type III patient. The increase in serum ornithine after citrulline administration in the type II patients and in the parents of the type III patient (considered to be heterozygotes) was about half of the control value, but that in patients with liver cirrhosis was greater than the control. The ratios of threonine to serine and branched-chain amino acids to aromatic amino acids were not altered by the citrulline administration.

Serum Amino Acid Pattern of Type II Citrullinemic Patients and Effect of Oral Administration of Citrulline