Citrullinemia: phenotypic variations

Abstract

An 18-month-old female infant was found to have citrullinemia on routine plasma screening by the Scriver Method at 5 days of age. At 10 days of age, plasma citrulline concentration was 0.704mumol/ml (normal, 0.010 to 0.030mumol/ml) and has remained 60 to 80 times higher than normal. Urine citrulline concentration was markedly elevated. Hyperammonemia occurred at 1 month of age. The serum ammonia concentration was 473mug/100 ml (normal, 50 to 250 mug/100 ml) and rose to 770mug/100 ml at 4 months of age. Dietary protein was restricted to 1.6 gm/kg/day. Without further change in protein intake, the serum ammonia concentration decreased to 280mug/100 ml and, since then, it has returned to normal. The addition of three synthetic L-amino acids was required for a short time during dietary therapy. At 10 months of age, the infant was given a normal diet. At 18 months of age, her physical and mental development is normal. Activity of argininosuccinic acid synthetase measured in skin fibroblasts was 0.0037mumol of radioactive carbon dioxide per milligram of protein per hour. To demonstrate heterozygosity, fasting plasma citrulline concentrations were measured in five members of the family. Comparison of findings in this patient with those reported in the literature suggests phenotypical variation of the disease, probably due to genetic heterogeneity.