A VARIANT OF CARNOSINEMIA WITH NORMAL SERUM CARNOSINASE ACTIVITY IN AN INFANT

The six week old son of a first cousin marriage presented with hyperammonemia, transient acidosts, hepatosplenomegaly, failure to thrive, and seizures. Quantitative plasma and urine amino acids, including lysine clearance, were normal, orotic acid excretion was not increased, and no organic acid abnormalities were evident by GLC-mass spectroscopic analysis. Notably, during periods when the patient was placed on a diet containing 1 gm/kg/day protein intake, arginine supplementation (100 mgm/kg/day) consistently and significantly lowered plasma ammonia (on arginine, 82 μgm% ± 3, S.E.; off arginine, 113 ± 8; p < .01). The mean value for plasma ammonia during periods on a 2gm/kg/day protein diet without arginine (80 ± 17) was lower than on 1 gm/kg/day protein (p=0.1). Liver biopsy was examined by light and electron microscopy. Enzymes of the urea cycle were assayed by Dr. P. J. Snodgrass, revealing a partial deficiency of CPS (0.49 μmol/mg prot/hr; normal neonatal mean 1.13, range 0.81-1.41), assayed in the presence of excess N-acetylglutamate. Since arginine activates glutamate N-acetylase and N-acetylglutamate produced by this reaction is a cofactor for CPS, we postulate that arginine, supplied as such or through moderate amounts of dietary protein, lowered plasma ammonia in our patient by stimulating residual CPS activity.