Lethal Neonatal Deficiency of Carbamyl Phosphate Synthetase

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Abstract
A male infant, who appeared normal at birth, manifested hypothermia, irritability, and hypertonia 24 hours after beginning protein feedings. Increasing rigidity and coma ensued, and the child died at 75 hours of age. A male sibling had also died with an identical clinical picture. Laboratory studies on the proband demonstrated a blood ammonia of 1480 μg per 100 ml (normal <150 μg per 100 ml). Assay of the urea-cycle enzymes in liver obtained at autopsy revealed selective deficiency of carbamyl phosphate synthetase activity (<10 per cent of the lowest newborn autopsy control); activity of the other four urea-cycle enzymes was normal. The residual carbamyl phosphate synthetase activity was not dependent on N-acetylglutamate, suggesting that it represented cytoplasmic carbamyl phosphate synthetase II, and that mitochondrial carbamyl phosphate synthetase I was completely absent. Deficiency of this enzyme must now be added to the causes of lethal hyperammonemia in the newborn. (N Engl J Med 290:430–433, 1974)