Urea-Cycle Enzyme Deficiencies and an Increased Nitrogen Load Producing Hyperammonemia in Reye's Syndrome

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Abstract
Assay of urea-cycle enzymes in liver tissue showed ornithine transcarbamylase activities of 18 to 72 per cent of the normal mean in eight patients with Reye's syndrome, below the range of normal in seven of eight, and, in six cases, as low as those in females with X-linked deficiency of this enzyme. Carbamyl phosphate synthetase activities were less than 32 per cent of controls in two patients. Argininosuccinate synthetase and lyase activities were normal in seven patients. Arginase was normal in two biopsy specimens, but below normal in four of five autopsy specimens. The Km's for ornithine and carbamyl phosphate, pH optimum, and heat lability of ornithine transcarbamylase were normal. Two patients excreted 0.64 and 0.58 g per kilogram per day of urinary nitrogen at the peak of hyperammonemia, in spite of peritoneal dialysis. The hyperammonemia of Reye's syndrome apparently results from excess waste nitrogen that overwhelms the ability of reduced ornithine transcarbamylase (and occasionally carbamyl phosphate synthetase) to detoxify the ammonia load. (N Engl J Med 294:855–860, 1976)