1 Department of Pediatrics, New York University Medical Center, New York
SYMPTOMS
All of the defects of the urea cycle may result in the accumulation of ammonia. This is manifested clinically by episodes of vomiting, lethargy, seizures, coma, and ultimately in death if the hyperammonemia is not controlled. In older children these symptoms may be preceded by a period of irritability and hyperactivity. It has usually been considered that the severity of the hyperammonemia depends on the site of the block; the nearer it is to ammonia, the greater the accumulation. There are, however, exceptions, as hyperammonemia leading to neonatal death has been observed in arginino-succinate lyase deficiency,39,40 the fourth step in the cycle. Death due to hyperammonemia has been observed in all the defects except arginase deficiency.41-43 There are variations in the severity of the clinical course of all of these syndromes; the exact reason for this has not been ascertained, although it is quite possible that this is related to the degree of residual enzyme activity. Thus, carbamylphosphate synthetase deficiency has been associated both with death in the newborn period or survival without specific treatment but with physical and mental retardation for a number of years.42-44
The clinical features of ornithine transcarbamylase deficiency have been the most completely described.45,46 As this anomaly is inherited as a sexlinked dominant, males are most severely affected, and neonatal death has been almost universal.13 Males who have survived without the most vigorous treatment have had a variant of the disease,47,48 the enzyme having different kinetic properties. Females who have various degrees of residual enzyme activity usually do not manifest symptoms until sometime after the neonatal period, often in response to some stress.