Chapter 35 - Urea cycle disorders

Summary

The clinical manifestations of Urea cycle disorders are the result of acute or chronic hyperammonemia and include acute neurologic and gastrointestinal symptoms and signs. Chronic hyperammonemia may induce changes in N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission and induction of astrocytosis. Patients with partial urea cycle enzyme deficiencies may have a much later presentation, usually with hepatogastric, neurologic, or psychiatric symptoms. Seizures in the neonate are a sign of acute hyperammonemia and occur in approximately 50% of severely hyperammonemic neonates. The electroencephalographic (EEG) abnormalities may parallel the clinical course with improvement in the background and resolution of the epileptiform discharges. Measurement of blood ammonia after a protein load may help to establish the diagnosis in patients with normal baseline ammonia levels. Hemodialysis and hemofiltration can be used to lower ammonia levels acutely while measures to reverse the catabolic state are implemented by infusion of glucose and insulin.