JIMD Reports, Volume 27

Julie Chantreuil, Géraldine Favrais, Nadine Fakhri, Marine Tardieu, Nicolas Roullet-Renoleau, Thierry Perez, Nadine Travers, Laurent Barantin, Baptiste Morel, Elie Saliba, François Labarthe

Ornithine transcarbamylase deficiency (OTCD) is an inborn error of urea cycle resulting in increased plasma levels of ammonia and glutamine and cerebral edema. However, the underlying mechanism of brain cytotoxicity remains controversial. Our objective is to present an unusual acute hyperammonemic crisis suggesting a key role of brain glutamine to mediate ammonia neurotoxicity and the interest of intracerebral pressure (ICP) monitoring to maintain adequate cerebral perfusion pressure and to prevent neurological damages. A 6-year-old boy with OTCD was admitted for an acute hyperammonemic encephalopathy following viral infection. At admission, he presented vomiting, confusion, lethargy (Glasgow scale 7/15), and bilateral papilledema, suggesting cerebral edema. Plasma ammonia level was slightly increased (194 μmol/L, rr 25-50 μmol/L), contrasting with the severity of neurological deterioration and with high levels of glutamine in plasma (1,949 μmol/L, rr 335-666 μmol/L) and the brain (10-fold increase on in vivo MR spectroscopy). The patient was placed on neuroprotective treatments and respiratory support. With a hypercaloric protein-free diet and nitrogen scavenger drugs, plasma levels of ammonia and glutamine rapidly decreased without neurological improvement. Continuous ICP monitoring showed repetitive peaks of pressure up to 60 mmHg in the first four days and was helpful to manage neuroprotective treatments. After several days, the patient progressively recovered without cognitive or motor disability. This case report highlights the discrepancy between the severity of neurological impairment, presumably related to high level of brain glutamine, and plasma levels of ammonia or glutamine in a child with acute hyperammonemic encephalopathy related to OTCD. In this situation, continuous ICP monitoring was helpful to manage neuroprotective treatments and prevent brain damages.