title: Normal Neurological Development During Infancy Despite Massive Hyperammonemia in Early Treated NAGS Deficiency.
abstract: A girl born at term was admitted to the neonatal intensive care unit because of mild respiratory distress after a complicated delivery. She recovered, but was readmitted at 58 h of life with mild respiratory distress and increased muscle tone. Neonatal abstinence syndrome because of maternal use of lithium, clomipramine, and quetiapine during pregnancy was suspected, but at 115 h of life she became unresponsive, and an immediate work-up for coma was initiated. An ammonia of 2,235 μmol/l was found, and treatment with sodium benzoate, sodium phenylacetate, arginine, glucose, and N-carbamylglutamate (NCG, Carbaglu®) was started. This treatment normalized plasma ammonia levels within 16 h.Biochemical results suggested a mitochondrial urea cycle defect, either of N-acetyl glutamate synthase (NAGS) or carbamoyl phosphate synthetase 1. DNA analysis later confirmed a diagnosis of NAGS deficiency. Under long-term treatment with NCG, the patient developed normally at last follow-up at 7 months of age.In conclusion, the standard neonatal situation of a neurologically compromised newborn turned out as a treatable rare inborn error of metabolism. In all neonates with somnolence and coma and hence the suspicion of a bacterial sepsis, plasma ammonia should be included in the work-up. NCG was immediately beneficial for the patient described and should be considered for the emergency treatment of neonatal hyperammonemia. Even a very high ammonia may allow for a normal neurological development in infancy (and possibly beyond).
authors.affiliation: Neonatal Intensive Care Unit, Children's Department, Haukeland University Hospital, 5021, Bergen, Norway. hallvard.reigstad@helse-bergen.no.
authors.forename: Hallvard
authors.initials: H
authors.lastname: Reigstad
authors.affiliation: Department of Medical Biochemistry, Oslo University Hospital, 0424, Oslo, Norway.
authors.forename: Berit
authors.initials: B
authors.lastname: Woldseth
authors.affiliation: Division of Metabolism and Children's Research Center, University Children's Hospital Zurich, Eleonore Foundation, Steinwiesstrasse 75, 8032, Zürich, Switzerland.
authors.forename: Johannes
authors.initials: J
authors.lastname: Häberle
keywords: Case report; Hyperammonemia; N-acetyl glutamate synthase deficiency; Neonatal coma