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).
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Acknowledgements
The mutation analysis of the patient and parents was supported by Orphan Europe Recordati. This had however no influence on the design and writing of this manuscript. Work on urea cycle disorders is supported by the Swiss National Science Foundation (grant 310030_153196 to Johannes Häberle).
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Communicated by: Bridget Wilcken
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Hallvard Reigstad and Berit Woldseth declare no conflict of interest. Johannes Häberle has received travel support and honoraria as an invited speaker from Orphan Europe Recordati.
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Informed consent was obtained from the parents of the patient.
This chapter does not contain any studies with human or animal subjects performed by any of the authors.
Hallvard Reigstad has been responsible for the treatment and follow-up of the patient, and is the main author of this chapter.
Berit Woldseth has been responsible for the biochemical analyses and has revised the chapter.
Johannes Häberle has been responsible for the genetic analyses and has revised the chapter.
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Reigstad, H., Woldseth, B., Häberle, J. (2017). Normal Neurological Development During Infancy Despite Massive Hyperammonemia in Early Treated NAGS Deficiency. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 37. JIMD Reports, vol 37. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2017_13
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DOI: https://doi.org/10.1007/8904_2017_13
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