Preprint Case Report Version 1 NOT YET PEER-REVIEWED

Brain Biomarkers of Long-term Outcome of Neonatal Onset Urea Cycle Disorder

  1. Touro College of Osteopathic Medicine, Middletown, NY 10027, USA
  2. University Children’s Hospital and Children’s Research Center, Zurich 8032, Switzerland
  3. Children’s National Health System, Washington, DC 20010, USA
  4. Georgetown University Hospital, Washington, DC 20007, USA
Version 1 : Received: 7 August 2016 / Approved: 9 August 2016 / Online: 9 August 2016 (12:03:57 CEST)

A peer-reviewed article of this Preprint also exists.

Mourad, M.; Häberle, J.; Whitehead, M.; Stricker, T.; Gropman, A.L. Brain Biomarkers of Long-Term Outcome of Neonatal Onset Urea Cycle Disorder. Int. J. Neonatal Screen. 2016, 2, 10. Mourad, M.; Häberle, J.; Whitehead, M.; Stricker, T.; Gropman, A.L. Brain Biomarkers of Long-Term Outcome of Neonatal Onset Urea Cycle Disorder. Int. J. Neonatal Screen. 2016, 2, 10.

Journal reference: Int. J. Neonatal Screen. 2016, 2, 10
DOI: 10.3390/ijns2040010

Abstract

Urea cycle disorders (UCDs) are common inborn errors of metabolism, with an incidence of one in 30,000 births. They are caused by deficiencies in any of six enzymes and two carrier proteins, the most common being Ornithine Transcarbamylase Deficiency (OTCD). OTCD results in impairment to excrete nitrogen, causing toxic buildup of ammonia with resultant encephalopathy. Hyperammonemia (HA) induces the conversion of glutamate to glutamine in the brain. Excess glutamine in the brain causes osmotic changes cerebral edema, changes in astrocyte morphology, and cell death. Acute symptoms of HA include vomiting, hyperventilation, seizures, and irritability. Long-term neurological changes include deficits in working memory and executive function. To date, there are no predictors of prognosis of infants with neonatal onset OTCD outside of plasma ammonia level at presentation and duration of hyperammonemic coma. We provide a comprehensive analysis of a 16-year-old male with neonatal onset of OTCD as an example of how brain biomarkers may be useful to monitor disease course and outcome. This male presented at 8 days post natal with plasma ammonia and glutamine of 677 and 4024 micromol/L and had a missense mutation in Exon 4 (p.R129H). Treatment included protein restriction, sodium benzoate, and citrulline, arginine, and iron. He suffered recurrent acute hyperammonemic episodes despite compliance, triggered by infections or catabolic stressors. We discuss the long-term effects of the hyperammonemic episodes by following MRI based disease biomarkers.

Subject Areas

urea cycle disorder; ornithine transcarbamylase deficiency; magnetic resonance imaging; magnetic resonance spectroscopy

Readers' Comments and Ratings (0)

Discuss and rate this article
Views 129
Downloads 126
Comments 0
Metrics 0
Discuss and rate this article

×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.