Brain Biomarkers of Long-Term Outcome of Neonatal Onset Urea Cycle Disorder
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 nit...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2016-11-01
|
| Series: | International Journal of Neonatal Screening |
| Subjects: | |
| Online Access: | http://www.mdpi.com/2409-515X/2/4/10 |
| _version_ | 1819010711496425472 |
|---|---|
| author | Maha Mourad Johannes Häberle Matthew T. Whitehead Tamar Stricker Andrea L. Gropman |
| author_facet | Maha Mourad Johannes Häberle Matthew T. Whitehead Tamar Stricker Andrea L. Gropman |
| author_sort | Maha Mourad |
| collection | DOAJ |
| description | 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 effects include deficits in working memory and executive function. To date, there are no predictors of prognosis of infants with neonatal onset OTCD outside of the plasma ammonia level at presentation and duration of a 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 of life with plasma ammonia and glutamine of 677 and 4024 micromol/L respectively, and was found to have a missense mutation in Exon 4 (p. R129H). Treatment included protein restriction, sodium benzoate, and citrulline, arginine, and iron. Despite compliance, he suffered recurrent acute hyperammonemic episodes triggered by infections or catabolic stressors. We discuss the long-term effects of the hyperammonemic episodes by following MRI-based disease biomarkers. |
| first_indexed | 2024-12-21T01:16:36Z |
| format | Article |
| id | doaj.art-8d13b9c8e1cf4191bb0c19b7e77ec804 |
| institution | Directory Open Access Journal |
| issn | 2409-515X |
| language | English |
| last_indexed | 2024-12-21T01:16:36Z |
| publishDate | 2016-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Neonatal Screening |
| spelling | doaj.art-8d13b9c8e1cf4191bb0c19b7e77ec8042022-12-21T19:20:46ZengMDPI AGInternational Journal of Neonatal Screening2409-515X2016-11-01241010.3390/ijns2040010ijns2040010Brain Biomarkers of Long-Term Outcome of Neonatal Onset Urea Cycle DisorderMaha Mourad0Johannes Häberle1Matthew T. Whitehead2Tamar Stricker3Andrea L. Gropman4Touro College of Osteopathic Medicine, Middletown, NY 10940, USAUniversity Children’s Hospital and Children’s Research Center, Zurich 8091, SwitzerlandDepartment of Neurology, Children’s National Health System, 111 Michigan Avenue, N.W., Washington, DC 20010, USAUniversity Children’s Hospital and Children’s Research Center, Zurich 8091, SwitzerlandDepartment of Neurology, Children’s National Health System, 111 Michigan Avenue, N.W., Washington, DC 20010, USAUrea 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 effects include deficits in working memory and executive function. To date, there are no predictors of prognosis of infants with neonatal onset OTCD outside of the plasma ammonia level at presentation and duration of a 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 of life with plasma ammonia and glutamine of 677 and 4024 micromol/L respectively, and was found to have a missense mutation in Exon 4 (p. R129H). Treatment included protein restriction, sodium benzoate, and citrulline, arginine, and iron. Despite compliance, he suffered recurrent acute hyperammonemic episodes triggered by infections or catabolic stressors. We discuss the long-term effects of the hyperammonemic episodes by following MRI-based disease biomarkers.http://www.mdpi.com/2409-515X/2/4/10urea cycle disorderornithine transcarbamylase deficiencymagnetic resonance imagingmagnetic resonance spectroscopy |
| spellingShingle | Maha Mourad Johannes Häberle Matthew T. Whitehead Tamar Stricker Andrea L. Gropman Brain Biomarkers of Long-Term Outcome of Neonatal Onset Urea Cycle Disorder International Journal of Neonatal Screening urea cycle disorder ornithine transcarbamylase deficiency magnetic resonance imaging magnetic resonance spectroscopy |
| title | Brain Biomarkers of Long-Term Outcome of Neonatal Onset Urea Cycle Disorder |
| title_full | Brain Biomarkers of Long-Term Outcome of Neonatal Onset Urea Cycle Disorder |
| title_fullStr | Brain Biomarkers of Long-Term Outcome of Neonatal Onset Urea Cycle Disorder |
| title_full_unstemmed | Brain Biomarkers of Long-Term Outcome of Neonatal Onset Urea Cycle Disorder |
| title_short | Brain Biomarkers of Long-Term Outcome of Neonatal Onset Urea Cycle Disorder |
| title_sort | brain biomarkers of long term outcome of neonatal onset urea cycle disorder |
| topic | urea cycle disorder ornithine transcarbamylase deficiency magnetic resonance imaging magnetic resonance spectroscopy |
| url | http://www.mdpi.com/2409-515X/2/4/10 |
| work_keys_str_mv | AT mahamourad brainbiomarkersoflongtermoutcomeofneonatalonsetureacycledisorder AT johanneshaberle brainbiomarkersoflongtermoutcomeofneonatalonsetureacycledisorder AT matthewtwhitehead brainbiomarkersoflongtermoutcomeofneonatalonsetureacycledisorder AT tamarstricker brainbiomarkersoflongtermoutcomeofneonatalonsetureacycledisorder AT andrealgropman brainbiomarkersoflongtermoutcomeofneonatalonsetureacycledisorder |