School of Medicine and Health Sciences Poster Presentations
Defining Brain Chemical Changes and Areas of the Brain Most Affected by High Ammonia Levels in Children with Urea Cycle Disorder
Poster Number
273
Document Type
Poster
Publication Date
3-2016
Abstract
Background: Urea cycle disorders are amongst the most common of the inborn errors of metabolism. These disorders affect up to 1/25,000 live births in the United States and the number of children affected by partial defects may be much higher . Urea cycle disorders can lead to high rates of disability if not treated early. The urea cycle converts nitrogenous waste, a toxic byproduct of protein metabolism, into urea, a safe compound, which is excreted in the urine. Children with urea cycle disorders are unable to fully metabolize nitrogenous waste in the liver, resulting in high levels of ammonia in the blood. Hyperammonemia has well known neurologic sequelae. However, the structural and chemical consequences of high ammonia in the brain of a developing child have not been well defined. Furthermore, due to compartmentalization, ammonia levels in the blood do not correlate well with levels of ammonia in the brain. Additionally, patients that experience high brain ammonia levels are not always symptomatic.
Objective: To define with magnetic resonance spectroscopy (MRS) how the chemical levels of N-acetylaspartic acid, glutamine, glutamate, creatine, choline, myoinositol, lactate, and lipids vary from the norm in a child experiencing hyperammonemia. An additional objective is to evaluate the brain magnetic resonance images (MRI) of these same patients to identify parts of the brain most affected by high ammonia levels.
Methods: This was a retrospective study in which 8 patients with various genetic defects in the urea cycle were identified. A neuro-radiologist read the MRI and MRS data and the data were analyzed for similarities.
Results: MRS data showed that brain levels of myoinositol are decreased in patients with hyperammonemia. Levels of lactate, glutamate, glutamine, and choline are increased. N-acetylaspartic acid may be either decreased or normal. Creatine and lipid levels remain normal. MRI data showed that areas of the brain affected by high ammonia are the peri-insular region, the globus pallidus, and the frontal, temporal, and parietal lobes. The thalamus, occipital lobe, corpus callosum, and brainstem were unaffected in these patients.
Conclusion: The findings in this small retrospective study indicate that there may be a distinct chemical footprint of changes that occur in the brain when ammonia levels are high. This suggests that MRS could be a better tool to evaluate the biochemical consequences of high levels of ammonia in the brain rather than a blood ammonia level. Furthermore, MRI data suggest that there are distinct regions of the brain that are more sensitive to the effects of hyperammonemia than others.
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Open Access
1
Defining Brain Chemical Changes and Areas of the Brain Most Affected by High Ammonia Levels in Children with Urea Cycle Disorder
Background: Urea cycle disorders are amongst the most common of the inborn errors of metabolism. These disorders affect up to 1/25,000 live births in the United States and the number of children affected by partial defects may be much higher . Urea cycle disorders can lead to high rates of disability if not treated early. The urea cycle converts nitrogenous waste, a toxic byproduct of protein metabolism, into urea, a safe compound, which is excreted in the urine. Children with urea cycle disorders are unable to fully metabolize nitrogenous waste in the liver, resulting in high levels of ammonia in the blood. Hyperammonemia has well known neurologic sequelae. However, the structural and chemical consequences of high ammonia in the brain of a developing child have not been well defined. Furthermore, due to compartmentalization, ammonia levels in the blood do not correlate well with levels of ammonia in the brain. Additionally, patients that experience high brain ammonia levels are not always symptomatic.
Objective: To define with magnetic resonance spectroscopy (MRS) how the chemical levels of N-acetylaspartic acid, glutamine, glutamate, creatine, choline, myoinositol, lactate, and lipids vary from the norm in a child experiencing hyperammonemia. An additional objective is to evaluate the brain magnetic resonance images (MRI) of these same patients to identify parts of the brain most affected by high ammonia levels.
Methods: This was a retrospective study in which 8 patients with various genetic defects in the urea cycle were identified. A neuro-radiologist read the MRI and MRS data and the data were analyzed for similarities.
Results: MRS data showed that brain levels of myoinositol are decreased in patients with hyperammonemia. Levels of lactate, glutamate, glutamine, and choline are increased. N-acetylaspartic acid may be either decreased or normal. Creatine and lipid levels remain normal. MRI data showed that areas of the brain affected by high ammonia are the peri-insular region, the globus pallidus, and the frontal, temporal, and parietal lobes. The thalamus, occipital lobe, corpus callosum, and brainstem were unaffected in these patients.
Conclusion: The findings in this small retrospective study indicate that there may be a distinct chemical footprint of changes that occur in the brain when ammonia levels are high. This suggests that MRS could be a better tool to evaluate the biochemical consequences of high levels of ammonia in the brain rather than a blood ammonia level. Furthermore, MRI data suggest that there are distinct regions of the brain that are more sensitive to the effects of hyperammonemia than others.
Comments
Presented at: GW Research Days 2016