Systemic Biomarkers of Brain Injury From Hyperammonemia
Ammonia is a waste product of protein and amino acid catabolism and is also a potent neurotoxin. High blood ammonia levels on the brain can manifest as cytotoxic brain edema and vascular compromise leading to intellectual and developmental disabilities. The following aims are proposed: Aim 1 of this study will be to determine the chronology of biomarkers of brain injury in response to a hyperammonemic (HA) brain insult in patients with an inherited hyperammonemic disorder. Aim 2 will be to determine if S100B, NSE, and UCHL1 are altered in patients with two other inborn errors of metabolism, Maple Syrup Urine Disease (MSUD) and Glutaric Acidemia (GA1).
• Inherited Hyperammonemias:
• A clinical diagnosis of 1 of 7 diagnosed urea cycle disorders:
• N-acetylglutamate Synthetase Deficiency (NAGS)
• Carbamyl Phosphate Synthetase Deficiency (CPSD)
• Ornithine Transcarbamylase Deficiency (OTCD)
• Argininosuccinate Synthetase Deficiency (ASD)
• Argininosuccinate Lyase Deficiency (ALD)
• Arginase Deficiency (AD)
• Hyperammonemia-Hyperornithinemia-Homocitrullinuria (HHH)
• A clinical diagnosis of 1 of 2 organic acidemias:
• Propionic Acidemia (PA)
• Methylmalonic Acidemia (MMA)
• Acute metabolic disorder without hyperammonemia, with neurological sequelae
• Maple Syrup Urine Disease (MSUD)
• Glutaric Acidemia (GA1)
• Acute metabolic disorder without hyperammonemia and without neurological sequelae
• Fatty Acid Oxidation Disorders:
• Medium Chain-Acyl CoA Dehydrogenase Deficiency
• Very Long Chain-Acyl CoA Dehydrogenase Deficiency
• Trifunctional Protein Deficiency
• Long Chain Hydroxyacyl-CoA Dehydrogenase Deficiency
• Carnitine Palmitoyltransferase I or II Deficiency
• Carnitine/Acylcarnitine Translocase Deficiency
• Primary Carnitine Transport Deficiency
• Hypoxic-Ischemic Encephalopathy