Date of Award


Document Type


Degree Name

Master of Science (MS)


Biological Sciences

Committee Chair

Gordon MacGregor

Committee Member

Roy Magnuson

Committee Member

Joseph Ng


Tyrosinosis, Cognition disorders, Myelination, Inborn errors of metabolism


The exact mechanism behind the recent reports of impaired neurocognitive function in individuals with the rare genetic disorder Hereditary Tyrosinemia Type I (HT1) has yet to be determined. This disorder stems from lack of expression of the gene fumarylacetoacetate hydrolase (FAH), which is responsible for tyrosine catabolism. This subsequently leads to a buildup of tyrosine and associated harmful metabolites that will cause sever liver dysfunction and cancer if treatment is not provided. The drug 2-[2-nitro-4-(trifluoromethylbenzoyl) cyclohexane-1,3-dione (NTBC) has proven to be effective in stopping the negative consequences on the liver and kidneys by inhibiting an enzyme upstream in the metabolic pathway. Although this treatment has allowed for prolonged survival in HT1 individuals, it remains unknown if NTBC has any negative effects on brain function. Studies on mice have illustrated that the disease process causes altered social behavior and cognition, mimicking the effects observed in patients with the disorder. Additionally, mice with HT1 displayed changes in myelination of the cerebral cortex. These results suggest that the neuropsychological problems observed in individuals with HT1 stem from the disease process, and that the glial cells responsible for myelination could provide a source for the increased myelination and abnormal social behavior observed in mice with HT1.



To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.