Date of Award
Campus Access Dissertation
Phenylketonuria (PKU) is a metabolic disorder that results in white matter abnormalities with varying degrees of severity. The analysis of brain structure in children with PKU using magnetic resonance imaging (MRI) has been limited by the reliance on qualitative data to characterize white matter abnormalities. In addition, the few brain MRI studies that have used a quantitative approach have treated a wide age range of pediatric and adult cases as a homogeneous group, which fails to address potential developmental differences within the disorder. The current study characterized normal-appearing white matter in a pediatric PKU sample (n = 36) through comparison to a normative sample and a neurologically-normal control sample (n=69). At adolescence, the PKU group showed signs of increased white matter volumes compared to the normative data and control group, which coincided with increased disease severity. At younger ages, no differences between white matter volumes were present. Individuals with PKU also demonstrated decreased total corpus callosum area when compared to the control group, particularly in the posterior midbody area. Although the findings of increased global white matter volumes and decreased corpus callosum areas in PKU are contradictory, they both point to overall white matter abnormalities in a pediatric PKU sample. Furthermore the direction of the discrepancies may be related to differential developmental processes: increased volumes in the global white matter volumes were related to an emerging developmental deficit and decreased corpus callosum area was associated with a continuous developmental deficit. These findings provide evidence that children who have been treated early and continuously for PKU are at risk for neurological disturbance in late adolescence, when Phe-restricted diets are likely to be relaxed.
Sanchez, C. E.(2012). Quantitative Analysis of Normal-Appearing White Matter In Pediatric Phenylketonuria. (Doctoral dissertation). Retrieved from https://scholarcommons.sc.edu/etd/2153