title: Pretreatment cognitive and neural differences between sapropterin dihydrochloride responders and non-responders with phenylketonuria.
abstract: Sapropterin dihydrochloride (BH4) reduces phenylalanine (Phe) levels and improves white matter integrity in a subset of individuals with phenylketonuria (PKU) known as "responders." Although prior research has identified biochemical and genotypic differences between BH4responders and non-responders, cognitive and neural differences remain largely unexplored. To this end, we compared intelligence and white matter integrity prior to treatment with BH4in 13 subsequent BH4responders with PKU, 16 subsequent BH4non-responders with PKU, and 12 healthy controls. Results indicated poorer intelligence and white matter integrity in non-responders compared to responders prior to treatment. In addition, poorer white matter integrity was associated with greater variability in Phe across the lifetime in non-responders but not in responders. These results underscore the importance of considering PKU as a multi-faceted, multi-dimensional disorder and point to the need for additional research to delineate characteristics that predict response to treatment with BH4.
authors.affiliation: Department of Psychological and Brain Sciences, Campus Box 1125, Washington University, St. Louis, MO 63130, USA.
authors.forename: Zoë
authors.initials: Z
authors.lastname: Hawks
authors.affiliation: Mallinckrodt Institute of Radiology, Campus Box 8131, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Shimony
authors.affiliation: Mallinckrodt Institute of Radiology, Campus Box 8131, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Jerrel
authors.initials: J
authors.lastname: Rutlin
authors.affiliation: Department of Pediatrics, Campus Box 8116, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Dorothy K
authors.initials: DK
authors.lastname: Grange
authors.affiliation: Department of Psychological Sciences, 210 McAlester Hall, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Shawn E
authors.initials: SE
authors.lastname: Christ
authors.affiliation: Department of Psychological and Brain Sciences, Campus Box 1125, Washington University, St. Louis, MO 63130, USA; Department of Pediatrics, Campus Box 8116, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Desirée A
authors.initials: DA
authors.lastname: White
keywords: BH4; Diffusion tensor imaging; IQ; Intelligence; Phenylketonuria; Sapropterin dihydrochloride; White matter