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Mol Genet Metab Rep. 2017 Feb 23;12:8-13. doi: 10.1016/j.ymgmr.2017.01.013. eCollection 2017 Sep.

Pretreatment cognitive and neural differences between sapropterin dihydrochloride responders and non-responders with phenylketonuria.

Author information

1
Department of Psychological and Brain Sciences, Campus Box 1125, Washington University, St. Louis, MO 63130, USA.
2
Mallinckrodt Institute of Radiology, Campus Box 8131, Washington University School of Medicine, St. Louis, MO 63110, USA.
3
Department of Pediatrics, Campus Box 8116, Washington University School of Medicine, St. Louis, MO 63110, USA.
4
Department of Psychological Sciences, 210 McAlester Hall, University of Missouri, Columbia, MO 65211, USA.
5
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.

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 BH4 responders and non-responders, cognitive and neural differences remain largely unexplored. To this end, we compared intelligence and white matter integrity prior to treatment with BH4 in 13 subsequent BH4 responders with PKU, 16 subsequent BH4 non-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.

KEYWORDS:

BH4; Diffusion tensor imaging; IQ; Intelligence; Phenylketonuria; Sapropterin dihydrochloride; White matter

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