White Matter Integrity and Executive Abilities Following Treatment with Tetrahydrobiopterin (BH4) in Individuals with Phenylketonuria

Overview

Journal Mol Genet Metab

Specialty Endocrinology

Date 2013 Aug 10

PMID 23928118

Citations 15

Authors

Desiree A White

Jo Ann V Antenor-Dorsey

Dorothy K Grange

Tamara Hershey

Jerrel Rutlin

Joshua S Shimony

Robert C McKinstry

Shawn E Christ

Affiliations

Soon will be listed here.

Abstract

Tetrahydrobiopterin (BH(4)) lowers blood phenylalanine (Phe) in individuals with PKU who are responders, but its effects on the brain and cognition have not been explored thoroughly. We examined blood Phe, microstructural white matter integrity, and executive abilities in 12 BH(4) responders before (i.e., baseline) and after (i.e., follow-up) six months of treatment with BH(4). Compared with baseline, Phe in these responders decreased by 51% during a 4 week screening period after initiation of treatment and remained lowered by 37% over the 6 month follow-up period. Significant improvements in white matter integrity, evaluated by mean diffusivity from diffusion tensor imaging, were also found following six months of treatment. Improvements in executive abilities were not identified, although six months may have been a period too brief for changes in cognition to follow changes in the brain. To our knowledge, our study is the first to explore relationships among Phe, white matter integrity, executive abilities, and BH(4) treatment within a single study.

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