White matter integrity and executive abilities following treatment with tetrahydrobiopterin (BH4) in individuals with phenylketonuria.
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.
Department of Psychology, Campus Box 1125, Washington University, St. Louis, MO 63130, USA. Electronic address: dawhite@wustl.edu.
Desirée A
DA
White
Jo Ann V
JA
Antenor-Dorsey
Dorothy K
DK
Grange
Tamara
T
Hershey
Jerrel
J
Rutlin
Joshua S
JS
Shimony
Robert C
RC
McKinstry
Shawn E
SE
Christ
D000293:Adolescent; D000328:Adult; D001708:Biopterins / Q000031:analogs & derivatives / Q000627:therapeutic use; D001921:Brain / Q000473:pathology* / Q000503:physiopathology*; D016022:Case-Control Studies; D002648:Child; D056324:Diffusion Tensor Imaging; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D010649:Phenylalanine / Q000097:blood; D010661:Phenylketonurias / Q000097:blood / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D016896:Treatment Outcome; D055815:Young Adult
D001708:Biopterins; D010649:Phenylalanine; C003402:sapropterin
Diffusion tensor imaging; Executive; Phenylketonuria; Sapropterin; Tetrahydrobiopterin; White matter