TY - JOUR
T1 - Prolonged exposure to high and variable phenylalanine levels over the lifetime predicts brain white matter integrity in children with phenylketonuria
AU - Hood, Anna
AU - Antenor-Dorsey, Jo Ann V.
AU - Rutlin, Jerrel
AU - Hershey, Tamara
AU - Shimony, Joshua S.
AU - McKinstry, Robert C.
AU - Grange, Dorothy K.
AU - Christ, Shawn E.
AU - Steiner, Robert
AU - White, Desiree A.
N1 - Publisher Copyright:
© 2014 Elsevier Inc.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - In this study, we retrospectively examined the microstructural white matter integrity of children with early- and continuously-treated PKU (. N=. 36) in relation to multiple indices of phenylalanine (Phe) control over the lifetime. White matter integrity was assessed using mean diffusivity (MD) from diffusion tensor imaging (DTI). Eight lifetime indices of Phe control were computed to reflect average Phe (mean, index of dietary control), variability in Phe (standard deviation, standard error of estimate, % spikes), change in Phe with age (slope), and prolonged exposure to Phe (mean exposure, standard deviation exposure). Of these indices, mean Phe, mean exposure, and standard deviation exposure were the most powerful predictors of widespread microstructural white matter integrity compromise. Findings from the two previously unexamined exposure indices reflected the accumulative effects of elevations and variability in Phe. Given that prolonged exposure to elevated and variable Phe was particularly detrimental to white matter integrity, Phe should be carefully monitored and controlled throughout childhood, without liberalization of Phe control as children with PKU age.
AB - In this study, we retrospectively examined the microstructural white matter integrity of children with early- and continuously-treated PKU (. N=. 36) in relation to multiple indices of phenylalanine (Phe) control over the lifetime. White matter integrity was assessed using mean diffusivity (MD) from diffusion tensor imaging (DTI). Eight lifetime indices of Phe control were computed to reflect average Phe (mean, index of dietary control), variability in Phe (standard deviation, standard error of estimate, % spikes), change in Phe with age (slope), and prolonged exposure to Phe (mean exposure, standard deviation exposure). Of these indices, mean Phe, mean exposure, and standard deviation exposure were the most powerful predictors of widespread microstructural white matter integrity compromise. Findings from the two previously unexamined exposure indices reflected the accumulative effects of elevations and variability in Phe. Given that prolonged exposure to elevated and variable Phe was particularly detrimental to white matter integrity, Phe should be carefully monitored and controlled throughout childhood, without liberalization of Phe control as children with PKU age.
KW - Brain
KW - Diffusion tensor imaging
KW - Exposure
KW - Phenylalanine
KW - Phenylketonuria
KW - White matter
UR - http://www.scopus.com/inward/record.url?scp=84920441309&partnerID=8YFLogxK
U2 - 10.1016/j.ymgme.2014.11.007
DO - 10.1016/j.ymgme.2014.11.007
M3 - Article
C2 - 25481106
AN - SCOPUS:84920441309
SN - 1096-7192
VL - 114
SP - 19
EP - 24
JO - Molecular genetics and metabolism
JF - Molecular genetics and metabolism
IS - 1
ER -