title: Tract-based evaluation of white matter damage in individuals with early-treated phenylketonuria.
abstract: Previous research has documented white matter abnormalities in the brains of individuals with early-treated phenylketonuria (ETPKU). The majority of these past studies have relied on a region-based approach which focused on a limited number of spatially-defined regions within the brain. In the present study, we used diffusion tensor imaging (DTI) in conjunction with tract-based spatial statistics (TBSS) to perform an extensive examination of white matter tracts in the brains of ten individuals with ETPKU (mean age = 23.2 years) and 12 healthy non-PKU individuals (mean age = 23.5 years). Consistent with past research, we found that mean diffusivity (MD) was significantly restricted in the ETPKU group, and fractional anisotropy (FA) was comparable between the ETPKU and non-PKU groups. Moreover, we found restricted axial diffusivity (AD) and radial diffusivity (RD) in our ETPKU in numerous white matter tracts, suggesting widespread white matter compromise in ETPKU. In addition, this white matter pathology was more evident in older ETPKU participants with higher blood phenylalanine (phe) levels as compared to younger participants with lower phe levels.
authors.affiliation: Department of Psychological Sciences, University of Missouri, 210 McAlester Hall, Columbia, MO, 65203, USA.
authors.forename: Huiling
authors.initials: H
authors.lastname: Peng
authors.forename: Dawn
authors.initials: D
authors.lastname: Peck
authors.forename: Desirée A
authors.initials: DA
authors.lastname: White
authors.forename: Shawn E
authors.initials: SE
authors.lastname: Christ
mesh_terms: D000293:Adolescent; D000328:Adult; D016880:Anisotropy; D016022:Case-Control Studies; D002648:Child; D056324:Diffusion Tensor Imaging / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D010649:Phenylalanine / Q000097:blood; D010661:Phenylketonurias / Q000097:blood / Q000473:pathology*; D066127:White Matter / Q000473:pathology*; D055815:Young Adult
chemical_list: D010649:Phenylalanine
references.citation: Brain. 1993 Aug;116 ( Pt 4):811-21
references.pmid: 8353710
references.citation: Nat Protoc. 2007;2(3):499-503
references.pmid: 17406613
references.citation: AJNR Am J Neuroradiol. 2006 Apr;27(4):879-81
references.pmid: 16611782
references.citation: AJNR Am J Neuroradiol. 2004 Oct;25(9):1569-74
references.pmid: 15502140
references.citation: J Inherit Metab Dis. 1997 Jul;20(3):367-9
references.pmid: 9266357
references.citation: Lancet. 1994 Jul 9;344(8915):87-90
references.pmid: 7912392
references.citation: Radiol Med. 2009 Apr;114(3):461-74
references.pmid: 19277839
references.citation: J Inherit Metab Dis. 2007 Apr;30(2):209-16
references.pmid: 17245558
references.citation: Mol Genet Metab. 2010;99 Suppl 1:S18-21
references.pmid: 20123465
references.citation: Acta Radiol. 2001 Sep;42(5):459-66
references.pmid: 11552882
references.citation: Mol Genet Metab. 2010;99 Suppl 1:S1-2
references.pmid: 20123461
references.citation: AJNR Am J Neuroradiol. 2001 Sep;22(8):1583-6
references.pmid: 11559511
references.citation: N Engl J Med. 1986 Mar 6;314(10):593-8
references.pmid: 3945244
references.citation: Brain. 2000 Aug;123 ( Pt 8):1667-76
references.pmid: 10908196
references.citation: Br Med J. 1978 Sep 9;2(6139):723-6
references.pmid: 698696
references.citation: Pediatrics. 1957 Aug;20(2):290-302
references.pmid: 13452670
references.citation: Eur J Pediatr. 1993 Dec;152(12):1012-20
references.pmid: 8131802
references.citation: J Inherit Metab Dis. 1986;9 Suppl 2:169-77
references.pmid: 2877115
references.citation: Magn Reson Med. 2007 Dec;58(6):1145-56
references.pmid: 18046700
references.citation: Radiology. 2005 Aug;236(2):630-6
references.pmid: 16040919
references.citation: Radiology. 2004 Jan;230(1):77-87
references.pmid: 14645885
references.citation: Cell Mol Neurobiol. 2011 Jul;31(5):653-62
references.pmid: 21516352
references.citation: Mol Genet Metab. 2010;99 Suppl 1:S22-32
references.pmid: 20123466
references.citation: Mol Genet Metab. 2010;99 Suppl 1:S41-6
references.pmid: 20123469
references.citation: J Magn Reson Imaging. 2008 May;27(5):998-1004
references.pmid: 18425822
references.citation: Neuroimage. 2006 Jul 15;31(4):1487-505
references.pmid: 16624579
references.citation: Mol Genet Metab. 2010;99 Suppl 1:S3-9
references.pmid: 20123467
references.citation: Dev Med Child Neurol. 2004 Apr;46(4):230-8
references.pmid: 15077700
references.citation: J Magn Reson B. 1994 Mar;103(3):247-54
references.pmid: 8019776
references.citation: Hum Brain Mapp. 2002 Jan;15(1):1-25
references.pmid: 11747097
references.citation: J Pediatr. 1995 Aug;127(2):251-5
references.pmid: 7636650
references.citation: Lancet. 1990 Sep 8;336(8715):602-5
references.pmid: 1975386
references.citation: Biochim Biophys Acta. 1978 Feb 16;517(2):473-85
references.pmid: 245312