OBJECTIVE: To gain insights into the nature and pathogenesis of white matter (WM) abnormalities in PKU. METHODS: Thirty-two patients with phenylalanine hydroxylase deficiency (21 with early and 11 with late diagnosis and treatment) and 30 healthy controls underwent an integrated clinical, neuroimaging (3.0 T MRI, diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI)) and neurochemical (1H MRS) investigation. RESULTS: All patients had white matter abnormalities on T2-weighted (T2W) and fluid-attenuated inversion recovery (FLAIR) scans; parietal white was consistently affected, followed by occipital, frontal and temporal white matter. T1-weighted hypointense alterations were also found in 8 of 32 patients. DWI hyperintense areas overlapped with those detected on T2W/FLAIR. The apparent diffusion coefficient (ADC) was reduced and correlated inversely with severity of white matter involvement. Fractional anisotropy index, eigenvalues lambda(min), lambda(middle), lambda(max) obtained from DTI data, and the principal brain metabolites assessed by 1H MRS (except brain phenylalanine (Phe)) were normal. Brain Phe peak was detected in all but two subjects. Brain and blood Phe were strictly associated. Blood Phe at the diagnosis, patient's age, and concurrent brain Phe independently influence white matter alteration (as expressed by conventional MRI or ADC values). CONCLUSIONS: (a) MRI abnormalities in phenylketonuria are the result of a distinctive alteration of white matter suggesting the intracellular accumulation of a hydrophilic metabolite, which leaves unaffected white matter architecture and structure. (b) White matter abnormalities do not seem to reflect the mechanisms involved in the derangement of mental development in PKU. (c) Our data do not support the usefulness of conventional brain MRI examination in the clinical monitoring of phenylketonuria patients.
OBJECTIVE: To gain insights into the nature and pathogenesis of white matter (WM) abnormalities in PKU. METHODS: Thirty-two patients with phenylalanine hydroxylase deficiency (21 with early and 11 with late diagnosis and treatment) and 30 healthy controls underwent an integrated clinical, neuroimaging (3.0 T MRI, diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI)) and neurochemical (1H MRS) investigation. RESULTS: All patients had white matter abnormalities on T2-weighted (T2W) and fluid-attenuated inversion recovery (FLAIR) scans; parietal white was consistently affected, followed by occipital, frontal and temporal white matter. T1-weighted hypointense alterations were also found in 8 of 32 patients. DWI hyperintense areas overlapped with those detected on T2W/FLAIR. The apparent diffusion coefficient (ADC) was reduced and correlated inversely with severity of white matter involvement. Fractional anisotropy index, eigenvalues lambda(min), lambda(middle), lambda(max) obtained from DTI data, and the principal brain metabolites assessed by 1H MRS (except brain phenylalanine (Phe)) were normal. Brain Phe peak was detected in all but two subjects. Brain and blood Phe were strictly associated. Blood Phe at the diagnosis, patient's age, and concurrent brain Phe independently influence white matter alteration (as expressed by conventional MRI or ADC values). CONCLUSIONS: (a) MRI abnormalities in phenylketonuria are the result of a distinctive alteration of white matter suggesting the intracellular accumulation of a hydrophilic metabolite, which leaves unaffected white matter architecture and structure. (b) White matter abnormalities do not seem to reflect the mechanisms involved in the derangement of mental development in PKU. (c) Our data do not support the usefulness of conventional brain MRI examination in the clinical monitoring of phenylketonuria patients.
Authors: H C Lou; P B Toft; J Andresen; I Mikkelsen; B Olsen; F Güttler; S Wieslander; O Henriksen Journal: J Inherit Metab Dis Date: 1992 Impact factor: 4.982
Authors: Cornelia Laule; Irene M Vavasour; Shannon H Kolind; David K B Li; Tony L Traboulsee; G R Wayne Moore; Alex L MacKay Journal: Neurotherapeutics Date: 2007-07 Impact factor: 7.620
Authors: Anna Hood; Jo Ann V Antenor-Dorsey; Jerrel Rutlin; Tamara Hershey; Joshua S Shimony; Robert C McKinstry; Dorothy K Grange; Shawn E Christ; Robert Steiner; Desiree A White Journal: Mol Genet Metab Date: 2014-11-13 Impact factor: 4.797
Authors: T Scarabino; T Popolizio; M Tosetti; D Montanaro; G M Giannatempo; R Terlizzi; S Pollice; A Maiorana; N Maggialetti; A Carriero; V Leuzzi; U Salvolini Journal: Radiol Med Date: 2009-03-10 Impact factor: 3.469
Authors: Jo Ann V Antenor-Dorsey; Tamara Hershey; Jerrel Rutlin; Joshua S Shimony; Robert C McKinstry; Dorothy K Grange; Shawn E Christ; Desirée A White Journal: Mol Genet Metab Date: 2013-04-06 Impact factor: 4.797
Authors: Renzo Manara; Alessandro P Burlina; Valentina Citton; Mario Ermani; Francesco Vespignani; Carla Carollo; Alberto B Burlina Journal: Neuroradiology Date: 2009-08-04 Impact factor: 2.804
Authors: Desirée A White; Jo Ann V Antenor-Dorsey; Dorothy K Grange; Tamara Hershey; Jerrel Rutlin; Joshua S Shimony; Robert C McKinstry; Shawn E Christ Journal: Mol Genet Metab Date: 2013-07-19 Impact factor: 4.797