Magnetic resonance imaging of the brain in adolescents with phenylketonuria and in one case of 6-pyruvoyl tetrahydropteridine synthase deficiency

Abstract

White matter abnormalities on MRI have been observed in phenylketonuria (PKU) patients with late onset neurological symptoms as well as in neurologically inconspicious patients. We investigated 14 early treated adolescents at an age between 12 and 17 years (mean age 14.3 years) with classical PKU as well as one retarded patient with atypical PKU by cranial MRI with spinecho T1-, T2- and proton density sequences. Clinical examination was normal. Visual evoked potential (VEP) examination showed a prolonged latency of peak P100 (mean 122.6 ms; control mean 115.9) and IQ testing showed a mean IQ of 101.1. To investigate the influence of plasma phenylalanine (Phe) levels three approaches were used: Phe was determined for the day of MRI, for a period of 6 months prior to MRI and for lifetime up to 12 years. MRI scans revealed areas of abnormally increased signal intensity on T2-weighted and proton density images in 12 (86%) patients, preferably involving the parieto-occipital lobes. MRI of the patient with atypical PKU was normal. MRI findings correlated most strongly to long-term dietary control up to 12 years. We found no correlation with the other parameters of biochemical control, IQ or VEP latency. The nature and prognosis of MRI abnormalities in neurologically normal PKU patients remain unclear although abnormalities in VEPs which were not associated with the degree of MRI abnormalities in our sample indicate a disturbance in myelination along the visual pathways.

Rationale for the German recommendations for phenylalanine level control in phenylketonuria 1997

“…Magnetic resonance imaging, magnetic resonance spectroscopy, and positron emission tomography Abnormal signal intensity on MRI is most marked in the occipital-parietal regions and in more severe cases extends into the frontal and temporal lobes, basal ganglia, brainstem or the cerebellum [13,55,56,79]. Partial reversibility after 2 to 3 months of continuous reduction of Phe levels below 360±900 lmol/L (6±15 mg/dL) has been observed irrespective of the interval o treatment preceding the scan [5,13].…”

Función neuropsicológica en la fenilcetonuria tratada precozmente: Una revisión

“…En estudios se ha intentado descubrir qué anomalías de la sustancia blanca no se correlacionan significativamente con la inteligencia general (CI) [104,105,107,108,[114][115][116] . No obstante, puede requerirse cierto grado de patología antes de que las anomalías de la sustancia blanca deterioren la función [5,44] .…”

Altérations neuropsychologiques chez les patients phénylcétonuriques traités précocement: Revue

“…Ainsi, des études indiquent que les anomalies de la substance blanche ne seraient pas significativement corrélées avec l'intelligence globale (QI) [104,105,107,108,[114][115][116] . Cependant, il semblerait que la pathologie doit être à un stade suffisamment avancé pour que les anomalies de la substance blanche altèrent les fonctions [5,44] .…”