WHITE-MATTER ABNORMALITIES IN PATIENTS WITH TREATED HYPERPHENYLALANINEMIA - MAGNETIC-RESONANCE RELAXOMETRY AND PROTON SPECTROSCOPY FINDINGS

In order to further clarify the pathogenesis and clinical significance of MRI white matter abnormalities in treated hyperphenylalaninaemia (HPA), ten patients (seven type I HPA, two type Il and one type III) underwent T-2 relaxometry (n = 8) and/or H-1 spectroscopy (n = 7) in addition to conventional MR spin-echo imaging at 1.5 T. Two patients with severe MRI abnormalities had repeat examinations during and after a 6- to 8-month period of strict diet control. The clinical evaluation included a detailed neurological examination. In nine out of ten patients visual evoked potentials (VEP) were obtained parallel to the MR examination. MR imaging demonstrated typical symmetrical areas of prolonged T-2 relaxation time predominantly in the posterior periventricular white matter in all but one of type I and Il patients. There was no consistent relationship between MRI findings and time of diagnosis/initiation of therapy, IQ or visual evoked potential changes. MRI abnormalities tended to be more severe in patients with poor dietary control and high current plasma phenylalanine levels, whereas a normal MRI was found only in patients with plasma phenylalanine levels continuously below 0.36 mmol/l. There was marked regression of MRI abnormalities already after 3 months of strict diet control. T-2 relaxometry showed a bi-exponential behaviour of T-2 in the affected white matter, with a slow component of about 200-450 ms, indicating an increase in free (extracellular) water. H-1 spectroscopy revealed no signs of severe neuronal damage. We conclude, that the observed white matter changes in treated HPA probably represent reversible structural myelin changes rather than permanent demyelination.