MAGNETIC-RESONANCE-IMAGING IN PHENYLKETONURIA - REVERSAL OF CEREBRAL WHITE-MATTER CHANGE

Objectives: To investigate the extent to which the abnormalities in cerebral white matter in adolescents and adults with phenylketonuria (PKU) are reversible. Method: Magnetic resonance imaging (MRI), of the brain was repeated in 41 patients with PKU (age range, 14 to 49 years) after an interval (median, 9 months; range, 3 to 12 months) of dietary intervention, Scans were scored according to the extent of the white matter involvement, After an initial MRI, five patients returned to a strict low-phenylalanine diet with amino acid supplement; 21 patients started a low-protein diet (1 gm/kg) with amino acid supplement; and 15 patients made no dietary alteration. Results: Scans improved in all five patients who returned to a strict low-phenylalanine diet, in 5 of the 21 patients on the low-protein diet plus amino acid supplement, and in 4 of the 15 patients who made no dietary change, There was a significant association between change in the MRI findings and in the blood phenylalanine concentration (Pearson correlation: r = 0.55; p <0.0002) and between change in the MRI and in the phenylalanine level at the time of the second scan (r = 0.58; p <0.0001). Improvement was seen primarily in those in whom phenylalanine levels were reduced to less than 900 mu mol/L. There was no obvious change in MRI score after 3 weeks of strict phenylalanine restriction for the two adults who underwent serial scanning. Conclusion: The MRI changes in PKU are at least partially reversible by lowering the blood phenylalanine concentration.