Brain MRI diffusion-weighted imaging in patients with classical phenylketonuria

Introduction: The aim of this study was to grade magnetic resonance white matter abnormalities (WMAs) of classical phenylketonuria (cPKU) patients treated from birth and to compare sensitivity and specificity of T2-weighted and diffusion-weighted images (DWI). Methods: Twenty early-treated cPKU patients still on a low-phenylalanine diet (12 males; mean age 21.2 years) and 26 normal subjects (ten males; mean age 25.1 years) were enrolled. Typical T2- and diffusion-weighted WMAs were semiquantitatively graded according to Thompson score (TS). Besides, a regional magnetic resonance imaging (MRI) score (mTS) was developed according to extension and intensity of WMAs. Phenylalanine and tyrosine plasma concentrations before performing MRI and the amino acid mean levels collected the year before MRI (Tyr_year and Phe_year) were measured. Results: No patient with Phe_year concentration below 460 μmol/L showed WMAs. In cPKU patients, TS and mTS were significantly higher on DWI than on T2 images (3.50 vs 2.65 and 23.65 vs 15.85, respectively, p <0.002, Wilcoxon test). All controls were scored 0 on DWI, while in T2 images, TS and mTS were 0.19 and 1.70. DWI evaluated by mTS disclosed a frontotemporal, occipital, and parietal WM progressive involvement. TS and mTS, both on T2 images and on DWI, showed no correlation with tyrosine while they proved to have a strong correlation with phenylalaninemia and an excellent one with Phe_year levels. Conclusion: Among the different MR sequences, DWI seems to be the most sensitive and reliable in detecting and grading the typical WMAs of cPKU patients.