MR in phenylketonuria-related brain lesions.

PURPOSE: Phenylketonuria (PKU) patients were examined by different MR techniques to explain the pathological changes observed in periventricular white brain matter using conventional MR imaging. MATERIAL AND METHODS: Fifteen patients with treated classical PKU were examined by 1H spectroscopy, relaxometry and diffusion imaging on a whole-body 1.5-T MR imager. RESULTS: Known PKU lesions characterized by T2 enhancement in periventricular white matter were observed in all patients. The MR spectra from the lesioned areas showed a significant decrease in choline concentration. The mean ADC of water decreased and tortuosity increased in PKU lesions compared to control data. CONCLUSION: The results support the following hypothesis: The T2 increase in the PKU lesion reflects a raised concentration of free water molecules (about 15%) that have an increased trajectory between collisions compared to the same region in controls. The increase in water mobility might be explained by changes in extracellular space volume and myelin sheaths, which, presumably, have a different geometry with more hydrophobic sites in PKU patients. The changes result in increased tortuosity and may be confirmed by the loss of anisotropy in PKU lesions.

Decreasing choline signal--a marker of phenylketonuria?

We found a statistically significant increase in the N-acetylaspartate/choline-containing compounds (NAA/Cho) ratio in a group of 69 phenylketonuria (PKU) patients with a rise in echo time (TE) compared with a group of 35 age-matched controls. The absolute concentration of creatine did not differ significantly between patients and controls, but a significant difference was found for choline-containing compounds (1.33 mM in patients vs. 1.53 mM in controls, p < 0.0209). The change in NAA/Cho (for TE = 270 ms: 2.52 in patients vs. 1.96 in controls, p270 < 0.0001) can be explained by a significant difference in T2 values of choline compounds between patients and controls. This result shows that the difference in the ratios of signal intensities often used for the description of different pathologies can be explained not only by changes in the absolute metabolite concentration but also by changes in the mobility reflected by relaxation times.

Long-term follow-up of patients treated for phenylketonuria (PKU). Results from the Prague PKU Center.

In order to examine the association between treatment parameters and intellectual outcome, a total of 58 adolescents with phenylketonuria (PKU) treated at the PKU center of the Department of Pediatrics at the University of Prague were tested at the age of 15 years with the Prague Child Wechsler Test. Patients were classified into three groups with different levels of dietary control that remained relatively stable over time at mean phenylalanine levels of 360, 540 and 680 mumol/l. The mean level of phenylalanine was highly correlated with IQ and school education. Patients with mean phenylalanine levels of < or = 360 mumol/l had near-normal level. Initial experience with eight cases of maternal PKU underlines the necessity for a strict treatment regimen, which must be started pre-conception in order to prevent the fetus from developmental damage.

Proton in vivo spectroscopy of patients with hyperphenylalaninaemia.

Changes in MR images and 1H spectra of 20 patients with hyperphenylalaninaemia were compared with data of controls. Major changes in T2 MR images were found in the periventricular area (20/19). Some patients showed lesions in MR images of basal ganglia (20/7) and in the cerebellum (20/4). The results of proton MR spectroscopy show no significant difference for NAA/Cr ratios but significant ones between the ratios of NAA/Cho (p = 0.97) and Cho/Cr (p = 0.98) of controls and patients with hyperphenylalaninaemia.

[Blood somatomedin levels in neonates with congenital hypothyroidism and phenylketonuria]. / Hladiny sérového somatomedinu u novorozencu s kongenitální hypotyreózou a fenylketonurií.

A biological method was employed for assessing the somatomedin activity (SM)-IGF I-somatomedin C: 1) in 13 10 to 23-day old children with congenital hypothyroidism (CH) before starting substitution therapy with L-thyroxine and after one month lasting therapy. SM levels were significantly lower prior to the onset of therapy than in a control group (for p less than 0.01 on 1% level). The SM levels in treated children did not differ from controls. 2) 16 children with classic phenylketonuria (PKU) were also examined of the age of 12-23 days before starting dietary treatment with restricted phenylalanine (Phe). When compared with a control group SM levels were significantly lower in the PKU group (p = 0.01 on 5% level). When stable serum Phe concentrations had been obtained, following restricted Phe intake, SM levels no longer differed from the control. However statistical correlation of Phe and SM levels was not attained.