Background and purpose: Our purpose was to specify the most severely affected brain structures in early treated phenylketonuria regarding volume loss and establish possible correlations between volume loss and plasma levels of phenylalanine (Phe).
Methods: In 31 patients with early treated phenylketonuria and in 27 healthy volunteers, we acquired volumetric MR imaging data. Serum Phe concentrations at different times were measured as well. Semiautomatic volumetric postprocessing of the cerebellum, cerebrum (supratentorial brain tissue), hippocampus, intracranial volume, lateral ventricles, nucleus caudatus, nucleus lentiformis, pons, and thalamus, as well as the two-dimensional extension of the corpus callosum, was performed using the software BRAINS2. For each separate brain structure, the relative differences between the normal and the phenylketonuria group (delta(rel)) were calculated.
Results: The cerebrum, corpus callosum, hippocampus, intracranial volume, and pons were significantly smaller in patients with phenylketonuria than in healthy patients. The volume of the lateral ventricles was significantly larger in patients with phenylketonuria than in healthy ones. The most severely affected structures were the pons (delta(rel) = 16%), hippocampus (delta(rel) = 14.5%), cerebrum (delta(rel) = 13%), and corpus callosum (delta(rel) = 10%). No significant differences were found for the basal ganglia, cerebellum, and thalamus. There were no significant correlations found between the volume of any of the different brain structures and the metabolic parameters.
Conclusion: The most severely affected brain structures in early-treated patients with phenylketonuria regarding volume loss are the cerebrum, corpus callosum, hippocampus, and pons.