Evaluation of the correlation of brain MR volumetric measurements with the clinical course of the patients, the age of onset of treatment, and treatment regimens in patients with phenylketonuria

Aim: The aim of this retrospective study is to evaluate the correlation of brain volumetric measurements in Phenylketonuria (PKU) with the normal population, clinical course of patients, age at onset of treatment, and treatment compliance. Materials and Methods: Thirty-three PKU patients who were diagnosed or followed up in Çukurova University Faculty of Medicine, Department of Pediatric Nutrition and Metabolism and underwent brain magnetic resonance (MR) imaging in the Department of Radiology between 2014 and 2018, and a control group of 26 participants were included in the study. Patients' gender, date of birth, age at diagnosis, hyperphenylalaninemia types, blood phenylalanine (Fa) level during MRI, WISC-R IQ score and diet compliance were recorded. Brain volumetric measurements were made by using a software program (Olea Sphere, Version 3) of MR images taken from the image archive of our hospital. Results: The study group of 33 patients diagnosed with PKU and the control group consisting of 26 participants with normal brain MRI findings were included in the study. Of the patients in the study group, 14 were female and 19 were male; of those in the control group, 18 were female and 8 were male. The mean age of the patients in the study group was 12.6±4.1, and the mean age of the participants in the control group was 13.0±3.9. It was found that mean values of right and left frontal lobe, temporal lobe, occipital lobe, cerebral hemisphere, gray matter, white matter, cerebellum, thalamus, caudate nucleus and left lentiform nucleus volume in PKU patients were lower than those in the control group (p<0,05). No significant difference was found between the study and control groups in the volumetric measurements of the mesencephalon, pons and bulb (p>0.05). A positive (linear) moderate correlation was found between the serum Fa level measured during MRI in PKU patients and the volume of gliotic brain tissue in the right and left hemisphere periventricular white matter (respectively r=0,546; r=0,537). In the PKU group, there was a positive (linear) moderate correlation between the WISC-R IQ score and the age (months) at the time of diagnosis. Serum Fa levels measured during MRI were significantly higher in the classical PKU group and in diet-incompatible patients compared to the other groups (p<0,05). Conclusion: Our study revealed that brain volume (cerebrum, cerebral gray and white matter, and cerebellum) and deep gray matter volume (thalamus, nucleus caudatus, and nucleus lentiformis) in PKU patients were significantly less than in healthy controls. This result led us to conclude that cerebral and cerebellar gray matter and basal ganglia are also involved in the pathophysiology of neurological abnormalities in PKU. While early diagnosis and treatment in PKU are associated with higher IQ; higher serum Fa levels are associated with lower IQ and abnormal MRI findings. Keywords: Phenylketonuria, brain MRI, brain volumetry, diet.