The Association between EEG Abnormality and Behavioral Disorder: Developmental Delay in Phenylketonuria

Background. Brain defect leading to developmental delay is one of the clinical manifestations of phenylketonuria. The aim of this study was to evaluate the association between EEG abnormality and developmental delay/behavioral disorders in phenylketonuria. Patients and Methods. 105 phenylketonuria patients, who were diagnosed through newborn screening tests or during follow-up evaluation, were enrolled. Patients who were seizure-free for at least six months before the study were included. The developmental score were evaluated by the ASQ questionnaire (age-stage questionnaire) and the test of child symptom inventory-4 (CSI-4), respectively. Results. 55 patients had a history of seizure more than 6 months before the study. Seventy had abnormal EEG (cases) and 35 had normal EEG (controls). There was no significant difference between mean phenylalanine levels in the abnormal and normal EEG groups at the time of diagnosis, after six months and at our evaluation. Distribution of DQ level in the abnormal and normal EEG groups revealed a significant difference. An abnormal EEG was associated with a higher percentage of low DQ levels. Conclusion. Paroxysmal epileptic discharges in PKU patients are important. Treatment of these EEG abnormalities may affect developmental scores or may lead to correction of some behavioral disorders in patients. 1. Introduction Phenylketonuria is an autosomal recessive metabolic disease which may cause brain insult in the developing brain, consequently, leading to progressive neurodevelopmental delay. In this genetic metabolic disorder, the hepatic enzyme, phenylalanine hydroxylase (PAH), is missing. This enzyme is necessary to break down amino acid phenylalanine to tyrosine. In deficiency of this enzyme, phenylpyruvate (phenylketone) may be detected in the urine [1]. Phenylketonuria is classified into classic phenylketonuria (PKU) which indicates phenylalanine (Phe) levels higher than 1200？μmol/L and mild PKU in which Phe levels are between 600？μmol/L and 1200？μmol/L. In mild hyperphenylalaninemia, Phe level is higher than normal limits, but below 600？μmol [1, 2]. In early infants with phenylketonuria, the serum phenylalanine level is in normal limits at birth, but begins to rise within the first few hours of life. Excessive phenylalanine is generally believed to be responsible for the brain insult leading to progressive mental retardation and seizure disorder. Without treatment, cognitive delay becomes evident within 6 months of age and is progressive [1, 2]. Although the principal biochemical defect is obvious in inborn errors