International Scholarly Research Network ISRN Pediatrics Volume 2012, Article ID 976206, 4 pages doi:10.5402/2012/976206 Research Article The Association between EEG Abnormality and Behavioral Disorder: Developmental Delay in Phenylketonuria Parvaneh Karimzadeh, 1 Mohammad Reza Alaee, 2 and Hadi Zarafshan 3 1 Pediatric Neurology, Pediatric Neurology Research Center, Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran 2 Pediatric Endocrinology, Pediatric Neurology Research Center, Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran 3 Pediatric Neurology Research Center, Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran Correspondence should be addressed to Parvaneh Karimzadeh, pkarimzadeh@sbmu.ac.ir Received 20 December 2011; Accepted 24 January 2012 Academic Editors: G. Deda and A. Maheshwari Copyright © 2012 Parvaneh Karimzadeh et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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, con- sequently, 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 tyro- sine. In deficiency of this enzyme, phenylpyruvate (phenyl- ketone) 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 bet- ween 600 μmol/L and 1200 μmol/L. In mild hyperphenylala- ninemia, Phe level is higher than normal limits, but below 600 μmol [1, 2]. In early infants with phenylketonuria, the serum pheny- lalanine 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 lead- ing 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 of metabolism such as PKU and other similar disorders, the exact neurodysfunction defect is not clearly definite [1–3]. Hyperphenylalaninemia may be simply detected in the newborn screening test. Clinical manifestations in untreated infants with PKU include growth failure, microcephaly, sei- zures, dermatitis, and intellectual defect. Remarkable clinical findings are light colored skin, hair and eyes, eczematous rash and behavioral disorders [1–4]. Different studies reported 25% generalized or partial sei- zures in phenylketonuria. Infantile spasms and myoclonic seizures are highly reported [4].