J GM Journal of Genetic Medicine retardation, and bulbar/pseudobulbar signs. The recent study showed that these clinical symptoms and signs may vary according to age at onset and GFAP mutation site. 2) This study by Prust et al. includes a review of 218 cases, includ- ing 30 new cases of Alexander disease, with evidence suggesting that early age of onset (often before 4 years) is frequently asso- ciated with seizures, macrocephaly, encephalopathy, paroxysmal deterioration, or failure to thrive. However, only a few studies emphasizes in distinguishing a neonatal form of Alexander disease from early onset type where specific clinical symptoms exhibit during neonatal period. 3,4) The neonatal form can be distinguished from others by frequent intractable seizures in A Neonatal Form of Alexander Disease Presented with Intractable Seizures and Obstructive Hydrocephalus Il Han Yoo 1 , Won Gi Hong 1 , Hunmin Kim 2 , Byung Chan Lim 1 *, Hee Hwang 2 , Jong-Hee Chae 1,3 , Ki Joong Kim 1,2 and Yong Seung Hwang 1,2 1 Pediatric Clinical Neuroscience Center, Department of Pediatrics, Seoul National University Children’s hospital, Seoul, Korea 2 Department of Pediatrics, Seoul National University Bundang Hospital, Gyeonggi-do, 3 Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea Case Report J Genet Med 2013;10(2):113-116 http://dx.doi.org/10.5734/JGM.2013.10.2.113 ISSN 1226-1769(Print) 2233-9108(Online) Alexander disease is a rare degenerative leukodystrophy caused by dominant mutations in glial fbrillary acidic protein ( GFAP). The neonatal form of Alexander disease may manifest as frequent and intractable seizures or obstructive hydrocephalus, with rapid progression leading to severe disability or death within two years. We report a case of a 50-day-old male who presented with intractable seizures and obstructive hydrocephalus. His initial magnetic resonance imaging (MRI) suggested a tumor-like lesion in the tectal area causing obstructive hydrocephalus. Despite endoscopic third ventriculostomy and multiple administrations of antiepileptic drugs, the patient experienced intractable seizures with rapid deterioration of his clinical status. After reviewing serial brain MRI scans, Alexander disease was suspected. Subsequently, we confrmed the de novo missense mutation in GFAP (c.1096T>C, Y366H). Although the onset was slightly delayed from the neonatal period (50 days old), we concluded that the overall clinical features were consistent with the neonatal form of Alexander disease. Furthermore, we also suspected that a Y366 residue might be closely linked to the neonatal form of Alexander disease based on a literature review. Key words: Alexander disease, GFAP mutation, Hydrocephalus, Seizure Introduction Alexander disease, first described by W. Stewart Alexander in 1949, 1) is a rare neurodegenerative disorder caused by dominant mutations in the glial fbrillary acidic protein ( GFAP ) gene. These mutations produce a gain of function in a GFAP protein leading to astrocyte dysfunction, deposition of Rosenthal fibers, and abnormal intracytoplasmic inclusions in astrocytes. Although this rare leukoencephalopathy has been well known for its frequent associations with macrocephaly or megalencephaly, the clinical presentation is rather non-specifc, including seizures, hydrocephalus, megalencephaly, progressive psychomotor Received: 23 August 2013, Revised: 23 September 2013, Accepted: 26 September 2013, Published: 31 December 2013 *Corresponding author: Byung Chan Lim, M.D. Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea Tel: +82-2-2072-2364, Fax: +82-2-743 3455, E-mail: prabbit7@snu.ac.kr *Confict of interest: We declare that we do not have any conficts of interests. ㏄ This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. c Copyright 2013 by the Korean Society of Medical Genetics www.e-kjgm.org