title: A case of early onset epileptic encephalopathy with de novo mutation in SLC35A2: Clinical features and treatment for epilepsy.
abstract: BACKGROUND
  Mutations of SLC35A2 that encodes Golgi-localized Uridine diphosphate (UDP)-galactose transporter at Xp11.23 lead to congenital disorders of glycosylation (CDG). Although patients with CDG generally have diverse systemic symptoms, patients with a SLC35A2 mutation manifest predominantly disorders of the central nervous system (CNS).
  
  
  METHODS
  A female infant aged 12months was referred to our center because of intractable seizures. The patient was born with birth weight of 3228g after 40weeks of unremarkable gestation. At the age of 2months, she had partial seizures evolving to epileptic spasms. Her electroencephalogram showed hypsarrhythmia. Her seizures were refractory to antiepileptic drugs. At referral to our center at 12months, she had developmental delay (no head control), widely spaced inverted nipples, external strabismus, and bilateral heterochromia of irises. Blood examinations were normal. Brain magnetic resonance imaging findings included cerebral and cerebellar atrophy, thinning of the corpus callosum, and arachnoid pouch. Whole-exome sequencing detected a de novo frameshift mutation c.950delG (p.Gly317Alafs*32) at exon 4 in SLC35A2. Seizures subsided after the second adrenocorticotropic hormones (ACTH) therapy at 18months. At the age of 36months, although she had intellectual disability with no meaningful words, she was seizure-free and was able to sit without support and showed smiling face a lot.
  
  
  CONCLUSIONS
  This report reviewed the clinical features of patients with a SLC35A2 mutation. ACTH therapy may be effective for refractory epilepsy in these patients.
authors.affiliation: Department of Pediatrics, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, NHO, Japan. Electronic address: kimizu-osk@umin.ac.jp.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Kimizu
authors.affiliation: Department of Pediatrics, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, NHO, Japan.
authors.forename: Yukitoshi
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Department of Pediatrics, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, NHO, Japan.
authors.forename: Taikan
authors.initials: T
authors.lastname: Oboshi
authors.affiliation: Department of Pediatrics, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, NHO, Japan.
authors.forename: Asako
authors.initials: A
authors.lastname: Horino
authors.affiliation: Department of Pediatrics, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, NHO, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Koike
authors.affiliation: Department of Pediatrics, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, NHO, Japan.
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Yoshitomi
authors.affiliation: Department of Pediatrics, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, NHO, Japan; Department of Pediatrics, Graduate School of Medical Sciences Tokushima University, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Mori
authors.affiliation: Department of Pediatrics, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, NHO, Japan.
authors.forename: Tokito
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Department of Pediatrics, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, NHO, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ikeda
authors.affiliation: Department of Clinical Genetics, Osaka Medical Center and Research Institute for Maternal and Child Health, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Okamoto
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Japan.
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Nakashima
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Japan.
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Saitsu
authors.affiliation: Department of Pediatrics, Showa University School of Medicine, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Kato
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
authors.affiliation: Department of Pediatrics, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, NHO, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Imai
mesh_terms: D017668:Age of Onset; D001927:Brain Diseases / Q000209:etiology*; D018981:Congenital Disorders of Glycosylation / Q000175:diagnosis / Q000235:genetics; D004569:Electroencephalography / Q000379:methods; D004827:Epilepsy / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy*; D005260:Female; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging / Q000379:methods; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D013036:Spasms, Infantile / Q000175:diagnosis / Q000209:etiology / Q000235:genetics; D000099237:UDP-Galactose Translocators
chemical_list: D009004:Monosaccharide Transport Proteins; D000099237:UDP-Galactose Translocators
keywords: ACTH therapy; CDG; Early onset epileptic encephalopathy; SLC35A2; Skewed X-inactivation