title: A wide spectrum of clinical and brain MRI findings in patients with SLC19A3 mutations.
abstract: BACKGROUND
  SLC19A3 (solute carrier family 19, member 3) is a thiamin transporter with 12 transmembrane domains. Homozygous or compound heterozygous mutations in SLC19A3 cause two distinct clinical phenotypes, biotin-responsive basal ganglia disease and Wernicke's-like encephalopathy. Biotin and/or thiamin are effective therapies for both diseases.
  
  
  METHODS
  We conducted on the detailed clinical, brain MRI and molecular genetic analysis of four Japanese patients in a Japanese pedigree who presented with epileptic spasms in early infancy, severe psychomotor retardation, and characteristic brain MRI findings of progressive brain atrophy and bilateral thalami and basal ganglia lesions.
  
  
  RESULTS
  Genome-wide linkage analysis revealed a disease locus at chromosome 2q35-37, which enabled identification of the causative mutation in the gene SLC19A3. A pathogenic homozygous mutation (c.958G > C, [p.E320Q]) in SLC19A3 was identified in all four patients and their parents were heterozygous for the mutation. Administration of a high dose of biotin for one year improved neither the neurological symptoms nor the brain MRI findings in one patient.
  
  
  CONCLUSIONS
  Our cases broaden the phenotypic spectrum of disorders associated with SLC19A3 mutations and highlight the potential benefit of biotin and/or thiamin treatments and the need to assess the clinical efficacy of these treatments.
authors.affiliation: Department of Genetics, Institute for Developmental Research, Aichi Human Service Center, Aichi, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Yamada
authors.forename: Kiyokuni
authors.initials: K
authors.lastname: Miura
authors.forename: Kenju
authors.initials: K
authors.lastname: Hara
authors.forename: Motomasa
authors.initials: M
authors.lastname: Suzuki
authors.forename: Keiko
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kumagai
authors.forename: Naoko
authors.initials: N
authors.lastname: Ishihara
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Yamada
authors.forename: Ryozo
authors.initials: R
authors.lastname: Kuwano
authors.forename: Shoji
authors.initials: S
authors.lastname: Tsuji
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Wakamatsu
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics; D001480:Basal Ganglia Diseases / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D001710:Biotin / Q000627:therapeutic use; D001921:Brain / Q000473:pathology*; D002648:Child; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D009154:Mutation; D013831:Thiamine / Q000627:therapeutic use; D014899:Wernicke Encephalopathy / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*
chemical_list: D026901:Membrane Transport Proteins; C492291:SLC19A3 protein, human; D001710:Biotin; D013831:Thiamine