title: A novel R275X mutation of the SLC25A15 gene in a Japanese patient with the HHH syndrome.
abstract: The hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome (MIM 238970) is an autosomal recessive metabolic disorder caused by a deficiency of the mitochondrial ornithine transporter, one of the urea cycle components. Mutations in the SLC25A15 gene have been coupled to the HHH syndrome. We describe a Japanese female patient with the HHH syndrome due to a novel homozygous R275X SLC25A15 mutation and male sibling who presumably carried the same mutation. He exhibited slowly progressive deterioration with seizures, a gait disturbance due to polyneuropathy, episodic confusion, and died of acute encephalopathy at 34 years of age while the proband exhibited moderate mental retardation, seizures, mild spastic paraplegia, and deafness without neurological deterioration for more than 20 years. The clinical features of previously documented patients with the homozygous SLC25A15 mutation demonstrated that genotype did not simply correlate with clinical severity. The phenotypic variability might depend on other factors, such as dietary and other genetic ones.
authors.affiliation: Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. htorys@pediatr.med.kyushu-u.ac.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Torisu
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Kira
authors.forename: Naomi
authors.initials: N
authors.lastname: Kanazawa
authors.forename: Megumi
authors.initials: M
authors.lastname: Takemoto
authors.forename: Masafumi
authors.initials: M
authors.lastname: Sanefuji
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Sakai
authors.forename: Seiichi
authors.initials: S
authors.lastname: Tsujino
authors.forename: Toshiro
authors.initials: T
authors.lastname: Hara
mesh_terms: D000328:Adult; D000592:Amino Acid Metabolism, Inborn Errors / Q000150:complications / Q000235:genetics*; D026923:Amino Acid Transport Systems, Basic; D001120:Arginine / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D006801:Humans; D022124:Hyperammonemia / Q000235:genetics; D007564:Japan / Q000208:ethnology; D008297:Male; D028361:Mitochondrial Diseases / Q000150:complications / Q000235:genetics*; D033681:Mitochondrial Membrane Transport Proteins; D009154:Mutation; D011506:Proteins / Q000235:genetics*
chemical_list: D026923:Amino Acid Transport Systems, Basic; D033681:Mitochondrial Membrane Transport Proteins; D011506:Proteins; C442901:SLC25A15 protein, human; D001120:Arginine