title: Triple A syndrome in Japan.
abstract: BACKGROUND
  Triple A syndrome is an autosomal recessive disease, characterized by esophageal achalasia, alacrima, and adrenal insufficiency, as well as involvement of the central, peripheral, and autonomic nervous systems. This disease mimics amyotrophic lateral sclerosis in some patients. The causative gene encodes ALADIN, a nuclear pore complex (NPC) component. Only 5 patients have been reported in Japan.
  
  
  METHODS
  We conducted the first nationwide survey of triple A syndrome. Identified mutants were expressed as GFP-fusion proteins in cultured cells.
  
  
  RESULTS
  Two new patients were identified, and 1 had a novel mutation (p.Ser182fsX19). All mutant proteins tested were mislocalized from NPC to cytoplasm.
  
  
  CONCLUSIONS
  The most consistent neurological manifestation of triple A syndrome in Japanese patients was progressive bulbospinal muscular atrophy with both upper and lower motor neuron involvement, which mimicked motor neuron disease, similar to that seen in patients in Western countries. The identification of the new patients suggests that more cases are undiagnosed in Japan.
authors.affiliation: Department of Neurology, Nara Medical University School of Medicine, Kashihara, Nara, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Ikeda
authors.forename: Makito
authors.initials: M
authors.lastname: Hirano
authors.forename: Keiich
authors.initials: K
authors.lastname: Shinoda
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Katsumata
authors.forename: Daisuke
authors.initials: D
authors.lastname: Furutama
authors.forename: Katsuya
authors.initials: K
authors.lastname: Nakamura
authors.forename: Shu-Ichi
authors.initials: S
authors.lastname: Ikeda
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Tanaka
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Hanafusa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kitajima
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kohno
authors.forename: Mizuho
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Yusaku
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ueno
mesh_terms: D000293:Adolescent; D000309:Adrenal Insufficiency / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D000328:Adult; D002675:Child, Preschool; D003593:Cytoplasm / Q000378:metabolism; D004931:Esophageal Achalasia / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D005260:Female; D056726:Genetic Association Studies; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells / Q000378:metabolism / Q000648:ultrastructure; D006306:Health Surveys; D006801:Humans; D007564:Japan; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D028861:Nuclear Pore Complex Proteins / Q000235:genetics; D018709:Statistics, Nonparametric; D011795:Surveys and Questionnaires; D014162:Transfection
chemical_list: C416506:AAAS protein, human; D009419:Nerve Tissue Proteins; D028861:Nuclear Pore Complex Proteins; D049452:Green Fluorescent Proteins
keywords: AAA; motor neuron disease; nationwide survey; nuclear pore complex; triple A syndrome