title: Molecular diagnosis of mitochondrial respiratory chain disorders in Japan: focusing on mitochondrial DNA depletion syndrome.
abstract: BACKGROUND
  Although mitochondrial respiratory chain disorders (MRCD) are one of the most common congenital metabolic diseases, there is no cumulative data on enzymatic diagnosis and clinical manifestation for MRCD in Japan and Asia.
  
  
  METHODS
  We evaluated 675 Japanese patients having profound lactic acidemia, or patients having symptoms or signs of multiple-organ origin simultaneously without lactic acidemia on respiratory chain enzyme activity assay and blue native polyacrylamide gel electrophoresis. Quantitative polymerase chain reaction was used to diagnose mitochondrial DNA depletion syndrome (MTDPS). Mutation analysis of several genes responsible for MTDPS was also performed.
  
  
  RESULTS
  A total of 232 patients were diagnosed with a probable or definite MRCD. MRCD are common, afflicting one in every several thousand people in Japan. More than one in 10 of the patients diagnosed lacked lactic acidemia. A subsequent analysis of the causative genes of MTDPS identified novel mutations in six of the patients. A 335 bp deletion in deoxyguanosine kinase (DGUOK; g.11692_12026del335 (p.A48fsX90)) was noted in two unrelated families, and may therefore be a common mutation in Japanese people. The proportion of all patients with MTDPS, and particularly those with recessive DNA polymerase γ (POLG) mutations, appears to be lower in Japan than in other studies. This is most likely due to the relatively high prevalence of ancient European POLG mutations in Caucasian populations. No other significant differences were identified in a comparison of the enzymatic diagnoses, disease classifications or prognoses in Japanese and Caucasian patients with MRCD.
  
  
  CONCLUSIONS
  MTDPS and other MRCD are common, but serious, diseases that occur across all races.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Saitama Medical University, Saitama, Japan; Murdoch Childrens Research Institute, Royal Children's Hospital and Department of Paediatrics, University of Melbourne, Melbourne, Australia.
authors.forename: Taro
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Kei
authors.initials: K
authors.lastname: Murayama
authors.forename: Alison G
authors.initials: AG
authors.lastname: Compton
authors.forename: Canny
authors.initials: C
authors.lastname: Sugiana
authors.forename: Hiroko
authors.initials: H
authors.lastname: Harashima
authors.forename: Shin
authors.initials: S
authors.lastname: Amemiya
authors.forename: Masami
authors.initials: M
authors.lastname: Ajima
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tsuruoka
authors.forename: Ayako
authors.initials: A
authors.lastname: Fujinami
authors.forename: Emi
authors.initials: E
authors.lastname: Kawachi
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Kurashige
authors.forename: Kenshi
authors.initials: K
authors.lastname: Matsushita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wakiguchi
authors.forename: Masato
authors.initials: M
authors.lastname: Mori
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Iwasa
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okazaki
authors.forename: David R
authors.initials: DR
authors.lastname: Thorburn
authors.forename: Akira
authors.initials: A
authors.lastname: Ohtake
mesh_terms: D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007418:Intestinal Pseudo-Obstruction / Q000175:diagnosis*; D007564:Japan; D028361:Mitochondrial Diseases / Q000175:diagnosis*; D017237:Mitochondrial Encephalomyopathies / Q000175:diagnosis*; D025202:Molecular Diagnostic Techniques; D039141:Muscular Dystrophy, Oculopharyngeal; D009886:Ophthalmoplegia / Q000151:congenital
keywords: DGUOK deletion mutation; enzymatic diagnosis; mitochondrial DNA depletion syndrome; mitochondrial respiratory chain disorder; racial difference