title: Clinical, biochemical and molecular investigation of adult-onset glutaric acidemia type II: Characteristics in comparison with pediatric cases.
abstract: BACKGROUND
  An increasing number of adult patients have been diagnosed with fatty acid β-oxidation disorders with the rising use of diagnostic technologies. In this study, clinical, biochemical, and molecular characteristics of 2 Japanese patients with adult-onset glutaric acidemia type II (GA2) were investigated and compared with those of pediatric cases.
  
  
  METHODS
  The patients were a 58-year-old male and a 31-year-old male. In both cases, episodes of myopathic symptoms, including myalgia, muscle weakness, and liver dysfunction of unknown cause, had been noted for the past several years. Muscle biopsy, urinary organic acid analysis (OA), acylcarnitine (AC) analysis in dried blood spots (DBS) and serum, immunoblotting, genetic analysis, and an in vitro probe acylcarnitine (IVP) assay were used for diagnosis and investigation.
  
  
  RESULTS
  In both cases, there was no obvious abnormality of AC in DBS or urinary OA, although there was a increase in medium- and long-chain ACs in serum; also, fat deposits were observed in the muscle biopsy. Immunoblotting and gene analysis revealed that both patients had GA2 due to a defect in electron transfer flavoprotein dehydrogenase (ETFDH). The IVP assay indicated no special abnormalities in either case.
  
  
  CONCLUSIONS
  Late-onset GA2 is separated into the intermediate and myopathic forms. In the myopathic form, episodic muscular symptoms or liver dysfunction are primarily exhibited after later childhood. Muscle biopsy and serum (or plasma) AC analysis allow accurate diagnosis in contrast with other biochemical tests, such as analysis of AC in DBS, urinary OA, or the IVP assay, which show fewer abnormalities in the myopathic form compared to intermediate form.
authors.affiliation: Department of Pediatrics, Shimane University Faculty of Medicine, Izumo, Shimane, Japan. Electronic address: k-yamada@med.shimane-u.ac.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Department of Pediatrics, Shimane University Faculty of Medicine, Izumo, Shimane, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Kobayashi
authors.affiliation: Department of Pediatrics, Shimane University Faculty of Medicine, Izumo, Shimane, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Bo
authors.affiliation: Department of Pediatrics, Shimane University Faculty of Medicine, Izumo, Shimane, Japan.
authors.forename: Tomoo
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Pediatrics, Shimane University Faculty of Medicine, Izumo, Shimane, Japan.
authors.forename: Jamiyan
authors.initials: J
authors.lastname: Purevsuren
authors.affiliation: Department of Pediatrics, Shimane University Faculty of Medicine, Izumo, Shimane, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hasegawa
authors.affiliation: Department of Pediatrics, Shimane University Faculty of Medicine, Izumo, Shimane, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Taketani
authors.affiliation: Department of Pediatrics, Shimane University Faculty of Medicine, Izumo, Shimane, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Fukuda
authors.affiliation: Department of Neurology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Ohkubo
authors.affiliation: Department of Neurology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Yokota
authors.affiliation: Department of Internal Medicine, Tokyo Metropolitan Bokutoh Hospital, Sumida-ku, Tokyo, Japan.
authors.forename: Mutsufusa
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Taiji
authors.initials: T
authors.lastname: Tsunemi
authors.affiliation: National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Mizusawa
authors.affiliation: Department of Neurology, University of Tsukuba Faculty of Medicine, Tsukuba, Ibaraki, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takuma
authors.affiliation: Department of Neurology, University of Tsukuba Faculty of Medicine, Tsukuba, Ibaraki, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Shioya
authors.affiliation: Department of Neurology, University of Tsukuba Faculty of Medicine, Tsukuba, Ibaraki, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Ishii
authors.affiliation: Department of Neurology, University of Tsukuba Faculty of Medicine, Tsukuba, Ibaraki, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Tamaoka
authors.affiliation: Department of Pediatrics, University of Fukui Faculty of Medical Sciences, Yoshida-gun, Fukui, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Shigematsu
authors.affiliation: Faculty of Health and Medical Sciences, Tokoha University, Hamamatsu, Shizuoka, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Sugie
authors.affiliation: Department of Pediatrics, Shimane University Faculty of Medicine, Izumo, Shimane, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Yamaguchi
mesh_terms: D000328:Adult; D000367:Age Factors; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood; D006801:Humans; D008297:Male; D054069:Multiple Acyl Coenzyme A Dehydrogenase Deficiency / Q000097:blood / Q000378:metabolism* / Q000473:pathology*; D018908:Muscle Weakness / Q000097:blood / Q000473:pathology; D009135:Muscular Diseases / Q000097:blood / Q000473:pathology
chemical_list: C116917:acylcarnitine; D002331:Carnitine
keywords: Adult onset; Immunoblotting; In vitro probe acylcarnitine assay; Multiple acyl-CoA dehydrogenase deficiency (glutaric acidemia type II); Myopathy; Serum acylcarnitine