Kenji Yamada1, Hironori Kobayashi2, Ryosuke Bo2, Tomoo Takahashi2, Jamiyan Purevsuren2, Yuki Hasegawa2, Takeshi Taketani2, Seiji Fukuda2, Takuya Ohkubo3, Takanori Yokota3, Mutsufusa Watanabe4, Taiji Tsunemi5, Hidehiro Mizusawa6, Hiroshi Takuma7, Ayako Shioya7, Akiko Ishii7, Akira Tamaoka7, Yosuke Shigematsu8, Hideo Sugie9, Seiji Yamaguchi2. 1. Department of Pediatrics, Shimane University Faculty of Medicine, Izumo, Shimane, Japan. Electronic address: k-yamada@med.shimane-u.ac.jp. 2. Department of Pediatrics, Shimane University Faculty of Medicine, Izumo, Shimane, Japan. 3. Department of Neurology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan. 4. Department of Internal Medicine, Tokyo Metropolitan Bokutoh Hospital, Sumida-ku, Tokyo, Japan. 5. Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. 6. National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan. 7. Department of Neurology, University of Tsukuba Faculty of Medicine, Tsukuba, Ibaraki, Japan. 8. Department of Pediatrics, University of Fukui Faculty of Medical Sciences, Yoshida-gun, Fukui, Japan. 9. Faculty of Health and Medical Sciences, Tokoha University, Hamamatsu, Shizuoka, Japan.
Abstract
INTRODUCTION: 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. CONCLUSION: 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.
INTRODUCTION: 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. CONCLUSION: 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: Célia Nogueira; Lisbeth Silva; Ana Marcão; Carmen Sousa; Helena Fonseca; Hugo Rocha; Teresa Campos; Elisa Leão Teles; Esmeralda Rodrigues; Patrícia Janeiro; Ana Gaspar; Laura Vilarinho Journal: Biomedicines Date: 2021-05-04
Authors: Maria Anna Siano; Claudia Mandato; Lucia Nazzaro; Gennaro Iannicelli; Gian Paolo Ciccarelli; Ferdinando Barretta; Cristina Mazzaccara; Margherita Ruoppolo; Giulia Frisso; Carlo Baldi; Salvatore Tartaglione; Francesco Di Salle; Daniela Melis; Pietro Vajro Journal: Front Pediatr Date: 2021-05-10 Impact factor: 3.418