title: Abnormal in vivo skeletal muscle energy metabolism in Huntington's disease and dentatorubropallidoluysian atrophy.
abstract: We studied in vivo muscle energy metabolism in patients with Huntington's disease (HD) and dentatorubropallidoluysian atrophy (DRPLA) using 31P magnetic resonance spectroscopy (MRS). Twelve gene-positive HP patients (4 presymptomatic patients) and 2 gene-positive DRPLA patients (1 presymptomatic patient) were studied. 31P-MRS at rest showed a reduced phosphocreatine-to-inorganic phosphate ratio in the symptomatic HD patients and DRPLA patient. Muscle adenosine triphosphate/(phosphocreatine + inorganic phosphate) at rest was significantly reduced in both groups of symptomatic and presymptomatic HD subjects and was below the normal range in the 2 DRPLA subjects. During recovery from exercise, the maximum rate of mitochondrial adenosine triphosphate production was reduced by 44% in symptomatic HD patients and by 35% in presymptomatic HD carriers. The maximum rate of mitochondrial adenosine triphosphate production in muscle was also reduced by around 46% in the 2 DRPLA subjects. Our findings show that HD and DRPLA share a deficit of in vivo mitochondrial oxidative metabolism, supporting a role for mitochondrial dysfunction as a factor involved in the pathogenesis of these polyglutamine repeat-mediated neurodegenerative disorders. The identification of 31P-MRS abnormalities may offer a surrogate biochemical marker by which to study disease progression and the effects of treatment in HD and DRPLA.
authors.affiliation: Department of Biochemistry, University of Oxford, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Lodi
authors.forename: A H
authors.initials: AH
authors.lastname: Schapira
authors.forename: D
authors.initials: D
authors.lastname: Manners
authors.forename: P
authors.initials: P
authors.lastname: Styles
authors.forename: N W
authors.initials: NW
authors.lastname: Wood
authors.forename: D J
authors.initials: DJ
authors.lastname: Taylor
authors.forename: T T
authors.initials: TT
authors.lastname: Warner
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D001921:Brain / Q000378:metabolism; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D020191:Myoclonic Epilepsies, Progressive / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D010710:Phosphates; D010725:Phosphocreatine; C025403:phosphocreatinine; D000255:Adenosine Triphosphate