title: Hepatic mitochondrial dysfunction in manifest and premanifest Huntington disease.
abstract: OBJECTIVE
  In this cross-sectional study, we investigated whether there is evidence for hepatic mitochondrial dysfunction in manifest and/or premanifest Huntington disease (HD) by using the ¹³C-methionine breath test.
  
  
  METHODS
  The ¹³C-methionine breath test was performed within a group of 21 patients with early manifest HD without medication, 30 premanifest mutation carriers, as well as 36 healthy controls. Premanifest mutation carriers were stratified into the 2 groups preHD-A (further from predicted onset) and preHD-B (nearer) based on a calculation of the probability of estimated disease onset within 5 years. The ¹³C-methionine breath test was performed after an overnight fasting, breath samples were analyzed by nondispersive isotope-selective infrared spectroscopy, and results expressed as percentage dose recovered after 90 minutes of testing time. Statistical analyses comprised analysis of covariance and post hoc t tests.
  
  
  RESULTS
  Patients with manifest HD and mutation carriers from our preHD-B group revealed a lower amount of exhaled ¹³CO₂ compared with healthy controls (p < 0.001 and p = 0.017, respectively). In a stepwise linear regression model, breath test results correlate to functional and cognitive scores of the Unified Huntington's Disease Rating Scale in manifest and also in premanifest HD. For all mutation carriers together, there was a weak but significant correlation of breath test results to ratio caudate volume/total intracranial volume.
  
  
  CONCLUSIONS
  This study demonstrates for the first time in vivo a subclinical, hepatic involvement in manifest and premanifest HD.
authors: Department of Neurology, Huntington Centre NRW, Ruhr-University Bochum, Bochum, Germany.
authors: Sven H
authors: SH
authors: Stüwe
authors: Oliver
authors: O
authors: Goetze
authors: Carsten
authors: C
authors: Lukas
authors: Peter
authors: P
authors: Klotz
authors: Rainer
authors: R
authors: Hoffmann
authors: Matthias
authors: M
authors: Banasch
authors: Michael
authors: M
authors: Orth
authors: Wolfgang E
authors: WE
authors: Schmidt
authors: Ralf
authors: R
authors: Gold
authors: Carsten
authors: C
authors: Saft
mesh_terms: D000328:Adult; D001944:Breath Tests; D002250:Carbon Radioisotopes; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000150:complications*; D008107:Liver Diseases / Q000175:diagnosis / Q000209:etiology*; D008297:Male; D008715:Methionine; D008875:Middle Aged; D008928:Mitochondria / Q000473:pathology; D019275:Radiopharmaceuticals; D055815:Young Adult
chemical_list: D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D008715:Methionine