Background Mitochondrial dysfunction is discussed as a key factor in pathogenesis of Huntington's Disease. 13C-methionine breath test has been established for non-invasive and easy to perform quantification of hepatic mitochondrial function.
Aim Aim of this pilot study was to investigate if there is evidence for subclinic hepatic mitochondrial dysfunction in manifest and/or premanifest Huntington's Disease mutation carriers using the 13C-methionine breath test.
Methods 13C-methionine breath test was performed within a group of 21 early manifest Huntington's Disease patients without medication, 30 premanifest mutation carriers as well as 36 healthy controls. All HD participants were scored according to the Unified Huntington's Disease Rating Scale, premanifest mutation carriers were stratified into the two 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. 13C-methionine breath test was performed after an overnight fasting, breath samples were analysed by non-dispersive isotope-selective infrared spectroscopy and results expressed as percentage dose recovered after 90 min of testing time. In 25 preHD participants a longtudinal follow-up investigation after 14.5 month was possible. Statistical analysis comprised ANCOVA and post hoc t-tests.
Results Manifest Huntington's Disease patients and mutation carriers from our PreHD-B group revealed a significant lower amount of exhaled 13CO2 compared to healthy controls (p<0.001; p=0.017 respectively). In a stepwise linear regression model breath test results correlate significant to functional and cognitive scores of the Unified Huntington's Disease Rating Scale in manifest and also in premanifest Huntington's Disease. For all mutation carriers together there was a weak, but significant correlation of breath test results to ratio caudate volume/total intracranial volume. PreHD-B (nearer) mutation cariers showed a significant lower amount of exhaled 13CO2 after 14.5 month.
Conclusions This study clearly demonstrates for the first time in vivo a subclinical, progredient hepatic involvement in manifest and premanifest Huntington's Disease.
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