Mitochondrial impairment in patients and asymptomatic mutation carriers of Huntington's disease

• Published in: Movement disorders 2005-06, Vol.20 (6), p.674-679
• Main Authors: Saft, Carsten, Zange, Jochen, Andrich, Jürgen, Müller, Klaus, Lindenberg, Katrin, Landwehrmeyer, Bernhard, Vorgerd, Matthias, Kraus, Peter H., Przuntek, Horst, Schöls, Ludger
• Format: Article
• Language: English
• Subjects: 31-phosphorus magnetic resonance spectroscopy; Adenosine Triphosphate - metabolism; Adult; Biological and medical sciences; Case-Control Studies; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; energy metabolism; Energy Metabolism - physiology; Exercise - physiology; Female; Humans; Huntingtin Protein; Huntington Disease - diagnosis; Huntington Disease - genetics; Huntington Disease - physiopathology; Huntington's disease; Immunohistochemistry - methods; Magnetic Resonance Spectroscopy - methods; Male; Medical sciences; Middle Aged; Mitochondrial Diseases - diagnosis; Mitochondrial Diseases - etiology; Mitochondrial Diseases - genetics; mitochondrial impairment; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; muscle histology; Muscle, Skeletal - physiopathology; Mutation; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neurology; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Phosphocreatine - metabolism; Reaction Time - physiology
• ISSN: 0885-3185; 1531-8257
• DOI: 10.1002/mds.20373

Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion in the IT‐15 gene; however, it remains unknown how the mutation leads to selective neurodegeneration. Several lines of evidence suggest impaired mitochondrial function as a component of the neurodegenerative process in HD. We assessed energy metabolism in the skeletal muscle of 15 HD patients and 12 asymptomatic mutation carriers in vivo using 31P magnetic resonance spectroscopy. Phosphocreatine recovery after exercise is a direct measure of ATP synthesis and was slowed significantly in HD patients and mutation carriers in comparison to age‐ and gender‐matched healthy controls. We found that oxidative function is impaired to a similar extent in manifest HD patients and asymptomatic mutation carriers. Our findings suggest that mitochondrial dysfunction is an early and persistent component of the pathophysiology of HD. © 2004 Movement Disorder Society