Cytochrome c oxidase Deficiency in Skeletal Muscle of Patients with Epilepsia Partialis Continua.
Abstract number :
2.041
Submission category :
Year :
2001
Submission ID :
2702
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
W.S. Kunz, PhD, Dept. Epileptology, University Bonn Medical Center, Bonn, Germany; A.P. Kudin, PhD, Dept. Epileptology, University Bonn Medical Center, Bonn, Germany; S. Vielhaber, MD, Dept. Neurology, University Magdeburg Medical Center, Magdeburg, Germa
RATIONALE: A putative causal role of mitochondria in some epilepsy syndromes is not well established. Until now only rather few patients with MERRF syndrome (myoclonus epilepsy with ragged red fibers) and one patient with Epilepsia partialis continua harbouring point mutations of mitochondrial tRNAs have been described.
METHODS: We determined mitochondrial function in skeletal muscle biopsy specimen of two unrelated 11- and 17-year old girls with medically intractable Epilepsia partialis continua applying analysis of mitochondrial enzyme activities and metabolic investigations of mitochondrial oxidative phosphorylation in saponin-permeabilized muscle fibers.
RESULTS: The histological evaluation of the muscle biopsy of both patients revealed substantially decreased staining with cytochrome c oxidase and slight accumulation of lipid in one patient. The typical ragged red fibers frequently observed in MERRF syndrome were absent. Quantitative determination of mitochondrial enzymes showed in comparison to controls an approximately two-fold decreased cytochrome c oxidase activity in the skeletal muscle homogenate while the activities of other mitochondrial enzymes (NADH:CoQ oxidoreductase; succinate:cytochrome c reductase and citrate synthase) were normal. Investigation of saponin-permeabilized muscle fibers indicated decreased respiration activities of fibers with the cytochrome c oxidase-specific substrate TMPD+ascorbate. Titrations of the respiration activity of saponin-permeabilized fibers with the specific inhibitor of cytochrome c oxidase cyanide revealed increased flux control coefficients and an about two-fold reduced metabolic threshold of cytochrome c oxidase in skeletal muscle of both patients.
CONCLUSIONS: Our findings strongly indicate an isolated cytochrome c oxidase deficiency as putative metabolic cause for the therapy resistant Epilepsia partialis continua in both described patients.
Support: This study was supported by the Deutsche Forschungsgemeinschaft (Ku 911/11).
Disclosure: Grant - Research grant by Deusche Forschungsgemeinschaft to W.S. Kunz.