A case of mitochondrial encephalomyopathy associated with a muscle coenzyme Q10 deficiency

Boitier, Eric; Degoul, Françoise; Desguerre, Isabelle; Charpentier, C.; François, Dominique; Ponsot, G; Diry, Monique; Rustin, Pierre; Marsac, Cécile

doi:10.1016/s0022-510x(98)00006-9

Cited by 122 publications

(78 citation statements)

References 23 publications

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“…This type of measurement may also identify mitochondrial defects that are not detectable with enzymatic analysis of the ETC on frozen samples [82,83]. Polarographic assay permits identification of coenzyme Q 10 synthetic defects when low oxygen utilization of both NADH and FADH-producing substrates is seen [84,85]. Functional studies may also detect abnormalities in PDHC deficiency, tricarboxylic acid cycle enzymes, beta-oxidation, coenzymes, complex V, and transmembrane carriers [51].…”

Section: Skeletal Muscle Analysismentioning

confidence: 99%

The in-depth evaluation of suspected mitochondrial disease

Haas

Parikh

Falk

et al. 2008

Molecular Genetics and Metabolism

313

300

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Mitochondrial disease confirmation and establishment of a specific molecular diagnosis requires extensive clinical and laboratory evaluation. Dual genome origins of mitochondrial disease, multiorgan system manifestations, and an ever increasing spectrum of recognized phenotypes represent the main diagnostic challenges. To overcome these obstacles, compiling information from a variety of diagnostic laboratory modalities can often provide sufficient evidence to establish an etiology. These include blood and tissue histochemical and analyte measurements, neuroimaging, provocative testing, enzymatic assays of tissue samples and cultured cells, as well as DNA analysis. As interpretation of results from these multifaceted investigations can become quite complex, the Diagnostic Committee of the Mitochondrial Medicine Society developed this review to provide an overview of currently available and emerging methodologies for the diagnosis of primary mitochondrial disease, primarily focusing on disorders characterized by impairment of oxidative phosphorylation. The aim of this work is to facilitate the diagnosis of mitochondrial disease by geneticists, neurologists, and other metabolic specialists who face the challenge of evaluating patients of all ages with suspected mitochondrial disease.

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Section: Skeletal Muscle Analysismentioning

confidence: 99%

The in-depth evaluation of suspected mitochondrial disease

Haas

Parikh

Falk

et al. 2008

Molecular Genetics and Metabolism

313

300

View full text Add to dashboard Cite

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“…Rotenone-sensitive Complex I (CI) activity, malonate-sensitive Complex II (CII) activity, antimycin A-sensitive Complex III (CIII) activity, KCN-sensitive Complex IV (CIV) activity, and oligomycin-sensitive Complex V (CV) activities were assayed as described [22,27,31]. CI-III and CII-III coupled assays were performed as described [25,[32][33][34].…”

Section: Enzyme Activitiesmentioning

confidence: 99%

“…Coenzyme Q (CoQ) levels play a basic role in enzyme function and coupling, and CoQ 9 is the predominant form in mouse tissues (Table 1) [33,34]. Since enzyme function and coupling activities differ significantly between pectoralis and quadriceps we measured their CoQ 9 levels in young, middle-aged, and aged mice, and used these values as a predictor of total CoQ for muscle mitochondria.…”

Section: Coenzyme Q Levels In Pectoralis and Quadriceps Mitochondriamentioning

confidence: 99%

Age-related alterations in oxidatively damaged proteins of mouse skeletal muscle mitochondrial electron transport chain complexes

Choksi

Nuss

DeFord

et al. 2008

Free Radical Biology and Medicine

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Age-associated mitochondrial dysfunction is a major source of reactive oxygen species (ROS) and oxidative modification to proteins. Mitochondrial electron transport chain (ETC) complexes I and III are the sites of ROS production and we hypothesize that proteins of the ETC complexes are primary targets of ROS-mediated modification which impairs their structure and function. The pectoralis, primarily an aerobic red muscle, and quadriceps, primarily an anaerobic white muscle, have different rates of respiration and oxygen-carrying capacity, and hence, different rates of ROS production. This raises the question of whether these muscles exhibit different levels of oxidative protein modification. Our studies reveal that the pectoralis shows a dramatic age-related decline in almost all complex activities that correlates with increased oxidative modification. Similar complex proteins were modified in the quadriceps, at a significantly lower level with less change in enzyme and ETC coupling function. We postulate that mitochondrial ROS causes damage to specific ETC subunits which increases with age and leads to further mitochondrial dysfunction. We conclude that physiological characteristics of the pectoralis vs quadriceps may play a role in age-associated rate of mitochondrial dysfunction and in the decline in tissue function.

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“…Primary CoQ 10 deficiency causes clinically heterogeneous diseases: 1) encephalomyopathy characterized by the triad of recurrent myoglobinuria, brain involvement and ragged-red fibers (Ogasahara et al, 1989;Sobreira et al, 1997;Boitier et al, 1998;DiGiovanni et al, 2001;Aure et al, 2004); 2) severe infantile multisystemic disease (Rötig et al, 2000;Rahman et al, 2001;Salviati et al, 2005); 3) cerebellar ataxia (Musumeci et al, 2001;Lamperti et al, 2003;Gironi et al, 2004;Artuch et al, 2006); 4) Leigh syndrome with growth retardation, ataxia and deafness (Van Mardergem et al, 2002); and 5) isolated myopathy (Lalani et al, 2005;Horvath et al, 2006). These disorders are transmitted as autosomal recessive traits and in most cases respond to CoQ 10 supplementation.…”

mentioning

confidence: 99%

“…For this reason, statin-related myopathy, manifesting as myalgia, muscle necrosis, and myoglobinura, has been hypothesized to be due to a partial deficiency of CoQ 10 (Folkers et al, 1985;Rundek et al 2004). Indirect support for this hypothesis comes from the first reported cases of CoQ 10 deficiency, which presented as exercise intolerance, recurrent myoglobinuria, and encephalopathy (mental retardation and seizures) (Ogashara et al, 1989;Sobreira et al, 1997;Boitier et al, 1998;Di Giovanni et al, 2001;Aure et al, 2004). Several groups have studied the effects of statins on the blood concentration of CoQ 10 in patients with hypercholesterolemia and healthy subjects and there are several reports showing that various statins partially decrease CoQ 10 levels in blood of patients with hypercholesterolemia and controls, although the number of subjects studied and the severity of CoQ 10 deficiency varied markedly (Folkers et al, 1985;Rundek et al, 2004).…”

mentioning

confidence: 99%