Benign mitochondrial myopathy with decreased succinate cytochrome C reductase activity

Abstract

In most of the cases previously described, the defect on complex II was suggested by low activity of succinate cytochrome C reductase (SCCR). The clinical pattern of the previous 10 cases is heterogeneous and may be limited to one particular tissue or be of a more general nature. We report a 22‐year‐old‐woman, daughter of consanguineous parents, with generalized muscle weakness, easy fatigability and benign course, who showed a decrease of SCCR activity in mitochondria of muscle fibers. Free carnitine (FC) concentration was decreased in muscle as well. The muscle biopsy showed a mild variation in fiber size, with fiber type I predominance, subsarcolemmal oxidative DPNH accumulations, excess of neutral lipids and abnormally large mitochondria with paracrystalline inclusions. A possible inheritance pattern is discussed. Coenzyme Q10 therapy in this patient induced a significant increase of global MRC index score and a decrease of the turns‐mean amplitude ratio in the automatic analysis of the EMG.

Combined defects in oxidative phosphorylation and fatty acid β-oxidation in mitochondrial disease

“…Conversely, primary OXPHOS deficiencies can result in secondary FAO disease [129,130], highlighting the importance of the interactions between the FAO and OXPHOS pathways. Given the large range of metabolic diseases caused by OXPHOS and FAO deficiencies, a detailed understanding of the protein interactions between both pathways will be crucial for our comprehension of the pathogenesis involved and for the development of new therapies for the treatment of mitochondrial disease that will target both the FAO and OXPHOS pathways simultaneously.…”

“…Interestingly, primary disorders of one of these pathways have been shown to inhibit or disturb the other. These secondary defects are thought to arise from the build-up of toxic intermediates [54,121,123,[126][127][128][129][130][131]. However, there is growing evidence that physical links between FAO and OXPHOS proteins exist, raising the possibility that loss of these interactions may cause the secondary defects observed and therefore contribute to disease pathology [113,[128][129][130]132,133] The first descriptions of FAO-OXPHOS protein interactions were the identification of the FAO proteins, MTP and thiolase, bound to OXPHOS CI [132].…”

“…Primary OXPHOS CII deficiencies can result in metabolic disorders associated with secondary defects in FAO, presenting with cardiomyopathy, short stature, lactic acidosis, craniofacial dysmorphic features, hypertrichosis and myopathy [129,130]. Deficiencies in CII have been shown to inhibit FAO, resulting in toxic levels of butyrylcarnitine [129].…”

Alternative Sites for Proton Entry from the Cytoplasm to the Quinone Binding Site in Escherichia coli Succinate Dehydrogenase

“…This information is required for a detailed mechanism of enzyme catalysis and may even be crucial to understanding how certain disease states are manifested through mutations in complex II. Disease phenotypes associated with Sdh include Leigh syndrome , , Kearns−Sayre syndrome , and abnormal muscular development , , as well as familial pheochromocytoma and paraganglioma .…”