Mitochondria1 encephalomyopathy with decreased succinate‐cytochrome
            <i>c</i>
            reductase activity

Riggs, Jack E.; Schochet, Sydney S.; Fakadej, Alexander V.; Papadimitriou, A.; DiMauro, Salvatore; Crosby, Thomas W.; Gutmann, Ludwig; Moxley, Richard T.

doi:10.1212/wnl.34.1.48

Cited by 87 publications

(31 citation statements)

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“…Defects involving respiratory chain complexes I, III, and IV increasingly have been recognized as causes of muscle disease (29) but reports ofpatients with possible defects involving complex II (30,(31)(32)(33) or the TCA cycle (29) are rare. SDH deficiency has only recently been recognized (34)(35)(36) and aconitase deficiency has not previously been identified.…”

Section: Discussionmentioning

confidence: 99%

Deficiency of skeletal muscle succinate dehydrogenase and aconitase. Pathophysiology of exercise in a novel human muscle oxidative defect.

Haller¹,

Henriksson²,

Jorfeldt³

et al. 1991

J. Clin. Invest.

123

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We evaluated a 22-yr-old Swedish man with lifelong exercise intolerance marked by premature exertional muscle fatigue, dyspnea, and cardiac palpitations with superimposed episodes lasting days to weeks of increased muscle fatigability and weakness associated with painful muscle swelling and pigmenturia. Cycle exercise testing revealed low maximal oxygen uptake (12 ml/min per kg; healthy sedentary men = 39±5) with exaggerated increases in venous lactate and pyruvate in relation to oxygen uptake (V02) but low lactate/pyruvate ratios in maximal exercise. The severe oxidative limitation was characterized by impaired muscle oxygen extraction indicated by subnormal systemic arteriovenous oxygen difference (a-v 02 diff) in maximal exercise (patient = 4.0 ml/dl, normal men = 16.7±2.1) despite normal oxygen carrying capacity and Hgb-02 PSO. In contrast maximal oxygen delivery (cardiac output, Q) was high compared to sedentary healthy men (Q..: patient = 303 ml/min per kg, normal men 238±36) and the slope of increase in Q relative to V02 (i.e., A&Q/AVO2) from rest to exercise was exaggerated (A&Q/AVO2, patient = 29, normal men = 4.7±0.6) indicating uncoupling of the normal approximately 1:1 relationship between oxygen delivery and utilization in dynamic exercise. Studies of isolated skeletal muscle mitochondria in our patient revealed markedly impaired succinate oxidation with normal glutamate oxidation implying a metabolic defect at the level of complex II of the mitochondrial respiratory chain. A defect in Complex H in skeletal muscle was confirmed by the finding ofdeficiency ofsuccinate dehydrogenase as determined histochemically and biochemically. Immunoblot analysis showed low amounts of the 30-kD (iron-sulfur) and 13.5-kD proteins with near normal levels of the 70-kD protein of complex II. Deficiency of succinate dehydrogenase was associated with decreased levels of mitochondrial aconitase assessed enzymatically and immunologically whereas activities of other tricarboxylic acid cycle enzymes were increased compared to normal subjects. The exercise findings are consistent with the hypothesis that this defect impairs muscle oxidative metabolism by limiting the rate of NADH production by the tricarboxylic acid cycle. (J. Clin.

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Section: Discussionmentioning

confidence: 99%

Deficiency of skeletal muscle succinate dehydrogenase and aconitase. Pathophysiology of exercise in a novel human muscle oxidative defect.

Haller¹,

Henriksson²,

Jorfeldt³

et al. 1991

J. Clin. Invest.

123

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“…Complex I C20ORF7, FOXRED1, NDUFA1, NDUFA2, NDUFA7, NDUFA8 , NDUFA10, NDUFA11, NDUFA13, NDUFAF1, NDUFAF2, NDUFAF3, NDUFAF4 (HRPAP20), NDUFB6, NDUFS1, NDUFS2, NDUFS3, NDUFS4, NDUFS5, NDUFS6, NDUFS7, NDUFS8, NDUFV1, NDUFV3, NUBPL, ACAD9 [32][33][34]. Complex II deficiency due to SDHA mutations can cause Leigh syndrome, epilepsy, optic atrophy, ataxia, myopathy with exercise intolerance, cardiomyopathy, and leukoencephalopathy [32][33][34].…”

Section: Tablementioning

confidence: 99%

“…Complex II deficiency due to SDHA mutations can cause Leigh syndrome, epilepsy, optic atrophy, ataxia, myopathy with exercise intolerance, cardiomyopathy, and leukoencephalopathy [32][33][34]. SDHAF1 is the first complex II assembly factor reported to cause a leukoencephalopathy [35].…”

Section: Tablementioning

confidence: 99%

Mitochondrial Disease in Childhood: Nuclear Encoded

2013

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Primary mitochondrial disorders are clinically and genetically heterogeneous, caused by an alteration(s) in either mitochondrial DNA or nuclear DNA, and affect the respiratory chain's ability to undergo oxidative phosphorylation, leading to decreased production of adenosine triphosphophate and subsequent energy failure. These disorders may present at any age, but children tend to have an acute onset of disease compared with subacute or slowly progressive presentation in adults. Varying organ involvement also contributes to the phenotypic spectrum seen in these disorders. The childhood presentation of primary mitochondrial disease is mainly due to nuclear DNA mutations, with mitochondrial DNA mutations being less frequent in childhood and more prominent in adulthood disease. The clinician should be aware of the pediatric presentation of mitochondrial disease and have an understanding of the myriad of nuclear genes responsible for these disorders. The nuclear genes can be best understood by utilizing a classification system of location and function within the mitochondria.

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“…Magnetic resonance angiography may reveal occlusion of the distal internal carotid arteries with development of a collateral circulation (moyamoya disease) and stenosis of the intracerebral arteries 55 . Only in single cases, however, moyamoya has been described in patients with MCDs 34,56 .…”

Section: Cerebral Artery Stenoses and Moyamoya Diseasementioning

confidence: 99%

Central Nervous System Imaging in Mitochondrial Disorders

Finsterer

2009

Can. j. neurol. sci.

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Imaging of central-nervous-system (CNS) abnormalities is important in patients with mitochondrial disorders (MCDs) since the CNS is the organ second most frequently affected in MCDs and some of them are potentially treatable. Clinically relevant imaging techniques for visualization of CNS abnormalities in MCDs are computed tomography, magnetic resonance imaging, and MR-spectroscopy. The CNS abnormalities in MCDs visualized by imaging techniques include stroke-like lesions with cytotoxic or vasogenic edema, laminar cortical necrosis, basal ganglia necrosis, focal or diffuse white matter lesions, focal or diffuse atrophy, intra-cerebral calcifications, cysts, lacunas, hypometabolisation, lactacidosis, hemorrhages, cerebral hypo- or hyperperfusion, intra-cerebral artery stenoses, or moyamoya syndrome. The CNS lesions may proceed with or without clinical manifestations, why neuroimaging should be routinely carried out in all MCDs to assess the degree of CNS involvement. Some of these lesions may remain unchanged for years, some may show contiguous spread and progression, but some may even disappear, spontaneously or in response to medication. Dynamics of Stroke-like lesions may be positively influenced by L-arginine, dichloracetate, steroids, edavarone, or antiepileptics. Symptomatic treatment of CNS abnormalities in MCD patients may positively influence their outcome.

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Mitochondria1 encephalomyopathy with decreased succinate‐cytochrome c reductase activity

Cited by 87 publications

References 0 publications

Deficiency of skeletal muscle succinate dehydrogenase and aconitase. Pathophysiology of exercise in a novel human muscle oxidative defect.

Deficiency of skeletal muscle succinate dehydrogenase and aconitase. Pathophysiology of exercise in a novel human muscle oxidative defect.

Mitochondrial Disease in Childhood: Nuclear Encoded

Central Nervous System Imaging in Mitochondrial Disorders

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