Diagnosis and treatment of mitochondrial myopathies

Pfeffer, Gerald; Chinnery, Patrick F.

doi:10.3109/07853890.2011.605389

Cited by 129 publications

(118 citation statements)

References 98 publications

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“…Symptoms often involve the central nervous and cardiovascular systems. Kearns-Sayre syndrome, for example, is defined by the classical triad of age of onset before 20, extraocular muscle weakness, and pigmentary retinopathy, plus one of the following: ataxia, protein level greater than 100 mg/dL in cerebrospinal fluid, or cardiac conduction abnormalities [10]. Mitochondrial disease can be investigated either molecularly by gene panel or whole-exome sequencing, or by pathologic findings on muscle biopsy of abnormal respiratory chain function or the presence of ragged red fibers.…”

Section: Discussionmentioning

confidence: 99%

McArdle disease: a “pediatric” disorder presenting in an adult with acute kidney injury

Zhao

Soni

et al. 2017

CEN Case Rep

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Rhabdomyolysis is characterized by the acute breakdown of skeletal muscle, resulting in the release of muscle cell contents, subsequent myoglobinuria, and in severe cases, acute renal failure. A number of etiologies have been identified in acute rhabdomyolysis, in which drugs and trauma account for the majority of cases. One etiological category that is commonly overlooked in the adult population is an underlying genetic defect. This may be challenging to diagnose due to its rarity in the adult demographic and the marked heterogeneity, often requiring a high level of clinical suspicion before investigation is pursued. Once diagnosed, however, appropriate steps can be taken to reduce future episodes of rhabdomyolysis, further renal injury, and other systemic complications. Here, we report a case of an adult patient presenting with acute rhabdomyolysis secondary to McArdle disease, a genetic disease causing defective glycogenolysis. The case highlights the importance of recognizing the potential of undiagnosed ''pediatric'' disorders in adulthood and particularly for underlying genetic causes of rhabdomyolysis.

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Section: Discussionmentioning

confidence: 99%

McArdle disease: a “pediatric” disorder presenting in an adult with acute kidney injury

Zhao

Soni

et al. 2017

CEN Case Rep

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“…Dysfunction is most likely to occur in tissues/ organs with high energy requirements, therefore explaining that MM most often affects muscles (particularly extraocular muscle), and the nervous, cardiac, and endocrine systems. A detailed description of all mitochondrial myopathies, and their clinical characteristics, prognosis, diagnosis, and treatment is beyond the scope of this review, although this topic was recently reviewed in detail [26]. Clinically apparent respiratory dysfunction in mitochondrial myopathies appears to be an unusual finding: in recent series, respiratory dysfunction has similar prevalence to controls in patients with the m.3243A[G mutation [27], and was present in only one of 40 patients in a recent PEO series [28].…”

Section: Metabolic Myopathiesmentioning

confidence: 99%

Diagnosis of muscle diseases presenting with early respiratory failure

et al. 2014

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Here we describe a clinical approach and differential diagnosis for chronic muscle diseases which include early respiratory failure as a prominent feature in their presentation (i.e. respiratory failure whilst still ambulant). These patients typically present to neurology or respiratory medicine out-patient clinics and a distinct differential diagnosis of neuromuscular aetiologies should be considered. Amyotrophic lateral sclerosis and myasthenia gravis are the important non-muscle diseases to consider, but once these have been excluded there remains a challenging differential diagnosis of muscle conditions, which will be the focus of this review. The key points in the diagnosis of these disorders are being aware of relevant symptoms, which are initially caused by nocturnal hypoventilation or diaphragmatic weakness; and identifying other features which direct further investigation. Important muscle diseases to identify, because their diagnosis has disease-specific management implications, include adult-onset Pompe disease, inflammatory myopathy, and sporadic adult-onset nemaline myopathy. Cases which are due to metabolic myopathy or muscular dystrophy are important to diagnose because of their implications for genetic counselling. Myopathy from sarcoidosis and colchicine each has a single reported case with this presentation, but should be considered because they are treatable. Disorders which have recently had their genetic aetiologies identified include hereditary myopathy with early respiratory failure (due to TTN mutations), the FHL1-related syndromes, and myofibrillar myopathy due to BAG3 mutation. Recently described syndromes include oculopharyngodistal muscular dystrophy that awaits genetic characterisation.

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“…Inborn OXPHOS complex deficiencies caused by mutations in mitochondrial or nuclear DNA (mtDNA and nDNA, respectively), can lead to various diseases, concerning mostly tissues with high relative energy demand (in relation to OXPHOS capacity), such as skeletal muscle or neural tissue [40,5,13,35,36,39,34]. They are characterized by a threshold value of an OXPHOS complex/whole OXPHOS activity below which the disease develops.…”

Section: Introductionmentioning

confidence: 99%

Effects of OXPHOS complex deficiencies and ESA dysfunction in working intact skeletal muscle: implications for mitochondrial myopathies

Korzeniewski

2015

Biochimica et Biophysica Acta (BBA) - Bioenergetics

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The effects of inborn oxidative phosphorylation (OXPHOS) complex deficiencies or possible each-step activation (ESA) dysfunction on the bioenergetic system in working intact skeletal muscle are studied using a computer model of OXPHOS published previously. The curves representing the dependencies of V˙O2 and metabolite concentrations on single complex activity, entire OXPHOS activity or ESA intensity exhibit a characteristic threshold at some OXPHOS complex activity/ESA intensity. This threshold for V˙O2 of single complex activities is significantly lower in intact muscle during moderate and heavy work, than in isolated mitochondria in state 3. Metabolite concentrations and pH in working muscle start to change significantly at much higher OXPHOS complex activities/ESA intensities than V˙O2. The effect of entire OXPHOS deficiency or ESA dysfunction is potentially much stronger than the effect of a single complex deficiency. Implications of these findings for the genesis of mitochondrial myopathies are discussed. It is concluded that V˙O2 in state 3 and its dependence on complex activity in isolated mitochondria is not a universal quantitative determinant of the effect of mitochondrial dysfunctions in vivo. Moderate and severe mitochondria dysfunctions are defined: the former affect significantly only metabolite concentrations and pH, while the latter also decrease significantly V˙O2 in intact skeletal muscle during work. The dysfunction-caused decrease in V˙O2/oxidative ATP synthesis flux, disturbance of metabolite homeostasis, elevated ROS production and anaerobic glycolysis recruitment can account for such mitochondrial myopathy symptoms as muscle weakness, exercise intolerance (exertional fatigue) and lactic acidosis.

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Diagnosis and treatment of mitochondrial myopathies

Cited by 129 publications

References 98 publications

McArdle disease: a “pediatric” disorder presenting in an adult with acute kidney injury

McArdle disease: a “pediatric” disorder presenting in an adult with acute kidney injury

Diagnosis of muscle diseases presenting with early respiratory failure

Effects of OXPHOS complex deficiencies and ESA dysfunction in working intact skeletal muscle: implications for mitochondrial myopathies

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