Recurrent myoglobinuria due to a nonsense mutation in the COX I gene of mitochondrial DNA

Karadimas, Charalampos; Greenstein, Patricia E.; Sue, Carolyn M.; Joseph, Jasmin; Tanji, Kurenai; Haller, Ronald G.; Taivassalo, Tanja; Davidson, Mercy M.; Shanske, Sara; Bonilla, Eduardo; DiMauro, Salvatore

doi:10.1212/wnl.55.5.644

Cited by 101 publications

(49 citation statements)

References 28 publications

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“…Another emerging class of disorders that may manifest with recurrent myoglobinuria is the mitochondrial cytopathies. 4,5,28,70,74,101,113,115,147 Mitochondrial mutations linked to rhabdomyolysis are summarized in Table 4. In many cases, additional clinical features, such as progressive external ophthalmoplegia, are evident.…”

Section: Inherited Metabolic Myopathiesmentioning

confidence: 99%

Rhabdomyolysis: A review

2002

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Rhabdomyolysis, a syndrome of skeletal muscle breakdown with leakage of muscle contents, is frequently accompanied by myoglobinuria, and if sufficiently severe, acute renal failure with potentially life-threatening metabolic derangements may ensue. A diverse spectrum of inherited and acquired disorders affecting muscle membranes, membrane ion channels, and muscle energy supply causes rhabdomyolysis. Common final pathophysiological mechanisms among these causes of rhabdomyolysis include an uncontrolled rise in free intracellular calcium and activation of calcium-dependent proteases, which lead to destruction of myofibrils and lysosomal digestion of muscle fiber contents. Recent advances in molecular genetics and muscle enzyme histochemistry may enable a specific metabolic diagnosis in many patients with idiopathic recurrent rhabdomyolysis.

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Section: Inherited Metabolic Myopathiesmentioning

confidence: 99%

Rhabdomyolysis: A review

2002

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“…Inflammation is absent, and necrosis and regeneration are not seen, except in mitochondrial myopathies presenting with rhabdomyolysis. Rhabdomyolysis has been associated with mutations in CoQ2, mtDNA encoded CIV subunit genes (MT-CO1, MT-CO2, MT-CO3), and tRNA genes (MTT1, MT-TL1 m.3243 A > G MELAS mutation) [96][97][98][99][100][101][102][103][104][105][106][107] . Even late in the disease course, overtly dystrophic features with necrosis, fibrosis and fatty infiltration are not seen, with the exception of TK2-related myopathic form of mtDNA depletion syndrome 108,109 .…”

Section: Associated Pathological Featuresmentioning

confidence: 99%

Pathology of Adult and Paediatric Mitochondrial Myopathies

Phadke¹

2017

Preprint

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Mitochondria are dynamic organelles ubiquitously present in nucleated eukaryotic cells, subserving multiple metabolic functions, including cellular ATP generation by oxidative phosphorylation (OXPHOS). The OXPHOS machinery comprises five transmembrane respiratory chain enzyme complexes (RC). Defective OXPHOS gives rise to mitochondrial diseases (mtD). The incredible phenotypic and genetic diversity of mtD can be attributed at least in part to the RC dual genetic control (nuclear DNA [nDNA] and mitochondrial DNA [mtDNA]) and the complex interaction between the two genomes. Despite the increasing use of next-generation-sequencing (NGS) and various -omics platforms in unraveling novel mtD genes and pathomechanisms, current clinical practice for investigating mtD essentially involves a multipronged approach including clinical assessment, metabolic screening, imaging, pathological, biochemical and functional testing to guide molecular genetic analysis. This review addresses the broad muscle pathology landscape including genotype-phenotype correlations in adult and paediatric mtD, the role of immunodiagnostics in understanding some of the pathomechanisms underpinning the canonical features of mtD, and recent diagnostic advances in the field.

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“…84 In support of this, in one patient carrying a nonsense mutation in the COX I gene, recurrent myoglobinuria led to a positive selection of COX positive fibers harboring no mutant mtDNA. 83 …”

Section: Inducing Muscle Regenerationmentioning

confidence: 99%

How Can We Treat Mitochondrial Encephalomyopathies? Approaches to Therapy

2008

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Summary:Mitochondrial disorders are a heterogeneous group of diseases affecting different organs (brain, muscle, liver, and heart), and the severity of the disease is highly variable. The chronicity and heterogeneity, both clinically and genetically, means that many patients require surveillance follow-up over their lifetime, often involving multiple disciplines. Although our understanding of the genetic defects and their pathological impact underlying mitochondrial diseases has increased over the past decade, this has not been paralleled with regards to treatment. Currently, no definitive pharmacological treatment exists for patients with mitochondrial dysfunction, except for patients with primary deficiency of coenzyme Q10. Pharmacological and nonpharmacological treatments increasingly being investigated include ketogenic diet, exercise, and gene therapy. Management is aimed primarily at minimizing disability, preventing complications, and providing prognostic information and genetic counseling based on current best practice. Here, we evaluate therapies used previously and review current and future treatment modalities for both adults and children with mitochondrial disease.

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Recurrent myoglobinuria due to a nonsense mutation in the COX I gene of mitochondrial DNA

Cited by 101 publications

References 28 publications

Rhabdomyolysis: A review

Rhabdomyolysis: A review

Pathology of Adult and Paediatric Mitochondrial Myopathies

How Can We Treat Mitochondrial Encephalomyopathies? Approaches to Therapy

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