Mitochondrial myopathies in adults and children: management and therapy development

TY - JOUR

T1 - Mitochondrial myopathies in adults and children

T2 - management and therapy development

AU - Pitceathly, Robert D. S.

AU - McFarland, Robert

PY - 2014/10

Y1 - 2014/10

N2 - Purpose of reviewThe clinical and genetic heterogeneity of mitochondrial myopathies presents considerable diagnostic challenges. In addition, mitochondrial dysfunction seems to contribute to the development and progression of many age-related neurodegenerative diseases. This review presents recently published data concerning prevalence, phenotype, gene discovery, disease mechanisms, diagnostic tools and treatment strategies for mitochondrial diseases, and summarizes current understanding concerning the role mitochondria play in the pathogenesis of other common neurological disorders.Recent findingsHeteroplasmic levels of pathogenic mitochondrial DNA mutations are common amongst the general population, although there is considerable geographic variation. Mitochondrial abnormalities also occur in common neurodegenerative disorders, implying a mechanistic link between mitochondrial dysfunction and development or progression of disease. The phenotypic spectrum associated with well recognized pathogenic variants continues to expand, whereas next-generation sequencing is identifying new disease-causing nuclear genetic mutations. Biomarkers and imaging modalities for diagnosis and disease monitoring are now in place and novel treatment strategies are emerging. Alas, no clinical trial data for treatment in mitochondrial disease have been published in the last 12 months.SummaryDespite rapid advances in gene discovery, details concerning the altered protein products and cellular pathways that result in mitochondrial disease remain elusive. Understanding the consequences of deleterious mutations and the cellular adaptive response is imperative so that therapeutic targets can be identified.

AB - Purpose of reviewThe clinical and genetic heterogeneity of mitochondrial myopathies presents considerable diagnostic challenges. In addition, mitochondrial dysfunction seems to contribute to the development and progression of many age-related neurodegenerative diseases. This review presents recently published data concerning prevalence, phenotype, gene discovery, disease mechanisms, diagnostic tools and treatment strategies for mitochondrial diseases, and summarizes current understanding concerning the role mitochondria play in the pathogenesis of other common neurological disorders.Recent findingsHeteroplasmic levels of pathogenic mitochondrial DNA mutations are common amongst the general population, although there is considerable geographic variation. Mitochondrial abnormalities also occur in common neurodegenerative disorders, implying a mechanistic link between mitochondrial dysfunction and development or progression of disease. The phenotypic spectrum associated with well recognized pathogenic variants continues to expand, whereas next-generation sequencing is identifying new disease-causing nuclear genetic mutations. Biomarkers and imaging modalities for diagnosis and disease monitoring are now in place and novel treatment strategies are emerging. Alas, no clinical trial data for treatment in mitochondrial disease have been published in the last 12 months.SummaryDespite rapid advances in gene discovery, details concerning the altered protein products and cellular pathways that result in mitochondrial disease remain elusive. Understanding the consequences of deleterious mutations and the cellular adaptive response is imperative so that therapeutic targets can be identified.

KW - biomarkers

KW - genotype or phenotype

KW - mitochondrial disease

KW - neurodegeneration

KW - treatment

KW - GROWTH-FACTOR 21

KW - POINT MUTATIONS

KW - MERRF MUTATION

KW - DNA DELETIONS

KW - DISEASE

KW - PREVALENCE

KW - POPULATION

KW - A3243G

KW - EPIDEMIOLOGY

KW - DYSFUNCTION

U2 - 10.1097/WCO.0000000000000126

DO - 10.1097/WCO.0000000000000126

M3 - Literature review

SN - 1350-7540

VL - 27

SP - 576

EP - 582

JO - Current Opinion in Neurology

JF - Current Opinion in Neurology

IS - 5

ER -