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Heart Failure Reviews Mar 2021Maternally mitochondrial dysfunction includes a heterogeneous group of genetic disorders which leads to the impairment of the final common pathway of energy metabolism.... (Review)
Review
Maternally mitochondrial dysfunction includes a heterogeneous group of genetic disorders which leads to the impairment of the final common pathway of energy metabolism. Coronary heart disease and coronary venous disease are two important clinical manifestations of mitochondrial dysfunction due to abnormality in the setting of underlying pathways. Mitochondrial dysfunction can lead to cardiomyopathy, which is involved in the onset of acute cardiac and pulmonary failure. Mitochondrial diseases present other cardiac manifestations such as left ventricular noncompaction and cardiac conduction disease. Different clinical findings from mitochondrial dysfunction originate from different mtDNA mutations, and this variety of clinical symptoms poses a diagnostic challenge for cardiologists. Heart transplantation may be a good treatment, but it is not always possible, and other complications of the disease, such as mitochondrial encephalopathy, lactic acidosis, and stroke-like syndrome, should be considered. To diagnose and treat most mitochondrial disorders, careful cardiac, neurological, and molecular studies are needed. In this study, we looked at molecular genetics of MIDs and cardiac manifestations in patients with mitochondrial dysfunction.
Topics: Cardiomyopathies; Heart Diseases; Humans; Mitochondria; Mitochondrial Diseases; Mitochondrial Encephalomyopathies
PubMed: 32728985
DOI: 10.1007/s10741-020-10009-1 -
Indian Journal of Pathology &... May 2022Metabolic myopathies are a diverse group of genetic disorders that result in impaired energy production. They are individually rare and several have received the 'orphan... (Review)
Review
Metabolic myopathies are a diverse group of genetic disorders that result in impaired energy production. They are individually rare and several have received the 'orphan disorder' status. However, collectively they constitute a relatively common group of disorders that affect not only the skeletal muscle but also the heart, liver, and brain among others. Mitochondrial disorders, with a frequency of 1/8000 population, are the commonest cause of metabolic myopathies. Three main groups that cause metabolic myopathy are glycogen storage disorders (GSD), fatty acid oxidation defects (FAOD), and mitochondrial myopathies. Clinically, patients present with varied ages at onset and neuromuscular features. While newborns and infants typically present with hypotonia and multisystem involvement chiefly affecting the liver, heart, kidney, and brain, patients with onset later in life present with exercise intolerance with or without progressive muscle weakness and myoglobinuria. In general, GSDs result in high-intensity exercise intolerance while, FAODs, and mitochondrial myopathies predominantly manifest during endurance-type activity, fasting, or metabolically stressful conditions. Evaluation of these patients comprises a meticulous clinical examination and a battery of investigations which includes- exercise stress testing, metabolic and biochemical screening, electrophysiological studies, neuro-imaging, muscle biopsy, and molecular genetics. Accurate and early detection of metabolic myopathies allows timely counseling to prevent metabolic crises and helps in therapeutic interventions. This review summarizes the clinical features, diagnostic tests, pathological features, treatment and presents an algorithm to diagnose these three main groups of disorders.
Topics: Algorithms; Heart; Humans; Infant, Newborn; Metabolism, Inborn Errors; Mitochondrial Myopathies; Muscular Diseases
PubMed: 35562160
DOI: 10.4103/ijpm.ijpm_1088_21 -
International Journal of Molecular... Dec 2022Mitochondrial myopathies represent a heterogeneous group of diseases caused mainly by genetic mutations to proteins that are related to mitochondrial oxidative... (Review)
Review
Mitochondrial myopathies represent a heterogeneous group of diseases caused mainly by genetic mutations to proteins that are related to mitochondrial oxidative metabolism. Meanwhile, a similar etiopathogenetic mechanism (i.e., a deranged oxidative phosphorylation and a dramatic reduction of ATP synthesis) reveals that the evolution of these myopathies show significant differences. However, some physiological and pathophysiological aspects of mitochondria often reveal other potential molecular mechanisms that could have a significant pathogenetic role in the clinical evolution of these disorders, such as: i. a deranged ROS production both in term of signaling and in terms of damaging molecules; ii. the severe modifications of nicotinamide adenine dinucleotide (NAD)+/NADH, pyruvate/lactate, and α-ketoglutarate (α-KG)/2- hydroxyglutarate (2-HG) ratios. A better definition of the molecular mechanisms at the basis of their pathogenesis could improve not only the clinical approach in terms of diagnosis, prognosis, and therapy of these myopathies but also deepen the knowledge of mitochondrial medicine in general.
Topics: Humans; Mitochondria; Mitochondrial Myopathies; Cell Respiration; Oxidative Phosphorylation; NAD; Reactive Oxygen Species
PubMed: 36613565
DOI: 10.3390/ijms24010124 -
Handbook of Clinical Neurology 2023Stroke-like episode is a paroxysmal neurological manifestation which affects a specific group of patients with mitochondrial disease. Focal-onset seizures,... (Review)
Review
Stroke-like episode is a paroxysmal neurological manifestation which affects a specific group of patients with mitochondrial disease. Focal-onset seizures, encephalopathy, and visual disturbances are prominent findings associated with stroke-like episodes, with a predilection for the posterior cerebral cortex. The most common cause of stroke-like episodes is the m.3243A>G variant in MT-TL1 gene followed by recessive POLG variants. This chapter aims to review the definition of stroke-like episode and delineate the clinical phenomenology, neuroimaging and EEG findings typically seen in patients. In addition, several lines of evidence supporting neuronal hyper-excitability as the key mechanism of stroke-like episodes are discussed. The management of stroke-like episodes should focus on aggressive seizure management and treatment for concomitant complications such as intestinal pseudo-obstruction. There is no robust evidence to prove the efficacy of l-arginine for both acute and prophylactic settings. Progressive brain atrophy and dementia are the sequalae of recurrent stroke-like episode, and the underlying genotype in part predicts prognosis.
Topics: Humans; Adult; MELAS Syndrome; Stroke; Mitochondrial Diseases; Mitochondria; Brain; Seizures
PubMed: 36813321
DOI: 10.1016/B978-0-12-821751-1.00005-1 -
Journal of Binocular Vision and Ocular... 2022Myopathies are neuromuscular disorders of the skeletal muscles, in which the main symptom is muscle weakness due to muscle fiber dysfunction. Myopathies may be... (Review)
Review
BACKGROUND
Myopathies are neuromuscular disorders of the skeletal muscles, in which the main symptom is muscle weakness due to muscle fiber dysfunction. Myopathies may be classified into two main categories: inherited and acquired. Hereditary myopathies are a heterogeneous group of diseases that include congenital myopathies, mitochondrial myopathies, myotonic syndromes, muscular dystrophies, and other myopathies.
PURPOSE
The objective of this paper is to review the ophthalmological findings and genetic patterns of hereditary myopathies.
METHODS
This review is based on articles obtained by a relevant search of the PubMed database.
CONCLUSION
Ophthalmoplegia with or without ptosis and pupil sparing appeared to be the most frequent ophthalmological manifestation of myopathies. The identification of the main ophthalmological features can help in the diagnosis and treatment of these muscular diseases.
Topics: Humans; Muscle, Skeletal; Muscular Diseases; Paresis
PubMed: 35049410
DOI: No ID Found -
Muscle & Nerve Sep 2023Metabolic myopathies are a set of rare inborn errors of metabolism leading to disruption in energy production. Relevant to skeletal muscle, glycogen storage disease and...
Metabolic myopathies are a set of rare inborn errors of metabolism leading to disruption in energy production. Relevant to skeletal muscle, glycogen storage disease and fatty acid oxidation defects can lead to exercise intolerance, rhabdomyolysis, and weakness in children and adults, distinct from the severe forms that involve multiple-organ systems. These nonspecific, dynamic symptoms along with conditions that mimic metabolic myopathies can make diagnosis challenging. Clinicians can shorten the time to diagnosis by recognizing the typical clinical phenotypes and performing next generation sequencing. With improved access and affordability of molecular testing, clinicians need to be well-versed in resolving variants of uncertain significance relevant to metabolic myopathies. Once identified, patients can improve quality of life, safely engage in exercise, and reduce episodes of rhabdomyolysis by modifying diet and lifestyle habits.
Topics: Humans; Quality of Life; Muscular Diseases; Metabolism, Inborn Errors; Muscle, Skeletal; Rhabdomyolysis; Mitochondrial Myopathies
PubMed: 37226557
DOI: 10.1002/mus.27840 -
Antioxidants & Redox Signaling Aug 2022Reactive oxygen species (ROS) are highly reactive compounds that behave like a double-edged sword; they damage cellular structures and act as second messengers in... (Review)
Review
Reactive oxygen species (ROS) are highly reactive compounds that behave like a double-edged sword; they damage cellular structures and act as second messengers in signal transduction. Mitochondria and endoplasmic reticulum (ER) are interconnected organelles with a central role in ROS production, detoxification, and oxidative stress response. Skeletal muscle is the most abundant tissue in mammals and one of the most metabolically active ones and thus relies mainly on oxidative phosphorylation (OxPhos) to synthesize adenosine triphosphate. The impairment of OxPhos leads to myopathy and increased ROS production, thus affecting both redox poise and signaling. In addition, ROS enter the ER and trigger ER stress and its maladaptive response, which also lead to a myopathic phenotype with mitochondrial involvement. Here, we review the role of ROS signaling in myopathies due to either mitochondrial or ER dysfunction. Relevant advances have been evolving over the last 10 years on the intricate ROS-dependent pathways that act as modifiers of the disease course in several myopathies. To this end, pathways related to mitochondrial biogenesis, satellite cell differentiation, and ER stress have been studied extensively in myopathies. The analysis of the chemistry and the exact quantitation, as well as the localization of ROS, are still challenging due to the intrinsic labile nature of ROS and the technical limitations of their sensors. The mechanistic studies of the pathogenesis of mitochondrial and ER-related myopathies offer a unique possibility to discover novel ROS-dependent pathways. . 37, 301-323.
Topics: Animals; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Mammals; Muscular Diseases; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species; Signal Transduction
PubMed: 35081731
DOI: 10.1089/ars.2021.0266 -
Journal of Clinical Medicine Jan 2022Mitochondrial disorders are the most common inherited conditions, characterized by defects in oxidative phosphorylation and caused by mutations in nuclear or... (Review)
Review
Mitochondrial disorders are the most common inherited conditions, characterized by defects in oxidative phosphorylation and caused by mutations in nuclear or mitochondrial genes. Due to its high energy request, skeletal muscle is typically involved. According to the International Workshop of Experts in Mitochondrial Diseases held in Rome in 2016, the term Primary Mitochondrial Myopathy (PMM) should refer to those mitochondrial disorders affecting principally, but not exclusively, the skeletal muscle. The clinical presentation may include general isolated myopathy with muscle weakness, exercise intolerance, chronic ophthalmoplegia/ophthalmoparesis (cPEO) and eyelids ptosis, or multisystem conditions where there is a coexistence with extramuscular signs and symptoms. In recent years, new therapeutic targets have been identified leading to the launch of some promising clinical trials that have mainly focused on treating muscle symptoms and that require populations with defined genotype. Advantages in next-generation sequencing techniques have substantially improved diagnosis. So far, an increasing number of mutations have been identified as responsible for mitochondrial disorders. In this review, we focused on the principal molecular genetic alterations in PMM. Accordingly, we carried out a comprehensive review of the literature and briefly discussed the possible approaches which could guide the clinician to a genetic diagnosis.
PubMed: 35160083
DOI: 10.3390/jcm11030632 -
The European Journal of Neuroscience Jul 2022Mitochondria are an autonomous organelle that plays a crucial role in the metabolic aspects of a cell. Cortical spreading depression (CSD) and fluctuations in the... (Review)
Review
Mitochondria are an autonomous organelle that plays a crucial role in the metabolic aspects of a cell. Cortical spreading depression (CSD) and fluctuations in the cerebral blood flow have for long been mechanisms underlying migraine. It is a neurovascular disorder with a unilateral manifestation of disturbing, throbbing and pulsating head pain. Migraine affects 2.6% and 21.7% of the general population and is the major cause of partial disability in the age group 15-49. Higher mutation rates, imbalance in concentration of physiologically relevant molecules and oxidative stress biomarkers have been the main themes of discussion in determining the role of mitochondrial disability in migraine. The correlation of migraine with other disorders like hemiplegic migraine; mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes [MELAS]; tension-type headache (TTH); cyclic vomiting syndrome (CVS), ischaemic stroke; and hypertension has helped in the assessment of the physiological and morphogenetic basis of migraine. Here, we have reviewed the different nuances of mitochondrial dysfunction and migraine. The different mtDNA polymorphisms that can affect the generation and transmission of nerve impulse has been highlighted and supported with research findings. In addition to this, the genetic basis of migraine pathogenesis as a consequence of mutations in nuclear DNA that can, in turn, affect the synthesis of defective mitochondrial proteins is discussed along with a brief overview of epigenetic profile. This review gives an overview of the pathophysiology of migraine and explores mitochondrial dysfunction as a potential underlying mechanism. Also, therapeutic supplements for managing migraine have been discussed at different junctures in this paper.
Topics: Brain Ischemia; Humans; MELAS Syndrome; Migraine Disorders; Mitochondria; Mutation; Stroke
PubMed: 35478208
DOI: 10.1111/ejn.15676 -
Cell Calcium Mar 2021Mitochondrial activity warrants energy supply to oxidative myofibres to sustain endurance workload. The maintenance of mitochondrial homeostasis is ensured by the... (Review)
Review
Mitochondrial activity warrants energy supply to oxidative myofibres to sustain endurance workload. The maintenance of mitochondrial homeostasis is ensured by the control of fission and fusion processes and by the mitophagic removal of aberrant organelles. Many diseases are due to or characterized by dysfunctional mitochondria, and altered mitochondrial dynamics or turnover trigger myopathy per se. In this review, we will tackle the role of mitochondrial dynamics, turnover and metabolism in skeletal muscle, both in health and disease.
Topics: Animals; Health; Humans; Mitochondria, Muscle; Mitochondrial Dynamics; Mitophagy; Muscle, Skeletal; Muscular Diseases
PubMed: 33550207
DOI: 10.1016/j.ceca.2021.102357