-
Free Radical Biology & Medicine Nov 2015Mitochondria are a source of reactive oxygen species (ROS). Mitochondrial diseases are the result of inherited defects in mitochondrially expressed genes. One potential... (Review)
Review
Mitochondria are a source of reactive oxygen species (ROS). Mitochondrial diseases are the result of inherited defects in mitochondrially expressed genes. One potential pathomechanism for mitochondrial disease is oxidative stress. Oxidative stress can occur as the result of increased ROS production or decreased ROS protection. The role of oxidative stress in the five most common inherited mitochondrial diseases, Friedreich ataxia, LHON, MELAS, MERRF, and Leigh syndrome (LS), is discussed. Published reports of oxidative stress involvement in the pathomechanisms of these five mitochondrial diseases are reviewed. The strongest evidence for an oxidative stress pathomechanism among the five diseases was for Friedreich ataxia. In addition, a meta-analysis was carried out to provide an unbiased evaluation of the role of oxidative stress in the five diseases, by searching for "oxidative stress" citation count frequency for each disease. Of the five most common mitochondrial diseases, the strongest support for oxidative stress is for Friedreich ataxia (6.42%), followed by LHON (2.45%), MELAS (2.18%), MERRF (1.71%), and LS (1.03%). The increased frequency of oxidative stress citations was significant relative to the mean of the total pool of five diseases (p<0.01) and the mean of the four non-Friedreich diseases (p<0.0001). Thus there is support for oxidative stress in all five most common mitochondrial diseases, but the strongest, significant support is for Friedreich ataxia.
Topics: Humans; Mitochondrial Diseases; Oxidative Stress; Reactive Oxygen Species
PubMed: 26073122
DOI: 10.1016/j.freeradbiomed.2015.05.039 -
Pediatric Endocrinology, Diabetes, and... 2021With interest we read the article by Baszyńska-Wilk et al. about a 12 years old female who was diagnosed with mitochondrial encephalopathy, lactic acidosis, and...
With interest we read the article by Baszyńska-Wilk et al. about a 12 years old female who was diagnosed with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome upon the clinical presentation, blood tests, and the cerebral magnetic resonance imaging (MRI) [1]. The diagnosis was neither confirmed by biochemical nor by genetic investigations [1]. The study is appealing but raises the following concerns.
Topics: Acidosis, Lactic; Child; Female; Humans; Leigh Disease; MELAS Syndrome; Mitochondrial Encephalomyopathies; Stroke
PubMed: 35114773
DOI: 10.5114/pedm.2022.112695 -
American Journal of Ophthalmology Case... Jun 2023We present a unique case of foveomacular vitelliform lesions in a patient with metabolic encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS).
PURPOSE
We present a unique case of foveomacular vitelliform lesions in a patient with metabolic encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS).
OBSERVATIONS
After performing large panel next generation sequencing genetic testing, there was no likely alternative genetic etiology for vitelliform maculopathy in this patient.
CONCLUSIONS AND IMPORTANCE
We present a rare case of a visually asymptomatic pediatric patient with MELAS and vitelliform maculopathy, which may be part of the spectrum of retinal manifestations in MELAS. Pediatric-onset vitelliform maculopathy in MELAS may be under-diagnosed due to its asymptomatic nature. Given the known risk of choroidal neovascularization in vitelliform maculopathy, it is important to identify these patients for proper surveillance.
PubMed: 37096132
DOI: 10.1016/j.ajoc.2023.101842 -
Journal of Neurology Jun 2022Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a genetically heterogeneous disorder caused by mitochondrial DNA (mtDNA)... (Observational Study)
Observational Study
BACKGROUND
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a genetically heterogeneous disorder caused by mitochondrial DNA (mtDNA) mutations in the MT-TL1 gene. The pathophysiology of neurological manifestations is still unclear, but neuronal hyperexcitability and neuron-astrocyte uncoupling have been suggested. Glutamatergic neurotransmission is linked to glucose oxidation and mitochondrial metabolism in astrocytes and neurons. Given the relevance of neuron-astrocyte metabolic coupling and astrocyte function regulating energetic metabolism, we aimed to assess glutamate and glutamine CSF levels in MELAS patients.
METHODS
This prospective observational case-control study determined glutamate and glutamine CSF levels in patients with MELAS syndrome and compared them with controls. The plasma and CSF levels of the remaining amino acids and lactate were also determined.
RESULTS
Nine adult patients with MELAS syndrome (66.7% females mean age 35.8 ± 3.2 years) and 19 controls (63.2% females mean age 42.7 ± 3.8 years) were included. The CSF glutamate levels were significantly higher in patients with MELAS than in controls (18.48 ± 1.34 vs. 5.31 ± 1.09 μmol/L, p < 0.001). Significantly lower glutamine concentrations in patients with MELAS than controls were shown in CSF (336.31 ± 12.92 vs. 407.06 ± 15.74 μmol/L, p = 0.017). Moreover, the CSF levels of alanine, the branched-chain amino acids (BCAAs) and lactate were significantly higher in patients with MELAS.
CONCLUSIONS
Our results suggest the glutamate-glutamine cycle is altered probably due to metabolic imbalance, and as a result, the lactate-alanine and BCAA-glutamate cycles are upregulated. These findings might have therapeutic implications in MELAS syndrome.
Topics: Adult; Alanine; Case-Control Studies; DNA, Mitochondrial; Female; Glutamic Acid; Glutamine; Humans; Lactic Acid; MELAS Syndrome; Male; Middle Aged; Stroke
PubMed: 35088140
DOI: 10.1007/s00415-021-10942-7 -
Neurotherapeutics : the Journal of the... Apr 2013Mitochondrial diseases are a diverse group of inherited and acquired disorders that result in inadequate energy production. They can be caused by inheritable genetic... (Review)
Review
Mitochondrial diseases are a diverse group of inherited and acquired disorders that result in inadequate energy production. They can be caused by inheritable genetic mutations, acquired somatic mutations, and exposure to toxins (including some prescription medications). Normal mitochondrial physiology is responsible, in part, for the aging process itself, as free radical production within the mitochondria results in a lifetime burden of oxidative damage to DNA, especially the mitochondrial DNA that, in turn, replicate the mutational burden in future copies of itself, and lipid membranes. Primary mitochondrial diseases are those caused by mutations in genes that encode for mitochondrial structural and enzymatic proteins, and those proteins required for mitochondrial assembly and maintenance. A number of common adult maladies are associated with defective mitochondrial energy production and function, including diabetes, obesity, hyperthyroidism, hypothyroidism, and hyperlipidemia. Mitochondrial dysfunction has been demonstrated in many neurodegenerative disorders, including Alzheimer's disease, Parkinson disease, amyotrophic lateral sclerosis, and some cancers. Polymorphisms in mitochondrial DNA have been linked to disease susceptibility, including death from sepsis and survival after head injury. There is considerable overlap in symptoms caused by primary mitochondrial diseases and those illnesses that affect mitochondrial function, but are not caused by primary mutations, as well as disorders that mimic mitochondrial diseases, but are caused by other identified mutations. Evaluation of these disorders is complex, expensive, and not without false-negative and false-positive results that can mislead the physician. Most of the common heritable mitochondrial disorders have been well-described in the literature, but can be overlooked by many clinicians if they are uneducated about these disorders. In general, the evaluation of the classic mitochondrial disorders has become straightforward if the clinician recognized the phenotype and orders appropriate confirmatory testing. However, the majority of patients referred for a mitochondrial evaluation do not have a clear presentation that allows for rapid identification and testing. This article provides introductory comments on mitochondrial structure, physiology, and genetics, but will focus on the presentation and evaluation of adults with mitochondrial symptoms, but who may not have a primary mitochondrial disease.
Topics: Adult; Humans; MELAS Syndrome; MERRF Syndrome; Mitochondria; Mitochondrial Diseases; Nervous System Diseases; Precision Medicine; Terminology as Topic
PubMed: 23549648
DOI: 10.1007/s13311-013-0188-3 -
Biochimica Et Biophysica Acta Jul 2004By convention, the term "mitochondrial diseases" refers to disorders of the mitochondrial respiratory chain, which is the only metabolic pathway in the cell that is... (Review)
Review
By convention, the term "mitochondrial diseases" refers to disorders of the mitochondrial respiratory chain, which is the only metabolic pathway in the cell that is under the dual control of the mitochondrial genome (mtDNA) and the nuclear genome (nDNA). Therefore, a genetic classification of the mitochondrial diseases distinguishes disorders due to mutations in mtDNA, which are governed by the relatively lax rules of mitochondrial genetics, and disorders due to mutations in nDNA, which are governed by the stricter rules of mendelian genetics. Mutations in mtDNA can be divided into those that impair mitochondrial protein synthesis in toto and those that affect any one of the 13 respiratory chain subunits encoded by mtDNA. Essential clinical features for each group of diseases are reviewed. Disorders due to mutations in nDNA are more abundant not only because most respiratory chain subunits are nucleus-encoded but also because correct assembly and functioning of the respiratory chain require numerous steps, all of which are under the control of nDNA. These steps (and related diseases) include: (i) synthesis of assembly proteins; (ii) intergenomic signaling; (iii) mitochondrial importation of nDNA-encoded proteins; (iv) synthesis of inner mitochondrial membrane phospholipids; (v) mitochondrial motility and fission.
Topics: DNA, Mitochondrial; Electron Transport; Gene Rearrangement; Genome, Human; Humans; MELAS Syndrome; MERRF Syndrome; Mitochondrial Diseases; Mitochondrial Proteins; Mutation; Phenotype; Point Mutation; Retinitis Pigmentosa
PubMed: 15282178
DOI: 10.1016/j.bbabio.2004.03.014 -
American Journal of Ophthalmology Case... Jun 2024To describe examination and findings in a case of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) with particular focus on the ocular...
PURPOSE
To describe examination and findings in a case of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) with particular focus on the ocular sequelae from diabetes.
OBSERVATIONS
Neovascular glaucoma is not a common manifestation of MELAS.
CONCLUSIONS AND IMPORTANCE
We present a rare case of neovascular glaucoma in a patient with MELAS with a history of diabetes, hearing loss, and macular dystrophy. MELAS should be suspected in patients with this constellation of symptoms.
PubMed: 38707951
DOI: 10.1016/j.ajoc.2024.102064 -
Neurology India Jun 2002The mitochondrial cytopathies are genetically and phenotypically heterogeneous group of disorders caused by structural and functional abnormalities in mitochondria. To...
The mitochondrial cytopathies are genetically and phenotypically heterogeneous group of disorders caused by structural and functional abnormalities in mitochondria. To the best of our knowledge, there are very few studies published from India till date. Selected and confirmed fourteen cases of neurological mitochondrial cytopathies with different clinical syndromes admitted between 1997 and 2000 are being reported. There were 8 male and 6 female patients. The mean age was 24.42+/-11.18 years (range 4-40 years). Twelve patients could be categorized into well-defined syndromes, while two belonged to undefined group. In the defined syndrome categories, three patients had MELAS (mitochondrial encephalopathy, lactic acidosis and stroke like episodes), three had MERRF (myoclonic epilepsy and ragged red fibre myopathy), three cases had KSS (Kearns-Sayre Syndrome) and three were diagnosed to be suffering from mitochondrial myopathy. In the uncategorized group, one case presented with paroxysmal kinesogenic dystonia and the other manifested with generalized chorea alone. Serum lactic acid level was significantly increased in all the patients (fasting 28.96+/-4.59 mg%, post exercise 41.02+/-4.93 mg%). Muscle biopsy was done in all cases. Succinic dehydrogenase staining of muscle tissue showed subsarcolemmal accumulation of mitochondria in 12 cases. Mitochondrial DNA study could be performed in one case only and it did not reveal any mutation at nucleotides 3243 and 8344. MRI brain showed multiple infarcts in MELAS, hyperintensities in putaminal areas in chorea and bilateral cerebellar atrophy in MERRF.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; India; Kearns-Sayre Syndrome; MELAS Syndrome; MERRF Syndrome; Male; Mitochondrial Myopathies
PubMed: 12134180
DOI: No ID Found -
ENeurologicalSci Sep 2016This paper reported an unusual manifestation of a 19-year-old Chinese male patient presented with a complex phenotype of mitochondrial encephalomyopathy, lactic acidosis...
This paper reported an unusual manifestation of a 19-year-old Chinese male patient presented with a complex phenotype of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome and Kearns-Sayre syndrome (KSS). He was admitted to our hospital with the chief complaint of "acute fever, headache and slow reaction for 21 days". He was initially misdiagnosed as "viral encephalitis". This Chinese man with significant past medical history of intolerating fatigue presented paroxysmal neurobehavioral attacks that started about 10 years ago. During this span, 3 or 4 attack clusters were described during which several attacks occurred over a few days. The further examination found that the hallmark signs of this patient included progressive myoclonus epilepsy, cerebellar ataxia, hearing loss, myopathic weakness, ophthalmoparesis, pigmentary retinopathy and bifascicular heart block (Wolff-Parkinson-White syndrome). By young age the disease progression is characterized by the addition of migraine, vomiting, and stroke-like episodes, symptoms of MELAS expression, which indicated completion of the MELAS/KSS overlap syndrome. The m. A3243G mitochondrial DNA mutation and single large-scale mtDNA deletions were found in this patient. This mutation has been reported with MELAS, KSS, myopathy, deafness and mental disorder with cognitive impairment. This is the first description with a MELAS/KSS syndrome in Chinese.
PubMed: 29430542
DOI: 10.1016/j.ensci.2016.04.006 -
Acta Medica Portuguesa Jun 1994Mitochondrial Encephalomyopathies are primary disorders of energy metabolism recently described. They are the result of mitochondrial abnormalities with a wide spectrum... (Review)
Review
Mitochondrial Encephalomyopathies are primary disorders of energy metabolism recently described. They are the result of mitochondrial abnormalities with a wide spectrum of syndromes implying a multisystemic but predominantly muscular and cerebral involvement. Biochemical, histological, imagiologic and clinical features of the three well known mitochondrial syndromes (MERRF, MELAS and KSS) are described, as well as the mitochondrial genetics and maternal inheritance pattern.
Topics: Energy Metabolism; Humans; Mitochondria; Mitochondrial Encephalomyopathies; Syndrome
PubMed: 7942140
DOI: No ID Found