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Clinical Biochemistry Feb 2023
Topics: Humans; MELAS Syndrome
PubMed: 36402172
DOI: 10.1016/j.clinbiochem.2022.11.007 -
Cureus Dec 2022Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a mitochondrial disease that lacks a definitive treatment. Lately, there has... (Review)
Review
Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a mitochondrial disease that lacks a definitive treatment. Lately, there has been an increased interest in the scientific community about the role of arginine in the short and long-term settings of the disease. We aim to conduct a systematic review of the clinical use of arginine in the management of MELAS and explore the role of arginine in the pathophysiology of the disease. We used PubMed advanced-strategy searches and only included full-text clinical trials on humans written in the English language. After applying the inclusion/exclusion criteria, four clinical trials were reviewed. We used the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol for this systematic review. We used the Cochrane Collaboration risk-of-bias tool to assess the bias encountered in each study. Overall, IV arginine seems to be effective in improving symptoms during acute attacks of MELAS, while oral arginine supplementation increases endothelial function, preventing further stroke-like episodes.
PubMed: 36686069
DOI: 10.7759/cureus.32709 -
Journal of Clinical Medicine Nov 2021Mitochondrial disorders are a remarkably complex group of diseases caused by impairment of the mitochondrial respiratory chain (or electron transport chain) [...].
Mitochondrial disorders are a remarkably complex group of diseases caused by impairment of the mitochondrial respiratory chain (or electron transport chain) [...].
PubMed: 34830516
DOI: 10.3390/jcm10225235 -
Molecular Genetics & Genomic Medicine Jul 2022Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome is one of the most well-known mitochondrial diseases, with most cases... (Review)
Review
BACKGROUND
Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome is one of the most well-known mitochondrial diseases, with most cases attributed to m.3243A>G. MELAS syndrome patients typically present in the first two decades of life with a broad, multi-systemic phenotype that predominantly features neurological manifestations--stroke-like episodes. However, marked phenotypic variability has been observed among paediatric patients, creating a clinical challenge and delaying diagnoses.
METHODS
A literature review of paediatric MELAS syndrome patients and a retrospective analysis in a UK tertiary paediatric neurology centre were performed.
RESULTS
Three children were included in this case series. All patients presented with seizures and had MRI changes not confined to a single vascular territory. Blood heteroplasmy varied considerably, and one patient required a muscle biopsy. Based on a literature review of 114 patients, the mean age of presentation is 8.1 years and seizures are the most prevalent manifestation of stroke-like episodes. Heteroplasmy is higher in a tissue other than blood in most cases.
CONCLUSION
The threshold for investigating MELAS syndrome in children with suspicious neurological symptoms should be low. If blood m.3243A>G analysis is negative, yet clinical suspicion remains high, invasive testing or further interrogation of the mitochondrial genome should be considered.
Topics: Acidosis, Lactic; Child; Humans; MELAS Syndrome; Retrospective Studies; Seizures; Stroke
PubMed: 35474314
DOI: 10.1002/mgg3.1955 -
Laryngoscope Investigative... Feb 2020Describe the histopathology of the temporal bones in MELAS (myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) syndrome. The syndrome results from a...
OBJECTIVES
Describe the histopathology of the temporal bones in MELAS (myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) syndrome. The syndrome results from a known point mutation in mitochondrial DNA.
METHODS
Histopathology analysis of a pair of temporal bones from the oldest surviving MELAS syndrome temporal bone donor. Histopathologic findings were correlated with known premortem clinical data.
RESULTS
The inner ears showed severe but incomplete atrophy of the stria vascularis for the length of the cochleae. In contrast, the organ of Corti and inner hair cells appeared intact with some loss of outer hair cells. Other than moderate loss at the basal turn, spiral ganglion cells numbers were normal. The vestibular neuroepithelium was mostly normal with the exception of moderate degeneration of the macula sacculi and partial collapse of the saccular wall on the right. The cerebral cortex had infarct-like lesions with adjacent gliosis.
CONCLUSION
This is an analysis of the oldest patient with MELAS syndrome to date, an addition to only two previously published patients. It supports the notion that hearing loss is a result of dysfunction of the stria vascularis and not loss of hair cells or neurons. Patterns of vestibular pathology are in agreement to in-vivo measurements. These findings support auditory rehabilitation with cochlear implants and may be relevant to hearing loss due to other mitochondrial mutations.
LEVEL OF EVIDENCE
4.
PubMed: 32128442
DOI: 10.1002/lio2.344 -
International Journal of Molecular... Mar 2024MELAS syndrome, characterized by mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes, represents a devastating mitochondrial disease, with... (Review)
Review
MELAS syndrome, characterized by mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes, represents a devastating mitochondrial disease, with the stroke-like episodes being its primary manifestation. Arginine supplementation has been used and recommended as a treatment for these acute attacks; however, insufficient evidence exists to support this treatment for MELAS. The mechanisms underlying the effect of arginine on MELAS pathophysiology remain unclear, although it is hypothesized that arginine could increase nitric oxide availability and, consequently, enhance blood supply to the brain. A more comprehensive understanding of these mechanisms is necessary to improve treatment strategies, such as dose and regimen adjustments; identify which patients could benefit the most; and establish potential markers for follow-up. This review aims to analyze the existing evidence concerning the mechanisms through which arginine supplementation impacts MELAS pathophysiology and provide the current scenario and perspectives for future investigations.
Topics: Humans; MELAS Syndrome; Acidosis, Lactic; Arginine; Stroke; Dietary Supplements
PubMed: 38612442
DOI: 10.3390/ijms25073629 -
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 -
European Journal of Endocrinology Nov 2020Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a very rare condition; it encompasses a diverse group of disorders...
OBJECTIVE
Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a very rare condition; it encompasses a diverse group of disorders including diabetes. Phenotypic variability can be attributed to heteroplasmy along with varying proportions of mutant and WT mitochondrial DNA (mtDNA). To examine the clinical relationship between mitochondrial diabetes and mutational load, we analyzed the mtDNA of children and young adolescents with MELAS syndrome using next generation sequencing (NGS).
DESIGN AND METHODS
Of 57 subjects with suspected MELAS syndrome, 32 children and young adolescents were diagnosed as MELAS syndrome with mtDNA A-to-G transition at nucleotide 3243. Mutation load studies and NGS were performed for 25 subjects.
RESULTS
The mean mutation load was 60.4 ± 18.4% (range: 22.5‒100). Of the 25 subjects with NGS results, 15 (60%) were diagnosed with DM and 2 (8%) were diagnosed with impaired glucose tolerance (IGT). The mutational load of subjects inversely correlated with first symptom onset, age at diagnosis of MELAS syndrome, and DM (P < 0.001). However, mutational load did not correlate with the clinical severity or progression of DM/IGT. There was no significant difference in insulin resistance or sensitivity indices between the low- and high-mutation load groups. During the 3.7 years of follow-up, insulin resistance indices were not significantly different between baseline and follow-up.
CONCLUSIONS
We can infer that the mutation load in the MELAS syndrome is significantly associated with the onset of symptoms and associated diseases, including mitochondrial diabetes. However, it may not influence disease progression.
Topics: Adolescent; Child; DNA, Mitochondrial; Diabetes Mellitus; Female; Glucose Intolerance; High-Throughput Nucleotide Sequencing; Humans; MELAS Syndrome; Male; Mitochondria; Mutation
PubMed: 33107434
DOI: 10.1530/EJE-20-0189 -
Journal of Neurology Feb 2024Mitochondrial myopathy without extraocular muscles involvement (MiMy) represents a distinct form of mitochondrial disorder predominantly affecting proximal/distal or...
OBJECTIVE
Mitochondrial myopathy without extraocular muscles involvement (MiMy) represents a distinct form of mitochondrial disorder predominantly affecting proximal/distal or axial muscles, with its phenotypic, genotypic features, and long-term prognosis poorly understood.
METHODS
A cross-sectional study conducted at a national diagnostic center for mitochondrial disease involved 47 MiMy patients, from a cohort of 643 mitochondrial disease cases followed up at Qilu Hospital from January 1, 2000, to January 1, 2021. We compared the clinical, pathological, and genetic features of MiMy to progressive external ophthalmoplegia (PEO) and mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) patients.
RESULTS
MiMy patients demonstrated a more pronounced muscle involvement syndrome, with lower 6MWT scores, higher FSS, and lower BMI compared to PEO and MELAS patients. Serum levels of creatinine kinase (CK), lactate, and growth and differentiation factor 15 (GDF15) were substantially elevated in MiMy patients. Nearly a third (31.9%) displayed signs of subclinical peripheral neuropathy, mostly axonal neuropathy. Muscle biopsies revealed that cytochrome c oxidase strong (COX-s) ragged-red fibers (RRFs) were a typical pathological feature in MiMy patients. Genetic analysis predominantly revealed mtDNA point pathogenic variants (59.6%) and less frequently single (12.8%) or multiple (4.2%) mtDNA deletions. During the follow-up, a majority (76.1%) of MiMy patients experienced stabilization or improvement after therapeutic intervention.
CONCLUSIONS
This study provides a comprehensive profile of MiMy through a large patient cohort, elucidating its unique clinical, genetic, and pathological features. These findings offer significant insights into the diagnostic and therapeutic management of MiMy, ultimately aiming to ameliorate patient outcomes and enhance the quality of life.
Topics: Humans; MELAS Syndrome; Oculomotor Muscles; Cross-Sectional Studies; Quality of Life; Stroke; DNA, Mitochondrial; Acidosis, Lactic; Ophthalmoplegia, Chronic Progressive External
PubMed: 37847292
DOI: 10.1007/s00415-023-12005-5 -
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