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Metabolites Sep 2022Stroke-like episodes (SLEs) are significant clinical manifestations of metabolic disorders affecting the central nervous system. Morphological equivalents presented in... (Review)
Review
Stroke-like episodes (SLEs) are significant clinical manifestations of metabolic disorders affecting the central nervous system. Morphological equivalents presented in neuroimaging procedures are described as stroke-like lesions (SLLs). It is crucial to distinguish SLEs from cerebral infarction or intracerebral hemorrhage, mainly due to the variety in management. Another significant issue to underline is the meaning of the main pathogenetic hypotheses in the development of SLEs. The diagnostic process is based on the patient's medical history, physical and neurological examination, neuroimaging techniques and laboratory and genetic testing. Implementation of treatment is generally symptomatic and includes L-arginine supplementation and adequate antiepileptic management. The main aim of the current review was to summarize the basic and actual knowledge about the occurrence of SLEs in various inherited neurometabolic disorders, discuss the possible pathomechanism of their development, underline the role of neuroimaging in the detection of SLLs and identification of the electroencephalographic patterns as well as histological abnormalities in inherited disorders of metabolism.
PubMed: 36295831
DOI: 10.3390/metabo12100929 -
Medicine Oct 2022The pathogenesis of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke like episodes (MELAS) syndrome has not been fully elucidated. The m.3243A > G...
The pathogenesis of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke like episodes (MELAS) syndrome has not been fully elucidated. The m.3243A > G mutation which is responsible for 80% MELAS patients affects proteins with undetermined functions. Therefore, we performed quantitative proteomic analysis on skeletal muscle specimens from MELAS patients. We recruited 10 patients with definitive MELAS and 10 age- and gender- matched controls. Proteomic analysis based on nanospray liquid chromatography-mass spectrometry (LC-MS) was performed using data-independent acquisition (DIA) method and differentially expressed proteins were revealed by bioinformatics analysis. We identified 128 differential proteins between MELAS and controls, including 68 down-regulated proteins and 60 up-regulated proteins. The differential proteins involved in oxidative stress were identified, including heat shock protein beta-1 (HSPB1), alpha-crystallin B chain (CRYAB), heme oxygenase 1 (HMOX1), glucose-6-phosphate dehydrogenase (G6PD) and selenoprotein P. Gene ontology and kyoto encyclopedia of genes and genomes pathway analysis showed significant enrichment in phagosome, ribosome and peroxisome proliferator-activated receptors (PPAR) signaling pathway. The imbalance between oxidative stress and antioxidant defense, the activation of autophagosomes, and the abnormal metabolism of mitochondrial ribosome proteins (MRPs) might play an important role in m.3243A > G MELAS. The combination of proteomic and bioinformatics analysis could contribute potential molecular networks to the pathogenesis of MELAS in a comprehensive manner.
Topics: Acidosis, Lactic; Antioxidants; DNA, Mitochondrial; Glucosephosphate Dehydrogenase; HSP27 Heat-Shock Proteins; Heme Oxygenase-1; Humans; MELAS Syndrome; Muscular Diseases; Mutation; Peroxisome Proliferator-Activated Receptors; Proteomics; Selenoprotein P; Stroke; alpha-Crystallin B Chain
PubMed: 36254078
DOI: 10.1097/MD.0000000000030938 -
Journal of the Belgian Society of... 2022Microhemorrhages have not been described in mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes syndrome (MELAS) on magnetic resonance imaging...
INTRODUCTION
Microhemorrhages have not been described in mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes syndrome (MELAS) on magnetic resonance imaging (MRI). Main symptoms and/or important findings: A MELAS-patient had a rapid succession of 3 stroke-like episodes with dysphasia, visual field deficits and paresis of the right arm. MRI showed a lesion with corticosubcortical vasogenic edema without reduced diffusion, conforming to a stroke-like MELAS-lesion. Microhemorrhages within MELAS-lesions were detected on MRI. The main diagnoses, therapeutic interventions, and outcomes: Microhemorrhages are an atypical imaging finding in MELAS. The patient was treated with L-arginine.
CONCLUSION
Microhemorrhages can present on MRI in (sub)acute MELAS lesions and may reflect mitochondrial microangiopathy.
PubMed: 36248725
DOI: 10.5334/jbsr.2891 -
Journal of Medical Case Reports Oct 2022Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode syndrome is a rare mitochondrial genetic disorder that can present with a variety of clinical...
Delay in diagnosing a patient with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome who presented with status epilepticus and lactic acidosis: a case report.
BACKGROUND
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode syndrome is a rare mitochondrial genetic disorder that can present with a variety of clinical manifestations, including stroke, hearing loss, seizures, and lactic acidosis. The most common genetic mutation associated with this syndrome is M.3243A>G. The main underlying mechanism of the disease relates to protein synthesis, energy depletion, and nitric oxide deficiency. Controlling disease complications and improving patient quality of life are the primary aims of treatment options.
CASE PRESENTATION
A 28-year-old Arabic female visited Al-Amiri Hospital in Kuwait. The patient was newly diagnosed with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode syndrome following her admission as a case of status epilepticus requiring further investigation. The patient's seizures were controlled, and she was evaluated to rule out the most serious complications by carrying out appropriate clinical, laboratory, and radiological imaging. The patient was discharged from the hospital after 2 weeks with a follow-up plan.
CONCLUSION
This case report emphasizes the importance of considering mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode syndrome as a potential cause of status epilepticus with lactic acidosis in a young female patient with a past history of stroke-like episodes. It also stresses the most important workup to rule out every possible life-threatening complication to improve patients' lives.
Topics: Acidosis, Lactic; Adult; Female; Humans; MELAS Syndrome; Nitric Oxide; Quality of Life; Status Epilepticus; Stroke
PubMed: 36210452
DOI: 10.1186/s13256-022-03613-2 -
Journal of the American College of... Oct 2022The heart is commonly involved in maternally inherited mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome caused by the...
BACKGROUND
The heart is commonly involved in maternally inherited mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome caused by the MT-TL1 m.3243A>G mutation of the mitochondrial DNA. Heart transplantation (HTx) is controversial and has rarely been performed with conflicting results.
OBJECTIVES
We analyzed factors preventing HTx in consecutive adult patients with MELAS cardiomyopathy diagnosed and followed during the last 23 years in our HTx referral center.
METHODS
The series consists of 14 unrelated adult probands who were referred for evaluation of cardiomyopathy from 1998 to 2021. None had a suspected diagnosis of MELAS before referral. All patients underwent clinical and genetic visit and counseling, mitochondrial DNA sequencing, cardiovascular investigation (including right heart catheterization and endomyocardial biopsy in 10), multidisciplinary assessment, and biochemical tests. Family screening identified 2 affected relatives.
RESULTS
The cardiac phenotype was characterized by hypertrophic, concentric, nonobstructive cardiomyopathy that often evolved into a dilated cardiomyopathy-like phenotype. Of the 14 probands, 7 were potential candidates for HTx, 2 for heart and kidney Tx, and 1 was on the active HTx list for 3 years. None of the 10 probands underwent HTx. One is currently being evaluated for HTx. All had diabetes, hearing loss, and myopathy, and 10 had chronic kidney disease and progressive encephalomyopathy. During follow-up, 10 died from heart failure associated with multiorgan failure within 5 years of the genetic diagnosis.
CONCLUSIONS
High risk of stroke-like episodes, chronic kidney disease, and wasting myopathy in MELAS patients prevents activation of plans for HTx. As a result, the management of their cardiomyopathy in this syndromic context remains an unmet clinical need.
Topics: Cardiomyopathies; DNA, Mitochondrial; Heart Transplantation; Humans; MELAS Syndrome; Muscular Diseases; Mutation; Renal Insufficiency, Chronic
PubMed: 36202533
DOI: 10.1016/j.jacc.2022.04.067 -
World Journal of Clinical Cases Sep 2022Mitochondrial encephalomyopathy (ME) is a multisystem metabolic disease that primarily affects the central nervous system and skeletal muscle. It is caused by mutations...
BACKGROUND
Mitochondrial encephalomyopathy (ME) is a multisystem metabolic disease that primarily affects the central nervous system and skeletal muscle. It is caused by mutations in mitochondrial or nuclear DNA, resulting in abnormal mitochondrial structure and function and insufficient ATP synthesis. The most common subtype is mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode (MELAS) syndrome. In recent years, reports of MELAS syndrome have increased but familial cases are rare.
CASE SUMMARY
We report a case of familial MELAS syndrome. Cases 2 and 3 are sisters and case 1 is their nephew. All are short in stature and showed stroke-like episodes with rapid onset and no obvious symptoms such as paroxysmal headache, aphasia, or blurred vision. After admission, blood lactate levels were significantly higher than normal. The patients underwent magnetic resonance imaging of the head. Cases 1 and 2 were considered to have ME, whereas case 3 was considered to have a space-occupying lesion in the left temporal lobe. Pathological evaluation showed no obvious tumor cells in the brain lesions of case 3. Muscle biopsy or genetic test results were consistent with ME. The patients were diagnosed with MELAS syndrome and their symptoms improved with intravenous infusions of coenzyme Q10, coenzyme A, vitamin B, and vitamin C. At the 6 mo follow-up, there was no recurrence or progression.
CONCLUSION
When a patient has MELAS syndrome, familial MELAS syndrome should be considered if related family members have similar symptoms.
PubMed: 36186180
DOI: 10.12998/wjcc.v10.i27.9945 -
World Journal of Clinical Cases Aug 2022The mitochondrial respiratory chain defects have become the most common cause of neurometabolic disorders in children and adults, which can occur at any time in life,...
BACKGROUND
The mitochondrial respiratory chain defects have become the most common cause of neurometabolic disorders in children and adults, which can occur at any time in life, often associated with neurological dysfunction, and lead to chronic disability and premature death. Approximately one-third of patients with mitochondrial disease have biochemical defects involving multiple respiratory chain complexes, suggesting defects in protein synthesis within the mitochondria. We here report a child with gene mutations causing mitochondrial disease.
CASE SUMMARY
A girl, aged 3 years and 4 mo, had been unable to sit and crawl alone since birth, with obvious seizures and microcephaly. Brain magnetic resonance imaging showed symmetrical, flaky, long T1-weighted and low T2-weighted signals in the posterior part of the bilateral putamen with a high signal shadow. T2 fluid-attenuated inversion recovery imaging showed a slightly high signal and diffusion-weighted imaging showed an obvious high signal. Whole-exome gene sequencing revealed a compound heterozygous mutation in the gene, c.1163(exon11)C>T and c.1940(exon20)C>T, which was derived from the parents. The child was diagnosed with combined oxidative phosphorylation deficiency type 20.
CONCLUSION
In this patient, mitochondrial disorders including Leigh syndrome and MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) were ruled out, and combined oxidative phosphorylation deficiency type 20 was diagnosed, expanding the phenotypic spectrum of the disease.
PubMed: 36157797
DOI: 10.12998/wjcc.v10.i24.8749 -
Annals of Medicine and Surgery (2012) Sep 2022The syndrome of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) is one of the most common inherited mitochondrial disorders.
INTRODUCTION
The syndrome of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) is one of the most common inherited mitochondrial disorders.
PRESENTATION OF CASE
A 33- year-old male was admitted due to edema, urinary retention, and reduce urinary output. The medical history included a pigmentary retinopathy (PR) at age of 22 and uveitis at age of 30, which were both treated with prednisolone. At age of 32, unapparent bilateral sensorineural hearing loss (SNHL) and symmetric basal ganglia calcifications were observed in neurologic study, and received prednisolone for the diagnosis of migraine and undefined vasculitis. Also, he described a right transient ischemic stroke (TIA) in the past 4 months. His family history included a dead brother, who had nearly similar components. Physical exam on admission corresponded with parkinsonism. The status points to MELAS but the genetic test was not available. Additional tests were applied, excluding all other disorders. Lactate was normal in serum and CSF. Kidney tests revealed a nephrotic syndrome and glomerulopathy, and the biopsy showed a single hyalinized glomerulus, which most likely suggests focal segmental glomerulosclerosis (FSGS). Muscle biopsy showed ragged red fibers.
CONCLUSION
Here, we report a challenging case of MELAS syndrome with rare manifestations including uveitis, PR, parkinsonism, and FSGS in the absence of lactic acidosis with unapparent muscle or hearing impairments. Since, clinicians might misdiagnose MELAS as vasculitis or other disorders due to its heterogeneous presentations, a proper investigations should guide the diagnosis of these conditions to reduce the delay of diagnosis and ineffective treatments.
PubMed: 36147056
DOI: 10.1016/j.amsu.2022.104483 -
Biology Sep 2022Advances in data acquisition via high resolution genomic, transcriptomic, proteomic and metabolomic platforms have driven the discovery of the underlying factors... (Review)
Review
Advances in data acquisition via high resolution genomic, transcriptomic, proteomic and metabolomic platforms have driven the discovery of the underlying factors associated with metabolic disorders (MD) and led to interventions that target the underlying genetic causes as well as lifestyle changes and dietary regulation. The review focuses on fourteen of the most widely studied inherited MD, which are familial hypercholesterolemia, Gaucher disease, Hunter syndrome, Krabbe disease, Maple syrup urine disease, Metachromatic leukodystrophy, Mitochondrial encephalopathy lactic acidosis stroke-like episodes (MELAS), Niemann-Pick disease, Phenylketonuria (PKU), Porphyria, Tay-Sachs disease, Wilson's disease, Familial hypertriglyceridemia (F-HTG) and Galactosemia based on genome wide association studies, epigenetic factors, transcript regulation, post-translational genetic modifications and biomarker discovery through metabolomic studies. We will delve into the current approaches being undertaken to analyze metadata using bioinformatic approaches and the emerging interventions using genome editing platforms as applied to animal models.
PubMed: 36138787
DOI: 10.3390/biology11091308 -
The Neurologist May 2023The mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a matrilineal hereditary multisystem disease caused by mutations in the...
INTRODUCTION
The mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a matrilineal hereditary multisystem disease caused by mutations in the mitochondrial DNA. Although the initial diagnostic criteria correlate with a range of clinical phenotypes, including clinical onset after the age of 40, there is still lack of a unified single diagnostic standard for MELAS.
CASE REPORT
A 71-year-old female patient with recurrent stroke was reported. Magnetic resonance imaging showed a cerebral gyrus-like diffusion weighted imaging high signal lesion in the parietal-occipital lobe and the area of this lesion expanded with disease progression. The MRS result showed significantly inverted Lac/Lip peaks. The nucleic acid sequencing result displayed a MT-TWm.5541C>T mutation, and a 12.86% mutation rate in the blood sample. The patient had a 6-year history of type 2 diabetes.
CONCLUSION
Patients with the MELAS syndrome may present with a variety of clinical manifestations. Our data demonstrated that, for patients with atypical cerebral infarction and suspected MELAS syndrome, gene sequencing and muscle biopsy should be performed in time. This case provides a reference for the diagnostic criteria of MELAS syndrome.
Topics: Female; Humans; Aged; Acidosis, Lactic; MELAS Syndrome; Diabetes Mellitus, Type 2; Stroke; Mutation; DNA, Mitochondrial; Cerebral Infarction
PubMed: 36125978
DOI: 10.1097/NRL.0000000000000457