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Asian Journal of Surgery Oct 2020
Topics: Carbon Dioxide; DNA, Mitochondrial; Endoscopy; Genotype; Humans; Lipoma; MERRF Syndrome; Male; Middle Aged; Mutation; Subcutaneous Tissue; Treatment Outcome
PubMed: 32631623
DOI: 10.1016/j.asjsur.2020.06.011 -
Journal of Neurology Nov 2020The mitochondrial tRNA (mt-tRNA) mutation is initially associated with myoclonic epilepsy and ragged-red fibers (MERRF). The clinical, laboratory, morphologic and...
The mitochondrial tRNA (mt-tRNA) mutation is initially associated with myoclonic epilepsy and ragged-red fibers (MERRF). The clinical, laboratory, morphologic and molecular findings from 22 mt-tRNA mutation carriers from local database in East China were analyzed retrospectively. We identified 13 symptomatic and 9 asymptomatic individuals with a known pathogenic mitochondrial tRNA mutation. The most common mutations were m.8344 A>G (81.8%), m.8363G>A (9.1%), m.8356 T>C (4.5%) and m.8356 T>G (4.5%). The degree of mutation heteroplasmy in blood was high both in symptomatic (mean 64.5%, range 41-82%) and asymptomatic individuals (mean 53.1%, range 21-78%). Age at onset ranged from 6 year-old to the age of 66 years (mean 35.8 ± 16.4 years old). The most frequent symptoms were muscle weakness (76.9%), exercise intolerance (76.9%), elevated creatine kinase levels (61.5%), peripheral neuropathy (69.2%) and cerebellar ataxia (61.5%), while myoclonus was only present in 23.1% of symptomatic patients. A diagnosis of mitochondrial myopathy (MM) and neuropathy ataxia and retinitis pigmentosa (NARP/NARP-like) syndrome was made in 77% of symptomatic patients, whereas the classic syndrome of myoclonic epilepsy with ragged-red fibers (MERRF) was rare (23%). In this cohort of patients with mt-tRNA mutation, more than one third of our patients did not develop signs and symptoms of central nervous system involvement even in later stages of the disease, indicating the necessity to investigate the mt-tRNA gene in 'pure' mitochondrial 'myo-neuropathy'.
Topics: Child; China; DNA, Mitochondrial; Humans; Lysine; MERRF Syndrome; Mutation; Peripheral Nervous System Diseases; RNA, Transfer; RNA, Transfer, Lys; Retrospective Studies
PubMed: 32577866
DOI: 10.1007/s00415-020-10017-z -
Journal of Neuromuscular Diseases 2020Neuropathies in Myoclonic Epilepsy with Ragged Red Fibers (MERRF) syndrome are frequent but ganglionopathies have never been reported. We retrospectively identified 24...
Neuropathies in Myoclonic Epilepsy with Ragged Red Fibers (MERRF) syndrome are frequent but ganglionopathies have never been reported. We retrospectively identified 24 patients with MERRF mutations in the neuromuscular center Nord/Est/Ile de France (Pitié-Salpêtrière, Paris, France). Seventeen nerve conduction studies (NCS) were available. Five patients had MERRF syndrome and ganglionopathy, a pure sensory neuropathy. All of them displayed ataxia and mild clinical sensory abnormalities. Ganglionopathies have been reported in mitochondrial diseases but never in MERRF syndrome. We suggest that patients presenting with ganglionopathy, especially if associated with myopathy, lipomatosis or epilepsy, should be screened for MERRF mutations.
Topics: Adult; Ataxia; Ganglia, Spinal; Humans; MERRF Syndrome; Neural Conduction; Peripheral Nervous System Diseases; Retrospective Studies; Sensation Disorders
PubMed: 32538863
DOI: 10.3233/JND-200513 -
Asian Journal of Surgery Aug 2020
Topics: Connective Tissue Diseases; Dermatologic Surgical Procedures; Humans; Laparoscopy; Lipomatosis, Multiple Symmetrical; MERRF Syndrome; Male; Middle Aged; Subcutaneous Tissue; Surgery, Plastic
PubMed: 32456962
DOI: 10.1016/j.asjsur.2020.04.012 -
Neurology India 2020Neurological diseases can be due to direct diseases of the central nervous system (CNS) or peripheral nervous system (PNS) or be a bystander syndrome of systemic...
INTRODUCTION
Neurological diseases can be due to direct diseases of the central nervous system (CNS) or peripheral nervous system (PNS) or be a bystander syndrome of systemic diseases. Treatment options depend on the cause. Toxic, metabolic and nutritional, and immune-mediated consequences of clinically occult neoplasms produce a spectrum of neurological diseases, recognition of which has therapeutic and prognostic importance.
PATIENTS AND METHODS
Children, as well as adults who presented to the authors in the last 5 years with neurological diseases and later their diseases could be diagnosed or attributed to neoplasms which were occult, were included for the study.
OBSERVATION
28 patients were seen by the authors in the last 5 years with neurological manifestation and hidden tumor. Maximum incidence was in the age of above 60 years followed by the age group of 21-40 years. The commonest neurological presentation was muscle and nerve in adults and seizure in children.
DISCUSSION
Short duration, rapid progression, severe weight loss, and poor response to treatment given for nontumor associated neurological syndrome are the red flags which point to the diagnosis.
CONCLUSION
Seizures and psychosis formed the commonest features in children, muscle and nerve in adults. Short duration, rapid progression, and resistance to treatment are the markers for possible underlying neoplasm.
Topics: Adenoma; Adolescent; Adult; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Ataxia; Carcinoma; Child; Dementia; Diagnosis, Differential; Diagnostic Errors; Female; Ganglioneuroma; Humans; Hypokalemic Periodic Paralysis; Lipoma; Lymphoma, Non-Hodgkin; MERRF Syndrome; Male; Middle Aged; Myoclonic Epilepsy, Juvenile; Neoplasms; Nervous System Diseases; Neuroblastoma; Opsoclonus-Myoclonus Syndrome; Ovarian Neoplasms; POEMS Syndrome; Pancreatic Neoplasms; Paraneoplastic Syndromes, Nervous System; Parathyroid Neoplasms; Parkinsonian Disorders; Plasmacytoma; Polymyositis; Stomach Neoplasms; Subacute Combined Degeneration; Teratoma; Thymus Neoplasms; Young Adult
PubMed: 32415012
DOI: 10.4103/0028-3886.280647 -
Annales D'endocrinologie Jun 2020While the most frequent mutation responsible for mitochondrial diabetes is the point mutation m.3243 A>G of mitochondrial DNA (mtDNA), few data are available about the...
OBJECTIVE
While the most frequent mutation responsible for mitochondrial diabetes is the point mutation m.3243 A>G of mitochondrial DNA (mtDNA), few data are available about the role of rare mtDNA mutations in the pathophysiology of diabetes. The main objective of our study was to describe the phenotypic characteristics of patients suffering from diabetes linked to rare mtDNA mutations.
RESEARCH DESIGN AND METHODS
We performed a post-hoc analysis of a prospective multicenter cohort of 743 patients with mitochondrial disorder (previously published by the French Network of Mitochondrial Diseases), associated to a literature review of the PubMed database from 1992 to May 2016. We extracted all reported patients with diabetes and identified rare mtDNA mutations and described their clinical and metabolic phenotypes.
RESULTS
The 50 identified patients (10 from the princeps study; 40 from the review of the literature) showed a heterogeneous metabolic phenotype in terms of age, symptoms prior to diagnosis, treatments, and associated clinical and biological signs. However, neurological symptoms were more frequent in case of rare mtDNA mutations compared to the classical m.3243 A>G mutation (P=0.024). In contrast, deafness (65% vs. 95%, P=3.7E-5), macular pattern dystrophy (20% vs. 86%, P=1.6E-10) and nephropathy (8% vs. 28%, P=0.018) were significantly less frequent than in case of the classical m.3243 A>G mutation.
CONCLUSION
Although no specific metabolic phenotype could be identified suggesting or eliminating implication of rare mtDNA mutations in diabetes, clinical phenotypes featured more frequent neurological signs.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Cohort Studies; DNA Mutational Analysis; DNA, Mitochondrial; Deafness; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; France; Gene Frequency; Genetic Association Studies; Humans; Infant; Infant, Newborn; MERRF Syndrome; Male; Middle Aged; Mitochondrial Diseases; Mutation; Phenotype; Prospective Studies
PubMed: 32409007
DOI: 10.1016/j.ando.2020.04.007 -
Neurology May 2020
Topics: Adolescent; Brain; DNA, Mitochondrial; Epilepsies, Myoclonic; Female; Humans; MERRF Syndrome; Mutation; Phenotype
PubMed: 32327493
DOI: 10.1212/WNL.0000000000009438 -
Mitochondrion May 2020A 56-year-old female, diagnosed as a carrier of the mitochondrial DNA mutation (MTTK c.8344A > G) associated with the MERRF (myoclonic epilepsy with ragged red fibers)...
Self-initiated lifestyle interventions lead to potential insight into an effective, alternative, non-surgical therapy for mitochondrial disease associated multiple symmetric lipomatosis.
BACKGROUND
A 56-year-old female, diagnosed as a carrier of the mitochondrial DNA mutation (MTTK c.8344A > G) associated with the MERRF (myoclonic epilepsy with ragged red fibers) syndrome, presented with a relatively uncommon but well-known phenotypic manifestation: severe multiple symmetric lipomatosis (MSL). After surgical resection of three kilograms of upper mid-back lipomatous tissue, the patient experienced a significant decline in her functional capacity and quality of life, which ultimately resulted in her placement on long-term disability.
METHODS
Dissatisfied with the available treatment options centered on additional resection surgeries, given the high probability of lipoma regrowth, the patient independently researched and applied alternative therapies that centred on a carbohydrate-restricted diet and a supervised exercise program.
RESULTS
The cumulative effect of her lifestyle interventions resulted in the reversal of her MSL and her previously low quality of life. She met all her personal goals by the one-year mark, including reduced size of the residual post-surgical lipomas, markedly enhanced exercise tolerance, and return to work. She continues to maintain her interventions and to experience positive outcomes at the two-year mark.
INTERPRETATION
This case report documents the timing and nature of lifestyle interventions in relation to the reversal in growth pattern of her previously expanding and debilitating lipomas. The profound nature of the apparent benefit on lipoma growth demonstrates the intervention's potential as a new feasible non-surgical therapy for mitochondrial-disease-associated MSL, and justifies its systematic study. We also describe how this case has inspired the care team to re-examine its approach to involved patients.
Topics: Complementary Therapies; Diet, Carbohydrate-Restricted; Exercise Therapy; Female; Healthy Lifestyle; Humans; Lipomatosis, Multiple Symmetrical; MERRF Syndrome; Middle Aged; Return to Work; Treatment Outcome
PubMed: 32234544
DOI: 10.1016/j.mito.2020.03.009 -
The FEBS Journal Sep 2020Various pathogenic variants in both mitochondrial tRNA and Phenylalanyl-tRNA synthetase mitochondrial protein coding gene (FARS2) gene encoding for the human...
Various pathogenic variants in both mitochondrial tRNA and Phenylalanyl-tRNA synthetase mitochondrial protein coding gene (FARS2) gene encoding for the human mitochondrial PheRS have been identified and associated with neurological and/or muscle-related pathologies. An important Guanine-34 (G34)A anticodon mutation associated with myoclonic epilepsy with ragged red fibers (MERRF) syndrome has been reported in hmit-tRNA . The majority of G34 contacts in available aaRSs-tRNAs complexes specifically use that base as an important tRNA identity element. The network of intermolecular interactions providing its specific recognition also largely conserved. However, their conservation depends also on the invariance of the residues in the anticodon binding domain (ABD) of human mitochondrial Phenylalanyl-tRNA synthetase (hmit-PheRS). A defect in recognition of the anticodon of tRNA may happen not only because of G34A mutation, but also due to mutations in the ABD. Indeed, a pathogenic mutation in FARS2 has been recently reported in a 9-year-old female patient harboring a p.Asp364Gly mutation. Asp364 is hydrogen bonded (HB) to G34 in WT hmit-PheRS. Thus, there are two pathogenic variants disrupting HB between G34 and Asp364: one is associated with G34A mutation, and the other with Asp364Gly mutation. We have measured the rates of tRNA aminoacylation catalyzed by WT hmit-PheRS and mutant enzymes. These data ranked the residues making a HB with G34 according to their contribution to activity and the signal transduction pathway in the hmit-PheRS-tRNA complex. Furthermore, we carried out extensive MD simulations to reveal the interdomain contact topology on the dynamic trajectories of the complex, and gaining insight into the structural and dynamic integrity effects of hmit-PheRS complexed with tRNA . DATABASE: Structural data are available in PDB database under the accession number(s): 3CMQ, 3TUP, 5MGH, 5MGV.
Topics: Amino Acid Substitution; Anticodon; Aspartic Acid; Child; Consanguinity; DNA, Mitochondrial; Disease Progression; Female; Genetic Pleiotropy; Guanine; Humans; Hydrogen Bonding; MERRF Syndrome; Mitochondrial Proteins; Models, Molecular; Molecular Dynamics Simulation; Motion; Mutation, Missense; Paraparesis, Spastic; Phenotype; Phenylalanine-tRNA Ligase; Point Mutation; Protein Conformation; Protein Domains; RNA, Transfer, Phe
PubMed: 32115907
DOI: 10.1111/febs.15268 -
European Annals of Otorhinolaryngology,... May 2020
Topics: Genotype; Humans; MERRF Syndrome; Phenotype
PubMed: 32063498
DOI: 10.1016/j.anorl.2018.12.003