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Neurology International Apr 2022Ataxia is increasingly being recognized as a cardinal manifestation in primary mitochondrial diseases (PMDs) in both paediatric and adult patients. It can be caused by... (Review)
Review
Ataxia is increasingly being recognized as a cardinal manifestation in primary mitochondrial diseases (PMDs) in both paediatric and adult patients. It can be caused by disruption of cerebellar nuclei or fibres, its connection with the brainstem, or spinal and peripheral lesions leading to proprioceptive loss. Despite mitochondrial ataxias having no specific defining features, they should be included in hereditary ataxias differential diagnosis, given the high prevalence of PMDs. This review focuses on the clinical and neuropathological features and genetic background of PMDs in which ataxia is a prominent manifestation.
PubMed: 35466209
DOI: 10.3390/neurolint14020028 -
Cells Feb 2022Mitochondria are cytoplasmic organelles, which generate energy as heat and ATP, the universal energy currency of the cell. This process is carried out by coupling... (Review)
Review
Mitochondria are cytoplasmic organelles, which generate energy as heat and ATP, the universal energy currency of the cell. This process is carried out by coupling electron stripping through oxidation of nutrient substrates with the formation of a proton-based electrochemical gradient across the inner mitochondrial membrane. Controlled dissipation of the gradient can lead to production of heat as well as ATP, via ADP phosphorylation. This process is known as oxidative phosphorylation, and is carried out by four multiheteromeric complexes (from I to IV) of the mitochondrial respiratory chain, carrying out the electron flow whose energy is stored as a proton-based electrochemical gradient. This gradient sustains a second reaction, operated by the mitochondrial ATP synthase, or complex V, which condensates ADP and Pi into ATP. Four complexes (CI, CIII, CIV, and CV) are composed of proteins encoded by genes present in two separate compartments: the nuclear genome and a small circular DNA found in mitochondria themselves, and are termed mitochondrial DNA (mtDNA). Mutations striking either genome can lead to mitochondrial impairment, determining infantile, childhood or adult neurodegeneration. Mitochondrial disorders are complex neurological syndromes, and are often part of a multisystem disorder. In this paper, we divide the diseases into those caused by mtDNA defects and those that are due to mutations involving nuclear genes; from a clinical point of view, we discuss pediatric disorders in comparison to juvenile or adult-onset conditions. The complementary genetic contributions controlling organellar function and the complexity of the biochemical pathways present in the mitochondria justify the extreme genetic and phenotypic heterogeneity of this new area of inborn errors of metabolism known as 'mitochondrial medicine'.
Topics: Adenosine Diphosphate; Adenosine Triphosphate; Adult; Child; DNA, Mitochondrial; Humans; Mitochondria; Protons
PubMed: 35203288
DOI: 10.3390/cells11040637 -
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 -
A&A Practice Sep 2021
Topics: Documentation; Epilepsies, Myoclonic; Humans; MERRF Syndrome; Mutation
PubMed: 34529593
DOI: 10.1213/XAA.0000000000001525 -
A&A Practice Sep 2021
Topics: Documentation; Humans; MERRF Syndrome; Mutation
PubMed: 34529589
DOI: 10.1213/XAA.0000000000001526 -
Internal Medicine (Tokyo, Japan) Feb 2022We herein report a case of myoclonic epilepsy with ragged-red fibers (MERRF) harboring a novel variant in mitochondrial cysteine transfer RNA (MT-TC). A 68-year-old...
We herein report a case of myoclonic epilepsy with ragged-red fibers (MERRF) harboring a novel variant in mitochondrial cysteine transfer RNA (MT-TC). A 68-year-old woman presented with progressive myoclonic epilepsy with optic atrophy and peripheral neuropathy. A skin biopsy revealed p62-positive intranuclear inclusions. No mutations were found in the causative genes for diseases known to be related to intranuclear inclusions; however, a novel variant in MT-TC was found. The association between intranuclear inclusions and this newly identified MERRF-associated variant is unclear; however, the rare complication of intranuclear inclusions in a patient with typical MERRF symptoms should be noted for future studies.
Topics: Aged; DNA, Mitochondrial; Female; Humans; Intranuclear Inclusion Bodies; MERRF Syndrome; Mitochondria; Mutation; Optic Atrophy
PubMed: 34433719
DOI: 10.2169/internalmedicine.7767-21 -
Pathology International Aug 2021
Topics: Autopsy; Brain; Humans; MELAS Syndrome; MERRF Syndrome
PubMed: 34106496
DOI: 10.1111/pin.13111 -
Journal of Clinical Medicine Mar 2021In the last ten years, the knowledge of the genetic basis of mitochondrial diseases has significantly advanced. However, the vast phenotypic variability linked to... (Review)
Review
In the last ten years, the knowledge of the genetic basis of mitochondrial diseases has significantly advanced. However, the vast phenotypic variability linked to mitochondrial disorders and the peculiar characteristics of their genetics make mitochondrial disorders a complex group of disorders. Although specific genetic alterations have been associated with some syndromic presentations, the genotype-phenotype relationship in mitochondrial disorders is complex (a single mutation can cause several clinical syndromes, while different genetic alterations can cause similar phenotypes). This review will revisit the most common syndromic pictures of mitochondrial disorders, from a clinical rather than a molecular perspective. We believe that the new phenotype definitions implemented by recent large multicenter studies, and revised here, may contribute to a more homogeneous patient categorization, which will be useful in future studies on natural history and clinical trials.
PubMed: 33802970
DOI: 10.3390/jcm10061249 -
BMJ Case Reports Mar 2021We present a rare case of myoclonic epilepsy with ragged red fibres with high level of heteroplasmy presenting with optic neuropathy and a rare phenotype of lipomatosis....
We present a rare case of myoclonic epilepsy with ragged red fibres with high level of heteroplasmy presenting with optic neuropathy and a rare phenotype of lipomatosis. Cutaneous lipomas are typically thought of as a benign/isolated entity and this case emphasises importance of considering mitochondrial disease in all patients with lipomatosis especially in the presence of other systemic abnormalities.
Topics: DNA, Mitochondrial; Humans; Lipomatosis; Lipomatosis, Multiple Symmetrical; MERRF Syndrome; Mutation; Optic Nerve Diseases
PubMed: 33766967
DOI: 10.1136/bcr-2020-240463