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International Journal of Molecular... Oct 2022Primary mitochondrial diseases are relatively common inborn errors of energy metabolism, with a combined prevalence of 1 in 4300. These disorders typically affect... (Review)
Review
Primary mitochondrial diseases are relatively common inborn errors of energy metabolism, with a combined prevalence of 1 in 4300. These disorders typically affect tissues with high energy requirements, including the brain. Epilepsy affects >1% of the worldwide population, making it one of the most common neurological illnesses; it may be the presenting feature of a mitochondrial disease, but is often part of a multisystem clinical presentation. The major genetic causes of mitochondrial epilepsy are mutations in mitochondrial DNA and in the nuclear-encoded gene POLG. Treatment of mitochondrial epilepsy may be challenging, often representing a poor prognostic feature. This narrative review will cover the most recent advances in the field of mitochondrial epilepsy, from pathophysiology and genetic etiologies to phenotype and treatment options.
Topics: Humans; Neurologists; Mitochondrial Diseases; DNA, Mitochondrial; Epilepsy; Mitochondria; Mutation
PubMed: 36362003
DOI: 10.3390/ijms232113216 -
Annales D'endocrinologie Jun 2024Lipomatoses are benign proliferation of adipose tissue. Lipomas (benign fat tumors) are the most common component of lipomatosis. They may be unique or multiple,... (Review)
Review
Lipomatoses are benign proliferation of adipose tissue. Lipomas (benign fat tumors) are the most common component of lipomatosis. They may be unique or multiple, encapsulated or not, subcutaneous or sometimes visceral. In some cases, they form large areas of non-encapsulated fat hypertrophy, with a variable degree of fibrosis. They can develop despite the absence of obesity. They may be familial or acquired. At difference with lipodystrophy syndromes, they are not associated with lipoatrophy areas, except in some rare cases such as type 2 familial partial lipodystrophy syndromes (FPLD2). Their metabolic impact is variable in part depending on associated obesity. They may have functional or aesthetic consequences. Lipomatosis may be isolated, be part of a syndrome, or may be visceral. Isolated lipomatoses include multiple symmetrical lipomatosis (Madelung disease or Launois-Bensaude syndrome), familial multiple lipomatosis, the painful Dercum's disease also called Adiposis Dolorosa or Ander syndrome, mesosomatic lipomatosis also called Roch-Leri lipomatosis, familial angiolipomatosis, lipedema and hibernomas. Syndromic lipomatoses include PIK3CA-related disorders, Cowden/PTEN hamartomas-tumor syndrome, some lipodystrophy syndromes, and mitochondrial diseases, especially MERRF, multiple endocrine neoplasia type 1, neurofibromatosis type 1, Wilson disease, Pai or Haberland syndromes. Finally, visceral lipomatoses have been reported in numerous organs and sites: pancreatic, adrenal, abdominal, epidural, mediastinal, epicardial… The aim of this review is to present the main types of lipomatosis and their physiopathological component, when it is known.
Topics: Humans; Lipomatosis; Lipoma; Lipomatosis, Multiple Symmetrical; Lipodystrophy; Adipose Tissue; Adiposis Dolorosa
PubMed: 38871514
DOI: 10.1016/j.ando.2024.05.003 -
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 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 -
Seizure Aug 2017Myoclonic epilepsy with ragged-red fibers (MERRF) syndrome is a rare syndromic mitochondrial disorder (MID) with a broad phenotypic but narrow genotypic heterogeneity.... (Review)
Review
Myoclonic epilepsy with ragged-red fibers (MERRF) syndrome is a rare syndromic mitochondrial disorder (MID) with a broad phenotypic but narrow genotypic heterogeneity. One of the predominant phenotypic features in addition to myopathy is epilepsy. The most frequent seizure type in MERRF is generalised myoclonic seizure but also focal myoclonic, focal atonic, generalised tonic-clonic, generalised atonic, generalised myoclonic-atonic, typical absences, or tonic-clonic seizures of unknown onset have been reported. There are no guidelines available for the management of epilepsy in MERRF syndrome but several expert opinions and general recommendations for the treatment of mitochondrial epilepsy have been published. According to these recommendations the antiepileptic drugs (AEDs) of choice are levetiracetam, topiramate, zonisamide, piracetam, and benzodiazepines. Perampanel has not been applied in MERRF patients but is promising in non-mitochondrial myoclonic epilepsy. Mitochondrion-toxic agents, including mitochondrion-toxic AEDs, such as valproate, carbamazepine, phenytoin, and barbiturates, should be avoided as well as AEDs potentially enhancing the frequency of myoclonus, such as phenytoin, carbamazepine, lamotrigine, vigabatrin, tiagabine, gabapentin, pregabalin, and oxcarbazepine.
Topics: Anticonvulsants; Epilepsy; Humans; MERRF Syndrome
PubMed: 28686997
DOI: 10.1016/j.seizure.2017.06.010 -
Neurology India 2010Progressive myoclonic epilepsy (PME) is a disease complex and is characterized by the development of relentlessly progressive myoclonus, cognitive impairment, ataxia,... (Review)
Review
Progressive myoclonic epilepsy (PME) is a disease complex and is characterized by the development of relentlessly progressive myoclonus, cognitive impairment, ataxia, and other neurologic deficits. It encompasses different diagnostic entities and the common causes include Lafora body disease, neuronal ceroid lipofuscinoses, Unverricht-Lundborg disease, myoclonic epilepsy with ragged-red fiber (MERRF) syndrome, sialidoses, dentato-rubro-pallidal atrophy, storage diseases, and some of the inborn errors of metabolism, among others. Recent advances in this area have clarified molecular genetic basis, biological basis, and natural history, and also provided a rational approach to the diagnosis. Most of the large studies related to PME are from south India from a single center, National Institute of Mental Health and Neurological Sciences (NIMHANS), Bangalore. However, there are a few case reports and small series about Lafora body disease, neuronal ceroid lipofuscinoses and MERRF from India. We review the clinical and research experience of a cohort of PME patients evaluated at NIMHANS over the last two decades, especially the phenotypic, electrophysiologic, pathologic, and genetic aspects.
Topics: Cognition Disorders; Diagnostic Imaging; Electroencephalography; Humans; India; Muscle, Skeletal; Myoclonic Epilepsies, Progressive; Protein Tyrosine Phosphatases, Non-Receptor
PubMed: 20739785
DOI: 10.4103/0028-3886.68660 -
Epilepsia Sep 2012The mitochondrial respiratory chain is the final common pathway for energy production. Defects affecting this pathway can give rise to disease that presents at any age... (Review)
Review
The mitochondrial respiratory chain is the final common pathway for energy production. Defects affecting this pathway can give rise to disease that presents at any age and affects any tissue. However, irrespective of genetic defect, epilepsy is common and there is a significant risk of status epilepticus. This review summarizes our current understanding of the epilepsy that occurs in mitochondrial disease, focusing on three of the most common disorders: mitochondrial myopathy encephalopathy, lactic acidosis and stroke-like episodes (MELAS), myoclonus epilepsy and ragged-red fibers (MERRF), and polymerase gamma (POLG) related disease. In addition, we review the pathogenesis and possible treatment of these disorders.
Topics: Anticonvulsants; Epilepsy; Humans; MERRF Syndrome; Mitochondria; Mitochondrial Diseases; Mitochondrial Encephalomyopathies
PubMed: 22946726
DOI: 10.1111/j.1528-1167.2012.03618.x -
Case Reports in Neurological Medicine 2020Although endocrinologic involvement and epilepsy are frequent features of myoclonic epilepsy with ragged-red fibers (MERRF), polycystic ovary syndrome (PCOS) and...
OBJECTIVES
Although endocrinologic involvement and epilepsy are frequent features of myoclonic epilepsy with ragged-red fibers (MERRF), polycystic ovary syndrome (PCOS) and photosensitive epilepsy have not been reported. . A 32-year-old female was diagnosed with MERRF at age 19 y upon presence of the four canonical features and the variant m.8344A > G in () (blood heteroplasmy rate: 50%). She experienced recurrent photosensitive focal and generalised seizures since age 19 y, which could be triggered by flickering light or by looking at small stones, leaves, or dirty snow on the ground. Since the last 42 months, she was seizure-free upon levetiracetam (4000 mg/d), clonazepam (1.5 mg/d), and topiramate (25 mg/d). Additionally, she suffered from secondary amenorrhoea since adolescence. She was married between ages 19 y and 25 y but did not get pregnant. PCOS was diagnosed and treated with desogestrel plus estradiol. Nonetheless, the course was progressive, particularly with regard to ataxia, myocloni, and myopathy.
CONCLUSIONS
The phenotypic spectrum of MERRF is broader than anticipated and may additionally include PCOS and photosensitive epilepsy. PCOS in MERRF may respond to hormone substitution and photosensitive epilepsy to levetiracetam, clonazepam, and topiramate.
PubMed: 33062354
DOI: 10.1155/2020/8876272