Journal of Clinical Medicine

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Open AccessEditorial

Mitochondrial Medicine in the COVID-19 Era

by Daniele Orsucci

J. Clin. Med. 2021, 10(22), 5235; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10225235 - 10 Nov 2021

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Abstract

Mitochondrial disorders are a remarkably complex group of diseases caused by impairment of the mitochondrial respiratory chain (or electron transport chain) [...] Full article

(This article belongs to the Special Issue Mitochondrial Disorders: Molecular, Clinical and Therapeutic Advances)

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14 pages, 1063 KiB

Open AccessArticle

Clinical, Histological, and Genetic Features of 25 Patients with Autosomal Dominant Progressive External Ophthalmoplegia (ad-PEO)/PEO-Plus Due to TWNK Mutations

by Laura Bermejo-Guerrero, Carlos Pablo de Fuenmayor-Fernández de la Hoz, Pablo Serrano-Lorenzo, Alberto Blázquez-Encinar, Gerardo Gutiérrez-Gutiérrez, Laura Martínez-Vicente, Lucía Galán-Dávila, Jorge García-García, Joaquín Arenas, Nuria Muelas, Aurelio Hernández-Laín, Cristina Domínguez-González and Miguel A. Martín

J. Clin. Med. 2022, 11(1), 22; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11010022 - 22 Dec 2021

Cited by 5 | Viewed by 2737

Abstract

Autosomal dominant mutations in the TWNK gene, which encodes a mitochondrial DNA helicase, cause adult-onset progressive external ophthalmoplegia (PEO) and PEO-plus presentations. In this retrospective observational study, we describe clinical and complementary data from 25 PEO patients with mutations in TWNK recruited from [...] Read more.

Autosomal dominant mutations in the TWNK gene, which encodes a mitochondrial DNA helicase, cause adult-onset progressive external ophthalmoplegia (PEO) and PEO-plus presentations. In this retrospective observational study, we describe clinical and complementary data from 25 PEO patients with mutations in TWNK recruited from the Hospital 12 de Octubre Mitochondrial Disorders Laboratory Database. The mean ages of onset and diagnosis were 43 and 63 years, respectively. Family history was positive in 22 patients. Ptosis and PEO (92% and 80%) were the most common findings. Weakness was present in 48%, affecting proximal limbs, neck, and bulbar muscles. Exercise intolerance was present in 28%. Less frequent manifestations were cardiac (24%) and respiratory (4%) involvement, neuropathy (8%), ataxia (4%), and parkinsonism (4%). Only 28% had mild hyperCKemia. All 19 available muscle biopsies showed signs of mitochondrial dysfunction. Ten different TWNK mutations were identified, with c.1361T>G (p.Val454Gly) and c.1070G>C (p.Arg357Pro) being the most common. Before definitive genetic confirmation, 56% of patients were misdiagnosed (36% with myasthenia, 20% with oculopharyngeal muscle dystrophy). Accurate differential diagnosis and early confirmation with appropriately chosen complementary studies allow genetic counseling and the avoidance of unnecessary treatments. Thus, mitochondrial myopathies must be considered in PEO/PEO-plus presentations, and particularly, TWNK is an important cause when positive family history is present. Full article

(This article belongs to the Special Issue Mitochondrial Disorders: Molecular, Clinical and Therapeutic Advances)

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9 pages, 1447 KiB

Open AccessArticle

Cerebellar White Matter Abnormalities in Charcot–Marie–Tooth Disease: A Combined Volumetry and Diffusion Tensor Imaging Analysis

by Sungeun Hwang, Chang-Hyun Park, Regina Eun-Young Kim, Hyeon Jin Kim, Yun Seo Choi, Sol-Ah Kim, Jeong Hyun Yoo, Ki Wha Chung, Byung-Ok Choi and Hyang Woon Lee

J. Clin. Med. 2021, 10(21), 4945; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10214945 - 26 Oct 2021

Cited by 3 | Viewed by 1952

Abstract

Charcot–Marie–Tooth disease (CMT) is a genetically heterogeneous hereditary peripheral neuropathy. Brain volumetry and diffusion tensor imaging (DTI) were performed in 47 controls and 47 CMT patients with PMP22 duplication (n = 10), MFN2 (n = 15), GJB1 (n = 11), [...] Read more.

Charcot–Marie–Tooth disease (CMT) is a genetically heterogeneous hereditary peripheral neuropathy. Brain volumetry and diffusion tensor imaging (DTI) were performed in 47 controls and 47 CMT patients with PMP22 duplication (n = 10), MFN2 (n = 15), GJB1 (n = 11), or NEFL mutations (n = 11) to investigate for structural changes in the cerebellum. Volume of cerebellar white matter (WM) was significantly reduced in CMT patients with NEFL mutations. Abnormal DTI findings were observed in the superior, middle, and inferior cerebellar peduncles, predominantly in NEFL mutations and partly in GJB1 mutations. Cerebellar ataxia was more prevalent in the NEFL mutation group (72.7%) than the GJB1 mutation group (9.1%) but was not observed in other genotypic subtypes, which indicates that structural cerebellar abnormalities were associated with the presence of cerebellar ataxia. However, NEFL and GJB1 mutations did not affect cerebellar gray matter (GM), and neither cerebellar GM nor WM abnormalities were observed in the PMP22 duplication or MFN2 mutation groups. We found structural evidence of cerebellar WM abnormalities in CMT patients with NEFL and GJB1 mutations and an association between cerebellar WM involvement and cerebellar ataxia in these genetic subtypes, especially in the NEFL subgroup. Therefore, we suggest that neuroimaging, such as MRI volumetry or DTI, for CMT patients could play an important role in detecting abnormalities of cerebellar WM. Full article

(This article belongs to the Special Issue Mitochondrial Disorders: Molecular, Clinical and Therapeutic Advances)

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12 pages, 1556 KiB

Open AccessArticle

Two Novel Variants in YARS2 Gene Are Responsible for an Extended MLASA Phenotype with Pancreatic Insufficiency

by Lidia Carreño-Gago, Diana Luz Juárez-Flores, Josep Maria Grau, Javier Ramón, Ester Lozano, Ferran Vila-Julià, Ramon Martí, Glòria Garrabou and Elena Garcia-Arumí

J. Clin. Med. 2021, 10(16), 3471; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10163471 - 5 Aug 2021

Cited by 6 | Viewed by 1954

Abstract

Pathogenic variants in the mitochondrial tyrosyl-tRNA synthetase gene (YARS2) were associated with myopathy, lactic acidosis, and sideroblastic anemia (MLASA). However, patients can present mitochondrial myopathy, with exercise intolerance and muscle weakness, leading from mild to lethal phenotypes. Genes implicated in mtDNA [...] Read more.

Pathogenic variants in the mitochondrial tyrosyl-tRNA synthetase gene (YARS2) were associated with myopathy, lactic acidosis, and sideroblastic anemia (MLASA). However, patients can present mitochondrial myopathy, with exercise intolerance and muscle weakness, leading from mild to lethal phenotypes. Genes implicated in mtDNA replication were studied by Next Generation Sequencing (NGS) and whole exome sequence with the TruSeq Rapid Exome kit (Illumina, San Diego, CA, USA). Mitochondrial protein translation was studied following the Sasarman and Shoubridge protocol and oxygen consumption rates with Agilent Seahorse XF24 Analyzer Mitostress Test, (Agilent, Santa Clara, CA, USA). We report two siblings with two novel compound heterozygous pathogenic variants in YARS2 gene: a single nucleotide deletion in exon 1, c.314delG (p.(Gly105Alafs*4)), which creates a premature stop codon in the amino acid 109, and a single nucleotide change in exon 5 c.1391T>C (p.(Ile464Thr)), that cause a missense variant in amino acid 464. We demonstrate the pathogenicity of these new variants associated with reduced YARS2 mRNA transcript, reduced mitochondrial protein translation and dysfunctional organelle function. These pathogenic variants are responsible for late onset MLASA, herein accompanied by pancreatic insufficiency, observed in both brothers, clinically considered as Pearson’s syndrome. Molecular study of YARS2 gene should be considered in patients presenting Pearson’s syndrome characteristics and MLASA related phenotypes. Full article

(This article belongs to the Special Issue Mitochondrial Disorders: Molecular, Clinical and Therapeutic Advances)

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11 pages, 2098 KiB

Open AccessArticle

The Diagnostic Approach to Mitochondrial Disorders in Children in the Era of Next-Generation Sequencing: A 4-Year Cohort Study

by Deborah Tolomeo, Daniele Orsucci, Claudia Nesti, Jacopo Baldacci, Roberta Battini, Claudio Bruno, Giorgia Bruno, Denise Cassandrini, Stefano Doccini, M. Alice Donati, Annarita Ferrari, Simona Fiori, Chiara Fiorillo, Renzo Guerrini, Francesco Mari, Martino Montomoli, Francesca Pochiero, Elena Procopio, Lucia Ruggiero, Simone Sampaolo, Federico Sicca, Chiara Ticci, Anna Rubegni and Filippo M. Santorelli Show full author list Hide full author list

J. Clin. Med. 2021, 10(15), 3222; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10153222 - 22 Jul 2021

Cited by 3 | Viewed by 2499

Abstract

Mitochondrial diseases (MDs) are a large group of genetically determined multisystem disorders, characterized by extreme phenotypic heterogeneity, attributable in part to the dual genomic control (nuclear and mitochondrial DNA) of the mitochondrial proteome. Advances in next-generation sequencing technologies over the past two decades [...] Read more.

Mitochondrial diseases (MDs) are a large group of genetically determined multisystem disorders, characterized by extreme phenotypic heterogeneity, attributable in part to the dual genomic control (nuclear and mitochondrial DNA) of the mitochondrial proteome. Advances in next-generation sequencing technologies over the past two decades have presented clinicians with a challenge: to select the candidate disease-causing variants among the huge number of data provided. Unfortunately, the clinical tools available to support genetic interpretations still lack specificity and sensitivity. For this reason, the diagnosis of MDs continues to be difficult, with the new “genotype first” approach still failing to diagnose a large group of patients. With the aim of investigating possible relationships between clinical and/or biochemical phenotypes and definitive molecular diagnoses, we performed a retrospective multicenter study of 111 pediatric patients with clinical suspicion of MD. In this cohort, the strongest predictor of a molecular (in particular an mtDNA-related) diagnosis of MD was neuroimaging evidence of basal ganglia (BG) involvement. Regression analysis confirmed that normal BG imaging predicted negative genetic studies for MD. Psychomotor regression was confirmed as an independent predictor of a definitive diagnosis of MD. The findings of this study corroborate previous data supporting a role for neuroimaging in the diagnostic approach to MDs and reinforce the idea that mtDNA sequencing should be considered for first-line testing, at least in specific groups of children. Full article

(This article belongs to the Special Issue Mitochondrial Disorders: Molecular, Clinical and Therapeutic Advances)

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15 pages, 1665 KiB

Open AccessArticle

Movement Disorders in Children with a Mitochondrial Disease: A Cross-Sectional Survey from the Nationwide Italian Collaborative Network of Mitochondrial Diseases

by Chiara Ticci, Daniele Orsucci, Anna Ardissone, Luca Bello, Enrico Bertini, Irene Bonato, Claudio Bruno, Valerio Carelli, Daria Diodato, Stefano Doccini, Maria Alice Donati, Claudia Dosi, Massimiliano Filosto, Chiara Fiorillo, Chiara La Morgia, Costanza Lamperti, Silvia Marchet, Diego Martinelli, Carlo Minetti, Maurizio Moggio, Tiziana Enrica Mongini, Vincenzo Montano, Isabella Moroni, Olimpia Musumeci, Elia Pancheri, Elena Pegoraro, Guido Primiano, Elena Procopio, Anna Rubegni, Roberta Scalise, Monica Sciacco, Serenella Servidei, Gabriele Siciliano, Costanza Simoncini, Deborah Tolomeo, Paola Tonin, Antonio Toscano, Flavia Tubili, Michelangelo Mancuso, Roberta Battini and Filippo Maria Santorelli Show full author list Hide full author list

J. Clin. Med. 2021, 10(10), 2063; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10102063 - 12 May 2021

Cited by 11 | Viewed by 2456

Abstract

Movement disorders are increasingly being recognized as a manifestation of childhood-onset mitochondrial diseases (MDs). However, the spectrum and characteristics of these conditions have not been studied in detail in the context of a well-defined cohort of patients. We retrospectively explored a cohort of [...] Read more.

Movement disorders are increasingly being recognized as a manifestation of childhood-onset mitochondrial diseases (MDs). However, the spectrum and characteristics of these conditions have not been studied in detail in the context of a well-defined cohort of patients. We retrospectively explored a cohort of individuals with childhood-onset MDs querying the Nationwide Italian Collaborative Network of Mitochondrial Diseases database. Using a customized online questionnaire, we attempted to collect data from the subgroup of patients with movement disorders. Complete information was available for 102 patients. Movement disorder was the presenting feature of MD in 45 individuals, with a mean age at onset of 11 years. Ataxia was the most common movement disorder at onset, followed by dystonia, tremor, hypokinetic disorders, chorea, and myoclonus. During the disease course, most patients (67.7%) encountered a worsening of their movement disorder. Basal ganglia involvement, cerebral white matter changes, and cerebellar atrophy were the most commonly associated neuroradiological patterns. Forty-one patients harbored point mutations in the mitochondrial DNA, 10 carried mitochondrial DNA rearrangements, and 41 cases presented mutations in nuclear-DNA-encoded genes, the latter being associated with an earlier onset and a higher impairment in activities of daily living. Among our patients, 32 individuals received pharmacological treatment; clonazepam and oral baclofen were the most commonly used drugs, whereas levodopa and intrathecal baclofen administration were the most effective. A better delineation of the movement disorders phenotypes starting in childhood may improve our diagnostic workup in MDs, fine tuning management, and treatment of affected patients. Full article

(This article belongs to the Special Issue Mitochondrial Disorders: Molecular, Clinical and Therapeutic Advances)

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16 pages, 10807 KiB

Open AccessArticle

Endothelial Nitric Oxide Synthase Knockdown in Human Stem Cells Impacts Mitochondrial Biogenesis and Adipogenesis: Live-Cell Real-Time Fluorescence Imaging

by Sylvia Lee-Huang, Philip Lin Huang and Paul Lee Huang

J. Clin. Med. 2021, 10(4), 631; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10040631 - 7 Feb 2021

Cited by 5 | Viewed by 3982

Abstract

We carried out live-cell real-time fluorescence imaging to follow the effects of genetic (siRNA) knockdown (KD) of endothelial nitric oxide synthase (eNOS) on mitochondrial biogenesis and adipogenesis in human mesenchymal stem cells (hMSCs). We report here that eNOS KD in hMSCs blocks mitochondrial [...] Read more.

We carried out live-cell real-time fluorescence imaging to follow the effects of genetic (siRNA) knockdown (KD) of endothelial nitric oxide synthase (eNOS) on mitochondrial biogenesis and adipogenesis in human mesenchymal stem cells (hMSCs). We report here that eNOS KD in hMSCs blocks mitochondrial biogenesis and adipogenesis. The transfer of mitochondria from normal hMSCs to eNOS-deficient hMSCs restores adipogenesis. Furthermore, cell-free mitochondria purified from normal hMSCs also restores adipogenesis in eNOS-deficient cells. Thus, eNOS and NO signaling are essential for mitochondrial biogenesis, and mitochondrial activity is indispensable for adipogenesis in hMSC differentiation. We mapped the path and identified the mechanisms of mitochondrial transfer. We captured real-time images of differentiated mature adipocytes in mitosis and replication. These results reveal that human stem cell-differentiated fat cells are capable of replication. This new finding offers novel insights into our understanding of fat cell expansion and the development of obesity. Real-time imaging in live cells allows synchronized investigation of mitochondrial biogenesis and adipogenesis in stem cell differentiation without reducing living cells to nonliving samples for functional analysis. Live-cell real-time imaging can thus be a faithful and immediate tool for molecular diagnostic medicine. Furthermore, our results suggest that mitochondrial remodeling can be a useful approach in treating adiposity, diabetes, and abnormalities in energy metabolism and vascular signaling. Full article

(This article belongs to the Special Issue Mitochondrial Disorders: Molecular, Clinical and Therapeutic Advances)

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15 pages, 638 KiB

Open AccessArticle

Rapid Whole-Exome Sequencing as a Diagnostic Tool in a Neonatal/Pediatric Intensive Care Unit

by Robert Śmigiel, Mateusz Biela, Krzysztof Szmyd, Michal Błoch, Elżbieta Szmida, Paweł Skiba, Anna Walczak, Piotr Gasperowicz, Joanna Kosińska, Małgorzata Rydzanicz, Piotr Stawiński, Anna Biernacka, Marzena Zielińska, Waldemar Gołębiowski, Agnieszka Jalowska, Grażyna Ohia, Bożena Głowska, Wojciech Walas, Barbara Królak-Olejnik, Paweł Krajewski, Jolanta Sykut-Cegielska, Maria M. Sąsiadek and Rafał Płoski Show full author list Hide full author list

J. Clin. Med. 2020, 9(7), 2220; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9072220 - 13 Jul 2020

Cited by 49 | Viewed by 3812

Abstract

Genetic disorders are the leading cause of infant morbidity and mortality. Due to the large number of genetic diseases, molecular and phenotype heterogeneity and often severe course, these diseases remain undiagnosed. In infants with a suspected acute monogenic disease, rapid whole-exome sequencing (R-WES) [...] Read more.

Genetic disorders are the leading cause of infant morbidity and mortality. Due to the large number of genetic diseases, molecular and phenotype heterogeneity and often severe course, these diseases remain undiagnosed. In infants with a suspected acute monogenic disease, rapid whole-exome sequencing (R-WES) can be successfully performed. R-WES (singletons) was performed in 18 unrelated infants with a severe and/or progressing disease with the suspicion of genetic origin hospitalized in an Intensive Care Unit (ICU). Blood samples were also collected from the parents. The results from the R-WES were available after 5–14 days. A conclusive genetic diagnosis was obtained in 13 children, corresponding to an overall diagnostic yield of 72.2%. For nine patients, R-WES was used as a first-tier test. Eight patients were diagnosed with inborn errors of metabolism, mainly mitochondrial diseases. In two patients, the disease was possibly caused by variants in genes which so far have not been associated with human disease (NARS1 and DCAF5). R-WES proved to be an effective diagnostic tool for critically ill infants in ICUs suspected of having a genetic disorder. It also should be considered as a first-tier test after precise clinical description. The quickly obtained diagnosis impacts patient’s medical management, and families can receive genetic counseling. Full article

(This article belongs to the Special Issue Mitochondrial Disorders: Molecular, Clinical and Therapeutic Advances)

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Review

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27 pages, 4764 KiB

Open AccessEditor’s ChoiceReview

Molecular Genetics Overview of Primary Mitochondrial Myopathies

by Ignazio Giuseppe Arena, Alessia Pugliese, Sara Volta, Antonio Toscano and Olimpia Musumeci

J. Clin. Med. 2022, 11(3), 632; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11030632 - 26 Jan 2022

Cited by 14 | Viewed by 6356

Abstract

Mitochondrial disorders are the most common inherited conditions, characterized by defects in oxidative phosphorylation and caused by mutations in nuclear or mitochondrial genes. Due to its high energy request, skeletal muscle is typically involved. According to the International Workshop of Experts in Mitochondrial [...] Read more.

Mitochondrial disorders are the most common inherited conditions, characterized by defects in oxidative phosphorylation and caused by mutations in nuclear or mitochondrial genes. Due to its high energy request, skeletal muscle is typically involved. According to the International Workshop of Experts in Mitochondrial Diseases held in Rome in 2016, the term Primary Mitochondrial Myopathy (PMM) should refer to those mitochondrial disorders affecting principally, but not exclusively, the skeletal muscle. The clinical presentation may include general isolated myopathy with muscle weakness, exercise intolerance, chronic ophthalmoplegia/ophthalmoparesis (cPEO) and eyelids ptosis, or multisystem conditions where there is a coexistence with extramuscular signs and symptoms. In recent years, new therapeutic targets have been identified leading to the launch of some promising clinical trials that have mainly focused on treating muscle symptoms and that require populations with defined genotype. Advantages in next-generation sequencing techniques have substantially improved diagnosis. So far, an increasing number of mutations have been identified as responsible for mitochondrial disorders. In this review, we focused on the principal molecular genetic alterations in PMM. Accordingly, we carried out a comprehensive review of the literature and briefly discussed the possible approaches which could guide the clinician to a genetic diagnosis. Full article

(This article belongs to the Special Issue Mitochondrial Disorders: Molecular, Clinical and Therapeutic Advances)

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19 pages, 1753 KiB

Open AccessReview

Exercise Testing, Physical Training and Fatigue in Patients with Mitochondrial Myopathy Related to mtDNA Mutations

by Tina D. Jeppesen, Karen L. Madsen, Nanna S. Poulsen, Nicoline Løkken and John Vissing

J. Clin. Med. 2021, 10(8), 1796; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10081796 - 20 Apr 2021

Cited by 7 | Viewed by 2931

Abstract

Mutations in mitochondrial DNA (mtDNA) cause disruption of the oxidative phosphorylation chain and impair energy production in cells throughout the human body. Primary mitochondrial disorders due to mtDNA mutations can present with symptoms from adult-onset mono-organ affection to death in infancy due to [...] Read more.

Mutations in mitochondrial DNA (mtDNA) cause disruption of the oxidative phosphorylation chain and impair energy production in cells throughout the human body. Primary mitochondrial disorders due to mtDNA mutations can present with symptoms from adult-onset mono-organ affection to death in infancy due to multi-organ involvement. The heterogeneous phenotypes that patients with a mutation of mtDNA can present with are thought, at least to some extent, to be a result of differences in mtDNA mutation load among patients and even among tissues in the individual. The most common symptom in patients with mitochondrial myopathy (MM) is exercise intolerance. Since mitochondrial function can be assessed directly in skeletal muscle, exercise studies can be used to elucidate the physiological consequences of defective mitochondria due to mtDNA mutations. Moreover, exercise tests have been developed for diagnostic purposes for mitochondrial myopathy. In this review, we present the rationale for exercise testing of patients with MM due to mutations in mtDNA, evaluate the diagnostic yield of exercise tests for MM and touch upon how exercise tests can be used as tools for follow-up to assess disease course or effects of treatment interventions. Full article

(This article belongs to the Special Issue Mitochondrial Disorders: Molecular, Clinical and Therapeutic Advances)

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18 pages, 14371 KiB

Open AccessReview

Mitochondrial Syndromes Revisited

by Daniele Orsucci, Elena Caldarazzo Ienco, Andrea Rossi, Gabriele Siciliano and Michelangelo Mancuso

J. Clin. Med. 2021, 10(6), 1249; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10061249 - 17 Mar 2021

Cited by 28 | Viewed by 3859

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Mitochondrial Disorders: Molecular, Clinical and Therapeutic Advances)

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16 pages, 310 KiB

Open AccessReview

Therapeutical Management and Drug Safety in Mitochondrial Diseases—Update 2020

by Francesco Gruosso, Vincenzo Montano, Costanza Simoncini, Gabriele Siciliano and Michelangelo Mancuso

J. Clin. Med. 2021, 10(1), 94; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10010094 - 29 Dec 2020

Cited by 7 | Viewed by 3056

Abstract

Mitochondrial diseases (MDs) are a group of genetic disorders that may manifest with vast clinical heterogeneity in childhood or adulthood. These diseases are characterized by dysfunctional mitochondria and oxidative phosphorylation deficiency. Patients are usually treated with supportive and symptomatic therapies due to the [...] Read more.

Mitochondrial diseases (MDs) are a group of genetic disorders that may manifest with vast clinical heterogeneity in childhood or adulthood. These diseases are characterized by dysfunctional mitochondria and oxidative phosphorylation deficiency. Patients are usually treated with supportive and symptomatic therapies due to the absence of a specific disease-modifying therapy. Management of patients with MDs is based on different therapeutical strategies, particularly the early treatment of organ-specific complications and the avoidance of catabolic stressors or toxic medication. In this review, we discuss the therapeutic management of MDs, supported by a revision of the literature, and provide an overview of the drugs that should be either avoided or carefully used both for the specific treatment of MDs and for the management of comorbidities these subjects may manifest. We finally discuss the latest therapies approved for the management of MDs and some ongoing clinical trials. Full article

(This article belongs to the Special Issue Mitochondrial Disorders: Molecular, Clinical and Therapeutic Advances)

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