Mitochondrial Chronic Progressive External Ophthalmoplegia

Overview

Journal Brain Sci

Publisher MDPI

Date 2024 Feb 23

PMID 38391710

Authors

Ali Ali

Ali Esmaeil

Raed Behbehani

Affiliations

Soon will be listed here.

Abstract

Background: Chronic progressive external ophthalmoplegia (CPEO) is a rare disorder that can be at the forefront of several mitochondrial diseases. This review overviews mitochondrial CPEO encephalomyopathies to enhance accurate recognition and diagnosis for proper management.

Methods: This study is conducted based on publications and guidelines obtained by selective review in PubMed. Randomized, double-blind, placebo-controlled trials, Cochrane reviews, and literature meta-analyses were particularly sought.

Discussion: CPEO is a common presentation of mitochondrial encephalomyopathies, which can result from alterations in mitochondrial or nuclear DNA. Genetic sequencing is the gold standard for diagnosing mitochondrial encephalomyopathies, preceded by non-invasive tests such as fibroblast growth factor-21 and growth differentiation factor-15. More invasive options include a muscle biopsy, which can be carried out after uncertain diagnostic testing. No definitive treatment option is available for mitochondrial diseases, and management is mainly focused on lifestyle risk modification and supplementation to reduce mitochondrial load and symptomatic relief, such as ptosis repair in the case of CPEO. Nevertheless, various clinical trials and endeavors are still at large for achieving beneficial therapeutic outcomes for mitochondrial encephalomyopathies.

Key Messages: Understanding the varying presentations and genetic aspects of mitochondrial CPEO is crucial for accurate diagnosis and management.

References

Cardaioli E, Da Pozzo P, Malfatti E, Battisti C, Gallus G, Gaudiano C . A second MNGIE patient without typical mitochondrial skeletal muscle involvement. Neurol Sci. 2010; 31(4):491-4. DOI: 10.1007/s10072-010-0225-5. View

Greaves L, Yu-Wai-Man P, Blakely E, Krishnan K, Beadle N, Kerin J . Mitochondrial DNA defects and selective extraocular muscle involvement in CPEO. Invest Ophthalmol Vis Sci. 2010; 51(7):3340-6. PMC: 2904000. DOI: 10.1167/iovs.09-4659. View

Jacinto S, Guerreiro P, de Oliveira R, Cunha-Oliveira T, Santos M, Grazina M . MPV17 Mutations Are Associated With a Quiescent Energetic Metabolic Profile. Front Cell Neurosci. 2021; 15:641264. PMC: 8011494. DOI: 10.3389/fncel.2021.641264. View

Alonzo J, Venkataraman C, Field M, Stover P . The mitochondrial inner membrane protein MPV17 prevents uracil accumulation in mitochondrial DNA. J Biol Chem. 2018; 293(52):20285-20294. PMC: 6311524. DOI: 10.1074/jbc.RA118.004788. View

Esmaeil A, Ali A, Behbehani R . Leber's hereditary optic neuropathy: Update on current diagnosis and treatment. Front Ophthalmol (Lausanne). 2024; 2:1077395. PMC: 11182214. DOI: 10.3389/fopht.2022.1077395. View

Ardissone A, Bruno C, Diodato D, Donati A, Ghezzi D, Lamantea E . Clinical, imaging, biochemical and molecular features in Leigh syndrome: a study from the Italian network of mitochondrial diseases. Orphanet J Rare Dis. 2021; 16(1):413. PMC: 8501644. DOI: 10.1186/s13023-021-02029-3. View

Ying Y, Liang Y, Luo X, Wei M . Case Report: Clinical and Genetic Characteristics of Pearson Syndrome in a Chinese Boy and 139 Patients. Front Genet. 2022; 13:802402. PMC: 9168460. DOI: 10.3389/fgene.2022.802402. View

Zelissen R, Ahmadian S, Montilla-Rojo J, Timmer E, Ummelen M, Hopman A . Fusion of Wild-Type Mesoangioblasts with Myotubes of mtDNA Mutation Carriers Leads to a Proportional Reduction in mtDNA Mutation Load. Int J Mol Sci. 2023; 24(3). PMC: 9917062. DOI: 10.3390/ijms24032679. View

Caporali L, Bello L, Tagliavini F, La Morgia C, Maresca A, Di Vito L . DGUOK recessive mutations in patients with CPEO, mitochondrial myopathy, parkinsonism and mtDNA deletions. Brain. 2017; 141(1):e3. DOI: 10.1093/brain/awx301. View

10.

Erdinc D, Rodriguez-Luis A, Fassad M, Mackenzie S, Watson C, Valenzuela S . Pathological variants in TOP3A cause distinct disorders of mitochondrial and nuclear genome stability. EMBO Mol Med. 2023; 15(5):e16775. PMC: 10165364. DOI: 10.15252/emmm.202216775. View

11.

Sommerville E, Dalla Rosa I, Rosenberg M, Bruni F, Thompson K, Rocha M . Identification of a novel heterozygous guanosine monophosphate reductase (GMPR) variant in a patient with a late-onset disorder of mitochondrial DNA maintenance. Clin Genet. 2019; 97(2):276-286. PMC: 7004030. DOI: 10.1111/cge.13652. View

12.

Mani S, Rao S, Kumar M . Genetic heterogeneity of mitochondrial genome in thiamine deficient Leigh syndrome patients. J Neurol Sci. 2019; 404:91-100. DOI: 10.1016/j.jns.2019.07.007. View

13.

Szczesny R, Hejnowicz M, Steczkiewicz K, Muszewska A, Borowski L, Ginalski K . Identification of a novel human mitochondrial endo-/exonuclease Ddk1/c20orf72 necessary for maintenance of proper 7S DNA levels. Nucleic Acids Res. 2013; 41(5):3144-61. PMC: 3597694. DOI: 10.1093/nar/gkt029. View

14.

Halter J, Michael W, Schupbach M, Mandel H, Casali C, Orchard K . Allogeneic haematopoietic stem cell transplantation for mitochondrial neurogastrointestinal encephalomyopathy. Brain. 2015; 138(Pt 10):2847-58. PMC: 4836400. DOI: 10.1093/brain/awv226. View

15.

Kang Y, Wang Y, Zhang Q, Pang X, Gu W . A case of hypopituitarism accompanying Kearns-Sayre syndrome treated with human chorionic gonadotropin: A case report and literature review. Andrologia. 2016; 49(8). DOI: 10.1111/and.12711. View

16.

Alves C, Teixeira S, Martin-Saavedra J, Goncalves F, Lo Russo F, Muraresku C . Pediatric Leigh Syndrome: Neuroimaging Features and Genetic Correlations. Ann Neurol. 2020; 88(2):218-232. DOI: 10.1002/ana.25789. View

17.

Shaibani A, Shchelochkov O, Zhang S, Katsonis P, Lichtarge O, Wong L . Mitochondrial neurogastrointestinal encephalopathy due to mutations in RRM2B. Arch Neurol. 2009; 66(8):1028-32. PMC: 2747647. DOI: 10.1001/archneurol.2009.139. View

18.

Bernier F, Boneh A, Dennett X, Chow C, Cleary M, Thorburn D . Diagnostic criteria for respiratory chain disorders in adults and children. Neurology. 2002; 59(9):1406-11. DOI: 10.1212/01.wnl.0000033795.17156.00. View

19.

Ronchi D, Caporali L, Manenti G, Meneri M, Mohamed S, Bordoni A . Variants Result in Late-Onset Mitochondrial Myopathy With Altered Muscle Mitochondrial DNA Homeostasis. Front Genet. 2020; 11:860. PMC: 7419576. DOI: 10.3389/fgene.2020.00860. View

20.

Ciesielski G, Rosado-Ruiz F, Kaguni L . Purification and Comparative Assay of Human Mitochondrial Single-Stranded DNA-Binding Protein. Methods Mol Biol. 2015; 1351:211-22. PMC: 4703105. DOI: 10.1007/978-1-4939-3040-1_16. View