Ischemic optic neuropathy as first presentation in patient with m.3243 A > G MELAS classic mutation

BMC Neurology

Case Report

Daniela Piga¹  Francesca Magri²  Claudia Mainetti²  Alessandra Govoni³  Daniele Velardo³  Delia Gagliardi⁴  Megi Meneri⁴  Simone Scarcella⁴  Stefania Corti⁴  Giacomo Pietro Comi⁵  Dario Ronchi⁵  Valeria Minorini⁶  Laura Dell’Arti⁶ 

[1] Neurology Unit, Foundation IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy;Neuromuscular and Rare Diseases Unit, Department of Neuroscience, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, 20122, Milan, Italy;Neuroscience Section, Dino Ferrari Centre, Department of Pathophysiology and Transplantation (DEPT), University of Milan, Via Francesco Sforza 35, 20122, Milan, Italy;Neuroscience Section, Dino Ferrari Centre, Department of Pathophysiology and Transplantation (DEPT), University of Milan, Via Francesco Sforza 35, 20122, Milan, Italy;Neurology Unit, Foundation IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy;Neuroscience Section, Dino Ferrari Centre, Department of Pathophysiology and Transplantation (DEPT), University of Milan, Via Francesco Sforza 35, 20122, Milan, Italy;Neuromuscular and Rare Diseases Unit, Department of Neuroscience, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, 20122, Milan, Italy;Ophthalmological Unit, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan, Italy;

关键词: Optic neuropathy;    Mitochondrial disease;    MELAS;    Stroke-like episodes;    NAION;   

DOI  :  10.1186/s12883-023-03198-3

 received in 2022-10-17, accepted in 2023-03-22,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundMitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a systemic disorder in which multi-organ dysfunction may occur from mitochondrial metabolism failure. Maternally inherited mutations in the MT-TL1 gene are the most frequent causes for this disorder. Clinical manifestations may include stroke-like episodes, epilepsy, dementia, headache and myopathy. Among these, acute visual failure, usually in association with cortical blindness, can occur because of stroke-like episodes affecting the occipital cortex or the visual pathways. Vision loss due to optic neuropathy is otherwise considered a typical manifestation of other mitochondrial diseases such as Leber hereditary optic neuropathy (LHON).Case presentationHere we describe a 55-year-old woman, sister of a previously described patient with MELAS harbouring the m.3243A > G (p.0, MT-TL1) mutation, with otherwise unremarkable medical history, that presented with subacute, painful visual impairment of one eye, accompanied by proximal muscular pain and headache. Over the next weeks, she developed severe and progressive vision loss limited to one eye. Ocular examination confirmed unilateral swelling of the optic nerve head; fluorescein angiography showed segmental perfusion delay in the optic disc and papillary leakage. Neuroimaging, blood and CSF examination and temporal artery biopsy ruled out neuroinflammatory disorders and giant cell arteritis (GCA). Mitochondrial sequencing analysis confirmed the m.3243A > G transition, and excluded the three most common LHON mutations, as well as the m.3376G > A LHON/MELAS overlap syndrome mutation. Based on the constellation of clinical symptoms and signs presented in our patient, including the muscular involvement, and the results of the investigations, the diagnosis of optic neuropathy as a stroke-like event affecting the optic disc was performed. L-arginine and ubidecarenone therapies were started with the aim to improve stroke-like episode symptoms and prevention. The visual defect remained stable with no further progression or outbreak of new symptoms.ConclusionsAtypical clinical presentations must be always considered in mitochondrial disorders, even in well-described phenotypes and when mutational load in peripheral tissue is low. Mitotic segregation of mitochondrial DNA (mtDNA) does not allow to know the exact degree of heteroplasmy existent within different tissue, such as retina and optic nerve. Important therapeutic implications arise from a correct diagnosis of atypical presentation of mitochondrial disorders.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023. corrected publication 2023

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