دورية أكاديمية
أعرض في EDS

Mitochondrial myopathies diagnosed in adulthood: clinico-genetic spectrum and long-term outcomes.

التفاصيل البيبلوغرافية
العنوان: Mitochondrial myopathies diagnosed in adulthood: clinico-genetic spectrum and long-term outcomes.
المؤلفون: Beecher G; Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.; Division of Neurology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada T6G 2G3., Gavrilova RH; Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.; Department of Clinical Genomics, Mayo Clinic, Rochester, MN 55905, USA., Mandrekar J; Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA., Naddaf E; Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.
المصدر: Brain communications [Brain Commun] 2024 Feb 14; Vol. 6 (2), pp. fcae041. Date of Electronic Publication: 2024 Feb 14 (Print Publication: 2024).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 101755125 Publication Model: eCollection Cited Medium: Internet ISSN: 2632-1297 (Electronic) Linking ISSN: 26321297 NLM ISO Abbreviation: Brain Commun Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [Oxford] : Oxford University Press, [2019]-
مستخلص: Mitochondrial myopathies are frequently recognized in childhood as part of a broader multisystem disorder and often overlooked in adulthood. Herein, we describe the phenotypic and genotypic spectrum and long-term outcomes of mitochondrial myopathies diagnosed in adulthood, focusing on neuromuscular features, electrodiagnostic and myopathological findings and survival. We performed a retrospective chart review of adult patients diagnosed with mitochondrial myopathy at Mayo Clinic (2005-21). We identified 94 patients. Median time from symptom onset to diagnosis was 11 years (interquartile range 4-21 years). Median age at diagnosis was 48 years (32-63 years). Primary genetic defects were identified in mitochondrial DNA in 48 patients (10 with single large deletion, 38 with point mutations) and nuclear DNA in 29. Five patients had multiple mitochondrial DNA deletions or depletion without nuclear DNA variants. Twelve patients had histopathological features of mitochondrial myopathy without molecular diagnosis. The most common phenotypes included multisystem disorder ( n = 30); mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (14); limb myopathy (13); chronic progressive external ophthalmoplegia (12); and chronic progressive external ophthalmoplegia-plus (12). Isolated skeletal muscle manifestations occurred in 27%. Sixty-nine per cent had CNS and 21% had cardiac involvement. Mutations most frequently involved MT-TL1 (27) and POLG (17); however, a wide spectrum of established and novel molecular defects, with overlapping phenotypes, was identified. Electrodiagnostic studies identified myopathy (77%), fibrillation potentials (27%) and axonal peripheral neuropathy (42%, most common with nuclear DNA variants). Among 42 muscle biopsies available, median percentage counts were highest for cytochrome C oxidase negative fibres (5.1%) then ragged blue (1.4%) and ragged red fibres (0.5%). Skeletal muscle weakness was mild and slowly progressive (decline in strength summated score of 0.01/year). Median time to gait assistance was 5.5 years from diagnosis and 17 years from symptom onset. Thirty patients died, with median survival of 33.4 years from symptom onset and 10.9 years from diagnosis. Median age at death was 55 years. Cardiac involvement was associated with increased mortality [hazard ratio 2.36 (1.05, 5.29)]. There was no difference in survival based on genotype or phenotype. Despite the wide phenotypic and genotypic spectrum, mitochondrial myopathies in adults share similar features with slowly progressive limb weakness, contrasting with common multiorgan involvement and high mortality.
Competing Interests: The authors report no competing interests.
(© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)
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فهرسة مساهمة: Keywords: MELAS; POLG; chronic progressive external ophthalmoplegia; inherited myopathies; mitochondrial myopathies
تواريخ الأحداث: Date Created: 20240304 Latest Revision: 20240305
رمز التحديث: 20240305
مُعرف محوري في PubMed: PMC10906953
DOI: 10.1093/braincomms/fcae041
PMID: 38434220
قاعدة البيانات: MEDLINE
الوصف
تدمد:2632-1297
DOI:10.1093/braincomms/fcae041