دورية أكاديمية
Mitochondrial myopathies diagnosed in adulthood: clinico-genetic spectrum and long-term outcomes.
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.) |
References: | Neurology. 2002 Nov 12;59(9):1406-11. (PMID: 12427892) Brain. 2014 Dec;137(Pt 12):3200-12. (PMID: 25281868) Neurology. 2020 Nov 17;95(20):933-938. (PMID: 33046616) Nat Rev Genet. 2012 Dec;13(12):878-90. (PMID: 23154810) Neuromuscul Disord. 2016 Apr-May;26(4-5):272-6. (PMID: 27020842) Mitochondrion. 2015 Jan;20:82-94. (PMID: 25526677) J Neurol Sci. 1990 Dec;100(1-2):63-9. (PMID: 1965208) Acta Neurol Scand. 1995 Apr;91(4):287-93. (PMID: 7625156) Neurology. 2022 Aug 16;99(7):e730-e742. (PMID: 35641312) Science. 1988 Dec 9;242(4884):1427-30. (PMID: 3201231) Neurology. 1997 Jul;49(1):239-45. (PMID: 9222196) Neuropathology. 2015 Apr;35(2):130-6. (PMID: 25378026) Neuromuscul Disord. 1995 Sep;5(5):399-413. (PMID: 7496174) Nat Rev Neurol. 2013 Aug;9(8):429-44. (PMID: 23835535) J Neurol. 2015 May;262(5):1301-9. (PMID: 25808502) Mitochondrion. 2017 Jan;32:27-30. (PMID: 27856367) J Neurol. 2017 Aug;264(8):1777-1784. (PMID: 28695364) JIMD Rep. 2016;26:103-13. (PMID: 26354038) Muscle Nerve. 1995 Jul;18(7):753-60. (PMID: 7783765) Am J Hum Genet. 1997 Feb;60(2):373-80. (PMID: 9012410) Muscle Nerve. 2001 Feb;24(2):170-91. (PMID: 11180201) Exp Mol Med. 2010 Jun 30;42(6):446-55. (PMID: 20440095) Brain. 1986 Oct;109 ( Pt 5):915-38. (PMID: 3779373) Muscle Nerve. 2008 Mar;37(3):293-9. (PMID: 18067134) Mitochondrion. 2021 Jan;56:52-61. (PMID: 33220502) Am J Hum Genet. 2010 Jul 9;87(1):52-9. (PMID: 20598274) J Neuropathol Exp Neurol. 2019 Jun 1;78(6):508-514. (PMID: 31100146) Neurol Sci. 2012 Apr;33(2):449-52. (PMID: 21751099) J Clin Med. 2022 Jan 26;11(3):. (PMID: 35160083) Neuromuscul Disord. 2012 Dec;22 Suppl 3:S226-9. (PMID: 23182644) Clin Neurophysiol. 1999 Jul;110(7):1284-9. (PMID: 10423194) N Engl J Med. 1989 May 18;320(20):1293-9. (PMID: 2541333) J Neurol. 2022 Dec;269(12):6555-6565. (PMID: 35980466) Pediatr Neurol. 2018 Mar;80:8-23. (PMID: 29449072) Neurol Genet. 2018 Mar 26;4(2):e230. (PMID: 29600276) N Engl J Med. 1999 Sep 30;341(14):1037-44. (PMID: 10502593) Can J Neurol Sci. 2011 Jan;38(1):119-23. (PMID: 21156440) Nature. 1988 Feb 25;331(6158):717-9. (PMID: 2830540) Neuromuscul Disord. 2005 Apr;15(4):276-86. (PMID: 15792866) Eur J Neurol. 2016 Jun;23(6):1020-7. (PMID: 26822221) Lancet Neurol. 2021 Jul;20(7):573-584. (PMID: 34146515) Int J Cardiol. 2021 Oct 15;341:48-55. (PMID: 34298071) Neuromuscul Disord. 1992;2(2):125-35. (PMID: 1422200) Muscle Nerve. 2003 Dec;28(6):757-9. (PMID: 14639592) Muscle Nerve. 2011 Jun;43(6):795-800. (PMID: 21607963) Stroke. 1988 May;19(5):604-7. (PMID: 3363593) Neuromuscul Disord. 2021 Oct;31(10):978-987. (PMID: 34736635) Neurol Clin Pract. 2021 Apr;11(2):97-104. (PMID: 33842062) Neurology. 1991 Nov;41(11):1822-8. (PMID: 1682853) Muscle Nerve. 1991 Jan;14(1):35-41. (PMID: 1846937) J Inherit Metab Dis. 2020 May;43(3):459-466. (PMID: 31652339) Genet Med. 2015 Sep;17(9):689-701. (PMID: 25503498) Neurol Genet. 2020 Mar 02;6(2):e402. (PMID: 32337332) J Neurol Neurosurg Psychiatry. 2013 Aug;84(8):936-8. (PMID: 23355809) |
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 |
تدمد: | 2632-1297 |
---|---|
DOI: | 10.1093/braincomms/fcae041 |