Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Neurology
Published in: BMC Neurology 1/2020

01-12-2020 | Electroencephalography | Case report

Late-onset MELAS syndrome with mtDNA 14453G→A mutation masquerading as an acute encephalitis: a case report

Authors: Yuki Yokota, Makoto Hara, Takayoshi Akimoto, Tomotaka Mizoguchi, Yu-ichi Goto, Ichizo Nishino, Satoshi Kamei, Hideto Nakajima

Published in: BMC Neurology | Issue 1/2020

Login to get access

Abstract

Background

A unique patient with MELAS syndrome, who initially masqueraded as having acute encephalitis and was eventually diagnosed with MELAS syndrome harboring a mtDNA 14453G → A mutation, is described.

Case presentation

A 74-year-old Japanese man was admitted to another hospital due to acute onset of cognitive impairment and psychosis. After 7 days he was transferred to our hospital with seizures and deteriorating psychosis. The results of primary ancillary tests that included EEG, CSF findings, and brain MRI supported the diagnosis of an acute encephalitis. HSV-DNA and antibodies against neuronal surface antigens in the CSF were all negative. With the assistance of the lactate peak on the brain lesions in the magnetic resonance spectroscopy image and genetic analysis of the biopsied muscle, he was eventually diagnosed with MELAS syndrome harboring mtDNA 14453G → A mutation in the ND6 gene.

Conclusions

This case provides a caveat that MELAS syndrome can manifest in the symptoms and ancillary tests masquerading as an acute encephalitis caused by infection or autoimmunity. This is the first adult patient seen to harbor the mtDNA14453G → A with a unique onset, which broadens the phenotypic spectrum of MELAS syndrome associated with ND6 gene mutation.
Appendix
Available only for authorised users
Literature
1.
Pavlakis SG, Phillips PC, DiMauro S, De Vivo DC, Rowland LP. Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes: a distinctive clinical syndrome. Ann Neurol. 1984;16:481–8.CrossRef
2.
Goto Y, Horai S, Matsuoka T, et al. Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS): a correlative study of the clinical features and mitochondrial DNA mutation. Neurology. 1992;42:545–50.CrossRef
3.
Alston CL, Rocha MC, Lax NZ, Turnbull DM, Taylor RW. The genetics and pathology of mitochondrial disease. J Pathol. 2017;241:236–50.CrossRef
4.
MITOMAP: A human mitochondrial genome database. http://​mitomaphtml/​mitomaphtml.​
5.
Deschauer M, Tennant S, Rokicka A, et al. MELAS associated with mutations in the POLG1 gene. Neurology. 2007;68:1741–2.CrossRef
6.
Goto Y, Nonaka I, Horai S. A mutation in the tRNA (Leu)(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. Nature. 1990;348:651–3.CrossRef
7.
Fassone E, Rahman S. Complex I deficiency: clinical features, biochemistry and molecular genetics. J Med Genet. 2012;49:578–90.CrossRef
8.
Ravn K, Wibrand F, Hansen FJ, et al. An mtDNA mutation, 14453G-->a, in the NADH dehydrogenase subunit 6 associated with severe MELAS syndrome. Eur J Hum Genet. 2001;9:805–9.CrossRef
9.
Leonard JV, Schapira AH. Mitochondrial respiratory chain disorders I: mitochondrial DNA defects. Lancet. 2000;355:299–304.CrossRef
10.
Venkatesan A, Tunkel AR, Bloch KC, et al. Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium. Clin Infect Dis. 2013;57:1114–28.CrossRef
11.
Johns DR, Stein AG, Wityk R. MELAS syndrome masquerading as herpes simplex encephalitis. Neurology. 1993;43:2471–3.CrossRef
12.
Sharfstein SR, Gordon MF, Libman RB, Malkin ES. Adult-onset MELAS presenting as herpes encephalitis. Arch Neurol. 1999;56:241–3.CrossRef
13.
Hsu YC, Yang FC, Perng CL, et al. Adult-onset of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome presenting as acute meningoencephalitis: a case report. J Emerg Med. 2012;43:e163–6.CrossRef
14.
Gieraerts C, Demaerel P, Van Damme P, Wilms G. Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome mimicking herpes simplex encephalitis on imaging studies. J Comput Assist Tomogr. 2013;37:279–81.CrossRef
15.
Gooriah R, Dafalla BE, Venugopalan TC. Led astray: MELAS initially misdiagnosed as herpes simplex encephalitis. Acta Neurol Belg. 2015;115:789–92.CrossRef
16.
Caldarazzo Ienco E, Orsucci D, Simoncini C, et al. Acute encephalopathy of the temporal lobes leading to m.3243A>G. when MELAS is not always MELAS. Mitochondrion. 2016;30:148–50.CrossRef
17.
Ciafaloni E, Ricci E, Shanske S, et al. MELAS: clinical features, biochemistry, and molecular genetics. Ann Neurol. 1992;31:391–8.CrossRef
18.
Graus F, Titulaer MJ, Balu R, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016;15:391–404.CrossRef
19.
Jun AS, Trounce IA, Brown MD, Shoffner JM, Wallace DC. Use of transmitochondrial cybrids to assign a complex I defect to the mitochondrial DNA-encoded NADH dehydrogenase subunit 6 gene mutation at nucleotide pair 14459 that causes Leber hereditary optic neuropathy and dystonia. Mol Cell Biol. 1996;16:771–7.CrossRef
20.
Caporali L, Iommarini L, La Morgia C, et al. Peculiar combinations of individually non-pathogenic missense mitochondrial DNA variants cause low penetrance Leber's hereditary optic neuropathy. PLoS Genet. 2018;14:e1007210.CrossRef
21.
Zhadanov SI, Atamanov VV, Zhadanov NI, et al. A novel mtDNA ND6 gene mutation associated with LHON in a Caucasian family. Biochem Biophys Res Commun. 2005;332:1115–21.CrossRef
22.
Howell N, Oostra RJ, Bolhuis PA, et al. Sequence analysis of the mitochondrial genomes from Dutch pedigrees with Leber hereditary optic neuropathy. Am J Hum Genet. 2003;72:1460–9.CrossRef
23.
Jun AS, Brown MD, Wallace DC. A mitochondrial DNA mutation at nucleotide pair 14459 of the NADH dehydrogenase subunit 6 gene associated with maternally inherited Leber hereditary optic neuropathy and dystonia. Proc Natl Acad Sci U S A. 1994;91:6206–10.CrossRef
24.
Valentino ML, Avoni P, Barboni P, et al. Mitochondrial DNA nucleotide changes C14482G and C14482A in the ND6 gene are pathogenic for Leber's hereditary optic neuropathy. Ann Neurol. 2002;51:774–8.CrossRef
25.
Howell N, Bogolin C, Jamieson R, Marenda DR, Mackey DA. mtDNA mutations that cause optic neuropathy: how do we know? Am J Hum Genet. 1998;62:196–202.CrossRef
26.
Johns DR, Neufeld MJ, Park RD. An ND-6 mitochondrial DNA mutation associated with Leber hereditary optic neuropathy. Biochem Biophys Res Commun. 1992;187:1551–7.CrossRef
27.
Ugalde C, Triepels RH, Coenen MJ, et al. Impaired complex I assembly in a Leigh syndrome patient with a novel missense mutation in the ND6 gene. Ann Neurol. 2003;54:665–9.CrossRef
28.
Chinnery PF, Brown DT, Andrews RM, et al. The mitochondrial ND6 gene is a hot spot for mutations that cause Leber’s hereditary optic neuropathy. Brain. 2001;124:209–18.CrossRef
29.
Leo-Kottler B, Christ-Adler M, Baumann B, Zrenner E, Wissinger B. Leber's hereditary optic neuropathy: clinical and molecular genetic results obtained in a family with a new point mutation at nucleotide position 14498 in the ND 6 gene. Ger J Ophthalmol. 1996;5:233–40.PubMed
30.
Qian Y, Zhou X, Hu Y, et al. Clinical evaluation and mitochondrial DNA sequence analysis in three Chinese families with Leber's hereditary optic neuropathy. Biochem Biophys Res Commun. 2005;332:614–21.CrossRef
31.
Wissinger B, Besch D, Baumann B, et al. Mutation analysis of the ND6 gene in patients with Lebers hereditary optic neuropathy. Biochem Biophys Res Commun. 1997;234:511–5.CrossRef
32.
De Vries DD, Went LN, Bruyn GW, et al. Genetic and biochemical impairment of mitochondrial complex I activity in a family with Leber hereditary optic neuropathy and hereditary spastic dystonia. Am J Hum Genet. 1996;58:703–11.PubMedPubMedCentral
33.
Malfatti E, Bugiani M, Invernizzi F, et al. Novel mutations of ND genes in complex I deficiency associated with mitochondrial encephalopathy. Brain. 2007;130:1894–904.CrossRef
34.
Miyabayashi S, Hanamizu H, Nakamura R, Endo H, Tada K. Defects of mitochondrial respiratory enzymes in cloned cells from MELAS fibroblasts. J Inherit Metab Dis. 1992;15:797–802.CrossRef
35.
Ng YS, Lax NZ, Maddison P, et al. MT-ND5 mutation exhibits highly variable neurological manifestations at low mutant load. EBioMedicine. 2018;30:86–93.CrossRef
36.
Lukyanova LD, Kirova YI. Mitochondria-controlled signaling mechanisms of brain protection in hypoxia. Front Neurosci. 2015;9:320.CrossRef
37.
Mariotti C, Savarese N, Suomalainen A, et al. Genotype to phenotype correlations in mitochondrial encephalomyopathies associated with the A3243G mutation of mitochondrial DNA. J Neurol. 1995;242:304–12.CrossRef
38.
Macmillan C, Lach B, Shoubridge EA. Variable distribution of mutant mitochondrial DNAs (tRNA (Leu [3243])) in tissues of symptomatic relatives with MELAS: the role of mitotic segregation. Neurology. 1993;43:1586–90.CrossRef
39.
Yokota M, Hatakeyama H, Okabe S, Ono Y, Goto Y. Mitochondrial respiratory dysfunction caused by a heteroplasmic mitochondrial DNA mutation blocks cellular reprogramming. Hum Mol Genet. 2015;24:4698–709.CrossRef
40.
Chang DD, Clayton DA. Priming of human mitochondrial DNA replication occurs at the light-strand promoter. Proc Natl Acad Sci U S A. 1985;82:351–5.CrossRef
41.
Wang Q, Ito M, Adams K, et al. Mitochondrial DNA control region sequence variation in migraine headache and cyclic vomiting syndrome. Am J Med Genet A. 2004;131:50–8.CrossRef
Metadata
Title
Late-onset MELAS syndrome with mtDNA 14453G→A mutation masquerading as an acute encephalitis: a case report
Authors
Yuki Yokota
Makoto Hara
Takayoshi Akimoto
Tomotaka Mizoguchi
Yu-ichi Goto
Ichizo Nishino
Satoshi Kamei
Hideto Nakajima
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2020
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-020-01818-w

Other articles of this Issue 1/2020

BMC Neurology 1/2020 Go to the issue

Research article

Risk factors affecting the 1-year outcomes of minor ischemic stroke: results from Xi’an stroke registry study of China

Research article

Increased incidence of Susac syndrome: a case series study

Case report

Symptomatic hemiparkinsonism due to extensive middle and posterior fossa arachnoid cyst: case report

Research article

Correlations of apathy with clinical symptoms of Alzheimer’s disease and olfactory dysfunctions: a cross-sectional study

Case report

Bilateral thalamic lesions in a patient with probable acute disseminating encephalomyelitis: a case report

Case report

Wallerian degeneration of bilateral cerebral peduncles after acute carbon monoxide poisoning