Details of Disease

Disease Name

Mitochondrial encephalomyopathy

Definition

A heterogenous group of disorders characterized by alterations of mitochondrial metabolism that result in muscle and nervous system dysfunction. These are often multisystemic and vary considerably in age at onset (usually in the first or second decade of life), distribution of affected muscles, severity, and course. (From Adams et al., Principles of Neurology, 6th ed, pp984-5)

Disease Hierarchy

DIS9SA7V: Mitochondrial myopathy

DISA6PTN: Mitochondrial encephalomyopathy

Disease Identifiers

MONDO ID

MONDO_0004675

MESH ID

D017237

UMLS CUI

C0162666

MedGen ID

57960

SNOMED CT ID

447292006

General Information of Disease (ID: DISA6PTN)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 2 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ABL2	TT1A6HL	Strong	Genetic Variation	[1]
NTF4	TTIM2WO	Strong	Altered Expression	[2]
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This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC25A42	DTU4HKJ	Limited	Biomarker	[3]
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This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
NDUFS2	DEKX5CD	Definitive	Biomarker	[4]
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This Disease Is Related to 31 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
AIPL1	OT4VBD78	Limited	Biomarker	[5]
FASTKD2	OTD635WX	Limited	Genetic Variation	[6]
MRPS25	OTN7IISS	Limited	Autosomal recessive	[7]
MTFMT	OT1OIVJL	Limited	CausalMutation	[8]
PRPF8	OTU39JZI	Limited	Genetic Variation	[5]
SCO2	OTJQQDRS	Limited	Biomarker	[9]
TMEM65	OT2JUZ7Q	Limited	Genetic Variation	[10]
AARS2	OTOB0KSG	Strong	Genetic Variation	[11]
ACAD9	OT4HITJ6	Strong	Genetic Variation	[12]
AIFM1	OTKPWB7Q	Strong	Genetic Variation	[13]
ATP6	OTPHOGLX	Strong	Genetic Variation	[14]
COQ4	OTIU7FAZ	Strong	Genetic Variation	[15]
CYTB	OTAHB98A	Strong	Genetic Variation	[16]
DNM1L	OTXK1Q1G	Strong	Biomarker	[17]
FBXL4	OTZECCIQ	Strong	Genetic Variation	[18]
FOXRED1	OTYEB8YK	Strong	Biomarker	[19]
ND5	OT45LW1K	Strong	Genetic Variation	[20]
NDUFA1	OTKBUQXP	Strong	Genetic Variation	[21]
NDUFB11	OTFG5777	Strong	Biomarker	[21]
NDUFS4	OTJKUYEE	Strong	Biomarker	[22]
RARS2	OT3WLAD8	Strong	Genetic Variation	[23]
RERE	OT3G4GBZ	Strong	Genetic Variation	[1]
RNASEH1	OTT7L25X	Strong	Genetic Variation	[24]
SUCLA2	OTMZD4PW	Strong	Genetic Variation	[25]
SUCLG1	OTDCSPXH	Strong	Genetic Variation	[26]
TARS2	OTXQY23P	Strong	Genetic Variation	[27]
TK2	OTS1V4XB	Strong	Genetic Variation	[28]
TMEM70	OTLTKYXG	Strong	Biomarker	[29]
TTC19	OTQ0QH1P	Strong	Genetic Variation	[30]
NDUFAF4	OTWJ5B9M	Definitive	Genetic Variation	[31]
NDUFV2	OTSZF7D6	Definitive	Biomarker	[4]
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⏷ Show the Full List of 31 DOT(s)

References

1	A novel mitochondrial tRNA Arg mutation resulting in an anticodon swap in a patient with mitochondrial encephalomyopathy.Eur J Hum Genet. 2013 May;21(5):571-3. doi: 10.1038/ejhg.2012.153. Epub 2012 Jul 11.
2	Neurotrophin-4 is up-regulated in ragged-red fibers associated with pathogenic mitochondrial DNA mutations.Ann Neurol. 1998 Apr;43(4):536-40. doi: 10.1002/ana.410430421.
3	Expanding the phenotype of SLC25A42-associated mitochondrial encephalomyopathy.Clin Genet. 2018 May;93(5):1097-1102. doi: 10.1111/cge.13210. Epub 2018 Mar 25.
4	Mutant NDUFS3 subunit of mitochondrial complex I causes Leigh syndrome. J Med Genet. 2004 Jan;41(1):14-7. doi: 10.1136/jmg.2003.014316.
5	Histopathologic-genotypic correlations in retinitis pigmentosa and allied diseases.Ophthalmic Genet. 2005 Jun;26(2):91-100. doi: 10.1080/13816810590968032.
6	Identification of FASTKD2 compound heterozygous mutations as the underlying cause of autosomal recessive MELAS-like syndrome.Mitochondrion. 2017 Jul;35:54-58. doi: 10.1016/j.mito.2017.05.005. Epub 2017 May 9.
7	MRPS25 mutations impair mitochondrial translation and cause encephalomyopathy. Hum Mol Genet. 2019 Aug 15;28(16):2711-2719. doi: 10.1093/hmg/ddz093.
8	Phenotypic spectrum of eleven patients and five novel MTFMT mutations identified by exome sequencing and candidate gene screening.Mol Genet Metab. 2014 Mar;111(3):342-352. doi: 10.1016/j.ymgme.2013.12.010. Epub 2013 Dec 25.
9	COX19 mediates the transduction of a mitochondrial redox signal from SCO1 that regulates ATP7A-mediated cellular copper efflux.Mol Biol Cell. 2013 Mar;24(6):683-91. doi: 10.1091/mbc.E12-09-0705. Epub 2013 Jan 23.
10	A mutation in the TMEM65 gene results in mitochondrial myopathy with severe neurological manifestations.Eur J Hum Genet. 2017 Jun;25(6):744-751. doi: 10.1038/ejhg.2017.20. Epub 2017 Mar 15.
11	AARS2 leukoencephalopathy: A new variant of mitochondrial encephalomyopathy.Mol Genet Genomic Med. 2019 Apr;7(4):e00582. doi: 10.1002/mgg3.582. Epub 2019 Jan 31.
12	Mitochondrial encephalomyopathy due to a novel mutation in ACAD9.JAMA Neurol. 2013 Sep 1;70(9):1177-9. doi: 10.1001/jamaneurol.2013.3197.
13	Mutations in AIFM1 cause an X-linked childhood cerebellar ataxia partially responsive to riboflavin.Eur J Paediatr Neurol. 2018 Jan;22(1):93-101. doi: 10.1016/j.ejpn.2017.09.004. Epub 2017 Sep 15.
14	The biochemical characterization of a missense mutation m.8914C>T in ATP6 gene associated with mitochondrial encephalomyopathy.Int J Dev Neurosci. 2018 Dec;71:172-174. doi: 10.1016/j.ijdevneu.2018.09.007. Epub 2018 Sep 28.
15	Mutations in COQ4, an essential component of coenzyme Q biosynthesis, cause lethal neonatal mitochondrial encephalomyopathy.J Med Genet. 2015 Sep;52(9):627-35. doi: 10.1136/jmedgenet-2015-103140. Epub 2015 Jul 16.
16	Mitochondrial encephalomyopathy and complex III deficiency associated with a stop-codon mutation in the cytochrome b gene.Am J Hum Genet. 2000 Dec;67(6):1400-10. doi: 10.1086/316900. Epub 2000 Oct 20.
17	A lethal defect of mitochondrial and peroxisomal fission. N Engl J Med. 2007 Apr 26;356(17):1736-41. doi: 10.1056/NEJMoa064436.
18	Mutations in FBXL4, encoding a mitochondrial protein, cause early-onset mitochondrial encephalomyopathy.Am J Hum Genet. 2013 Sep 5;93(3):482-95. doi: 10.1016/j.ajhg.2013.07.016. Epub 2013 Aug 29.
19	FOXRED1, encoding an FAD-dependent oxidoreductase complex-I-specific molecular chaperone, is mutated in infantile-onset mitochondrial encephalopathy. Hum Mol Genet. 2010 Dec 15;19(24):4837-47. doi: 10.1093/hmg/ddq414. Epub 2010 Sep 21.
20	Clinical and Neuroimaging Features in Two Children with Mutations in the Mitochondrial ND5 Gene.Neuropediatrics. 2015 Aug;46(4):277-81. doi: 10.1055/s-0035-1550149. Epub 2015 May 14.
21	X-linked NDUFA1 gene mutations associated with mitochondrial encephalomyopathy. Ann Neurol. 2007 Jan;61(1):73-83. doi: 10.1002/ana.21036.
22	Mitochondrial complex III stabilizes complex I in the absence of NDUFS4 to provide partial activity.Hum Mol Genet. 2012 Jan 1;21(1):115-20. doi: 10.1093/hmg/ddr446. Epub 2011 Sep 28.
23	Cerebellar hypoplasia and brainstem thinning associated with severe white matter and basal ganglia abnormalities in a child with an mtDNA deletion.J Inherit Metab Dis. 2011 Dec;34(6):1225-7. doi: 10.1007/s10545-011-9376-7. Epub 2011 Aug 9.
24	RNASEH1 Mutations Impair mtDNA Replication and Cause Adult-Onset Mitochondrial Encephalomyopathy. Am J Hum Genet. 2015 Jul 2;97(1):186-93. doi: 10.1016/j.ajhg.2015.05.013. Epub 2015 Jun 18.
25	Mitochondrial encephalomyopathy with elevated methylmalonic acid is caused by SUCLA2 mutations. Brain. 2007 Mar;130(Pt 3):853-61. doi: 10.1093/brain/awl383. Epub 2007 Feb 7.
26	Clinical, Molecular, and Computational Analysis in two cases with mitochondrial encephalomyopathy associated with SUCLG1 mutation in a consanguineous family.Biochem Biophys Res Commun. 2018 Jan 8;495(2):1730-1737. doi: 10.1016/j.bbrc.2017.12.011. Epub 2017 Dec 5.
27	A Human Disease-causing Point Mutation in Mitochondrial Threonyl-tRNA Synthetase Induces Both Structural and Functional Defects.J Biol Chem. 2016 Mar 18;291(12):6507-20. doi: 10.1074/jbc.M115.700849. Epub 2016 Jan 25.
28	Transcriptomic profiling of TK2 deficient human skeletal muscle suggests a role for the p53 signalling pathway and identifies growth and differentiation factor-15 as a potential novel biomarker for mitochondrial myopathies.BMC Genomics. 2014 Feb 1;15:91. doi: 10.1186/1471-2164-15-91.
29	TMEM70 mutations cause isolated ATP synthase deficiency and neonatal mitochondrial encephalocardiomyopathy. Nat Genet. 2008 Nov;40(11):1288-90. doi: 10.1038/ng.246. Epub 2008 Oct 26.
30	Novel TTC19 mutation in a family with severe psychiatric manifestations and complex III deficiency.Neurogenetics. 2013 May;14(2):153-60. doi: 10.1007/s10048-013-0361-1. Epub 2013 Mar 28.
31	C6ORF66 is an assembly factor of mitochondrial complex I. Am J Hum Genet. 2008 Jan;82(1):32-8. doi: 10.1016/j.ajhg.2007.08.003.