Details of Disease

Disease Name

MELAS syndrome

mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes; MELAS; MELAS syndrome; mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes; mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes; mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes; mitochondrial encephalomyopathy, lactic acidosis and stroke

Definition

MELAS (Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke) syndrome is a rare progressive multisystemic disorder characterized by encephalomyopathy, lactic acidosis, and stroke-like episodes. Other features include endocrinopathy, heart disease, diabetes, hearing loss, and neurological and psychiatric manifestations.

Disease Hierarchy

DIS6SVEE: Syndromic disease

DISA6PTN: Mitochondrial encephalomyopathy

DIS81Z3S: MELAS syndrome

Disease Identifiers

MONDO ID

MONDO_0010789

MESH ID

D017241

UMLS CUI

C0162671

OMIM ID

540000

MedGen ID

56485

Orphanet ID

550

SNOMED CT ID

39925003

General Information of Disease (ID: DIS81Z3S)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 7 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
SOD1	TTP9K3Q	moderate	Biomarker	[1]
ABL2	TT1A6HL	Strong	Genetic Variation	[2]
IL1A	TTPM6HI	Strong	Biomarker	[3]
MAPKAP1	TTWDKCL	Strong	Genetic Variation	[4]
MRM2	TTUQ7WN	Strong	Biomarker	[5]
PRSS1	TT2WR1T	Strong	Genetic Variation	[6]
SLC25A4	TTU5A6Q	Strong	Altered Expression	[7]
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⏷ Show the Full List of 7 DTT(s)

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
ASNS	DEXISVQ	Strong	Biomarker	[8]
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This Disease Is Related to 23 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ND5	OT45LW1K	Limited	Genetic Variation	[9]
ND6	OTG47B7B	Limited	Genetic Variation	[10]
MT-CO1	OTG3O9BN	Supportive	Mitochondrial	[11]
MT-ND1	OTCLGIXV	Supportive	Mitochondrial	[12]
ATP6	OTPHOGLX	Strong	CausalMutation	[13]
CALB1	OTM7IXDG	Strong	Altered Expression	[14]
COQ8A	OT1ETSA2	Strong	Genetic Variation	[15]
COX2	OTTMVBJJ	Strong	GermlineCausalMutation	[16]
COX3	OTNNGBYJ	Strong	Genetic Variation	[17]
CYTB	OTAHB98A	Strong	Genetic Variation	[18]
FASTKD2	OTD635WX	Strong	Genetic Variation	[19]
GFM2	OT51TIMY	Strong	Genetic Variation	[20]
GLIS3	OTBC960E	Strong	Genetic Variation	[21]
MTERF1	OT3EIK39	Strong	Genetic Variation	[22]
ND3	OT1OC3K3	Strong	Genetic Variation	[23]
ND4	OT4RQVAA	Strong	Genetic Variation	[24]
NDUFA1	OTKBUQXP	Strong	Genetic Variation	[25]
NDUFV1	OTEVK4WW	Strong	Genetic Variation	[26]
PRPF6	OT3U0ABN	Strong	Altered Expression	[7]
RARS2	OT3WLAD8	Strong	Genetic Variation	[27]
RERE	OT3G4GBZ	Strong	Genetic Variation	[2]
TOMM20	OT76TPR2	Strong	Biomarker	[28]
TRMU	OTJ1KXM7	Strong	Altered Expression	[29]
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⏷ Show the Full List of 23 DOT(s)

References

1	Antioxidant agents have a different expression pattern in muscle fibers of patients with mitochondrial diseases.Acta Neuropathol. 2002 Mar;103(3):215-20. doi: 10.1007/s004010100455. Epub 2001 Nov 16.
2	Molecular epidemiology of childhood mitochondrial encephalomyopathies in a Finnish population: sequence analysis of entire mtDNA of 17 children reveals heteroplasmic mutations in tRNAArg, tRNAGlu, and tRNALeu(UUR) genes.Pediatrics. 2004 Aug;114(2):443-50. doi: 10.1542/peds.114.2.443.
3	Cytokine expression in the muscle of HIV-infected patients: evidence for interleukin-1 alpha accumulation in mitochondria of AZT fibers. Ann Neurol. 1994 Nov;36(5):752-8. doi: 10.1002/ana.410360511.
4	Effects of nitric oxide donors on cybrids harbouring the mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) A3243G mitochondrial DNA mutation.Biochem J. 2005 Oct 15;391(Pt 2):191-202. doi: 10.1042/BJ20050272.
5	Defective mitochondrial rRNA methyltransferase MRM2 causes MELAS-like clinical syndrome.Hum Mol Genet. 2017 Nov 1;26(21):4257-4266. doi: 10.1093/hmg/ddx314.
6	Application of molecular imaging combined with genetic screening in diagnosing MELAS, diabetes and recurrent pancreatitis.Folia Neuropathol. 2016;54(1):66-71. doi: 10.5114/fn.2016.58917.
7	Mitochondrial DNA expression in mitochondrial myopathies and coordinated expression of nuclear genes involved in ATP production.J Biol Chem. 1993 Jun 5;268(16):12156-63.
8	CHOP (C/EBP homologous protein) and ASNS (asparagine synthetase) induction in cybrid cells harboring MELAS and NARP mitochondrial DNA mutations. Mitochondrion. 2007 Feb-Apr;7(1-2):80-8.
9	A novel mutation in the mitochondrial MT-ND5 gene in a family with MELAS. The relevance of genetic analysis on targeted tissues.Mitochondrion. 2020 Jan;50:14-18. doi: 10.1016/j.mito.2019.10.001. Epub 2019 Oct 19.
10	An mtDNA mutation, 14453G-->A, in the NADH dehydrogenase subunit 6 associated with severe MELAS syndrome.Eur J Hum Genet. 2001 Oct;9(10):805-9. doi: 10.1038/sj.ejhg.5200712.
11	MELAS-like encephalomyopathy caused by a new pathogenic mutation in the mitochondrial DNA encoded cytochrome c oxidase subunit I. Neuromuscul Disord. 2012 Nov;22(11):990-4. doi: 10.1016/j.nmd.2012.06.003. Epub 2012 Jul 23.
12	LHON/MELAS overlap syndrome associated with a mitochondrial MTND1 gene mutation. Eur J Hum Genet. 2005 May;13(5):623-7. doi: 10.1038/sj.ejhg.5201363.
13	Defective mitochondrial ATPase due to rare mtDNA m.8969G>A mutation-causing lactic acidosis, intellectual disability, and poor growth.Neurogenetics. 2018 Jan;19(1):49-53. doi: 10.1007/s10048-018-0537-9. Epub 2018 Jan 19.
14	Decreased hippocampal expression of calbindin D28K and cognitive impairment in MELAS.J Neurol Sci. 2012 Jun 15;317(1-2):29-34. doi: 10.1016/j.jns.2012.03.005. Epub 2012 Apr 5.
15	Movement disorders in mitochondrial diseases.Rev Neurol (Paris). 2016 Aug-Sep;172(8-9):524-529. doi: 10.1016/j.neurol.2016.07.003. Epub 2016 Jul 28.
16	Isolated cytochrome c oxidase deficiency as a cause of MELAS.J Med Genet. 2008 Feb;45(2):117-21. doi: 10.1136/jmg.2007.052076.
17	A MELAS syndrome family harboring two mutations in mitochondrial genome.Exp Mol Med. 2008 Jun 30;40(3):354-60. doi: 10.3858/emm.2008.40.3.354.
18	A 4-base pair deletion in the mitochondrial cytochrome b gene associated with parkinsonism/MELAS overlap syndrome.Ann Neurol. 1999 Jan;45(1):130-3. doi: 10.1002/1531-8249(199901)45:1<130::aid-art21>3.3.co;2-q.
19	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.
20	The A3243G tRNALeu(UUR) MELAS mutation causes amino acid misincorporation and a combined respiratory chain assembly defect partially suppressed by overexpression of EFTu and EFG2.Hum Mol Genet. 2008 Dec 1;17(23):3697-707. doi: 10.1093/hmg/ddn265. Epub 2008 Aug 27.
21	LHON/MELAS overlap mutation in ND1 subunit of mitochondrial complex I affects ubiquinone binding as revealed by modeling in Escherichia coli NDH-1.Biochim Biophys Acta. 2012 Feb;1817(2):312-8. doi: 10.1016/j.bbabio.2011.10.014. Epub 2011 Nov 4.
22	A novel point mutation in the mitochondrial tRNA(Leu)(UUR) gene in a family with mitochondrial myopathy.Ann Neurol. 1992 Jun;31(6):672-5. doi: 10.1002/ana.410310617.
23	Transition from Leigh syndrome to MELAS syndrome in a patient with heteroplasmic MT-ND3 m.10158T>C.Brain Dev. 2019 Oct;41(9):803-807. doi: 10.1016/j.braindev.2019.05.006. Epub 2019 Jun 6.
24	A new disease-related mutation for mitochondrial encephalopathy lactic acidosis and strokelike episodes (MELAS) syndrome affects the ND4 subunit of the respiratory complex I.Am J Hum Genet. 1992 Sep;51(3):457-68.
25	The MELAS mutations 3946 and 3949 perturb the critical structure in a conserved loop of the ND1 subunit of mitochondrial complex I.Hum Mol Genet. 2006 Sep 1;15(17):2543-52. doi: 10.1093/hmg/ddl176. Epub 2006 Jul 18.
26	Outcome of epilepsy in patients with mitochondrial disorders: Phenotype genotype and magnetic resonance imaging correlations.Clin Neurol Neurosurg. 2018 Jan;164:182-189. doi: 10.1016/j.clineuro.2017.12.010. Epub 2017 Dec 9.
27	Mitochondrial disease and epilepsy.Dev Med Child Neurol. 2012 May;54(5):397-406. doi: 10.1111/j.1469-8749.2011.04214.x. Epub 2012 Jan 28.
28	Increased number of mitochondria in capillaries distributed in stroke-like lesions of two patients with MELAS.Neuropathology. 2019 Oct;39(5):404-410. doi: 10.1111/neup.12593. Epub 2019 Aug 13.
29	The 2-thiouridylase function of the human MTU1 (TRMU) enzyme is dispensable for mitochondrial translation.Hum Mol Genet. 2011 Dec 1;20(23):4634-43. doi: 10.1093/hmg/ddr397. Epub 2011 Sep 1.