Details of Disease

General Information of Disease (ID: DISWQU45)

• Disease Name: Leigh syndrome
• Synonyms: Leigh's necrotizing encephalopathy; Leigh syndrome due to mitochondrial Complex 3 deficiency; necrotizing encephalopathy, infantile Subacute, of Leigh; Leigh syndrome due to mitochondrial Complex 4 deficiency; SNE; Leigh syndrome due to mitochondrial Complex 2 deficiency; subacute necrotizing encephalomyelopathy; subacute necrotizing encephalopathy; Leigh syndrome due to mitochondrial Complex 1 deficiency; Leigh syndrome due to mitochondrial Complex 5 deficiency; Leigh's disease; Leigh syndrome spectrum; Leigh disease; LSS; infantile necrotizing encephalomyelopathy; infantile subacute necrotizing encephalopathy; juvenile subacute necrotizing encephalomyelopathy; LS; Leigh syndrome
• Disease Class: 5C53: Inborn energy metabolism error
• Definition: A progressive neurological disease defined by specific neuropathological features associating brainstem and basal ganglia lesions.
• Disease Hierarchy:
  DISSYRHC: Hereditary peripheral neuropathy
  DISK7IP8: Mitochondrial oxidative phosphorylation disorder
  DISWQU45: Leigh syndrome
• ICD Code:
  ICD-11: ICD-11: 5C53.24
  ICD-10: ICD-10: G31.8
  Expand ICD-11: '5C53.24
  Expand ICD-10: 'G31.8
• Disease Identifiers:
  MONDO ID: MONDO_0009723
  MESH ID: D007888
  UMLS CUI: C0023264
  OMIM ID: 256000
  MedGen ID: 44095
  Orphanet ID: 506
  SNOMED CT ID: 29570005

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 2 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
BioE-743	DM7PT8R	Phase 2	NA	[1]
Coenzyme Q10 analog	DMO0VGH	Phase 2	NA	[2]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 130 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
UQCRQ	OTLQNJC7	Limited	Autosomal recessive	[3]
VPS13D	OTI2PG1E	Limited	Autosomal recessive	[3]
ADAR	OTQNOHR8	Limited	Autosomal recessive	[3]
CLPB	OT1I0IBK	Limited	Autosomal recessive	[3]
COQ9	OTM2T1FI	Limited	Autosomal recessive	[3]
COX3	OTNNGBYJ	Limited	Genetic Variation	[5]
COX4I1	OTU0FC24	Limited	Autosomal recessive	[3]
COX8A	OTU0NR39	Limited	Autosomal recessive	[3]
CYTB	OTAHB98A	Limited	CausalMutation	[18]
DNM1L	OTXK1Q1G	Limited	Autosomal recessive	[3]
IARS2	OTDX4SCA	Limited	Autosomal recessive	[3]
LIAS	OTOSW67J	Limited	Autosomal recessive	[3]
LONP1	OT665WYT	Limited	Autosomal recessive	[3]
MORC2	OT52A8BJ	Limited	Autosomal dominant	[3]
MT-CO1	OTG3O9BN	Limited	Mitochondrial	[3]
NARS2	OTL5X535	Limited	Autosomal recessive	[3]
NAXE	OTRZPISQ	Limited	Autosomal recessive	[3]
ND3	OT1OC3K3	Limited	Genetic Variation	[19]
ND5	OT45LW1K	Limited	Genetic Variation	[20]
ND6	OTG47B7B	Limited	Genetic Variation	[21]
NDUFA12	OTCD6I5M	Limited	Autosomal recessive	[3]
NDUFA4	OTDVH3QG	Limited	Autosomal recessive	[3]
NDUFAF4	OTWJ5B9M	Limited	Autosomal recessive	[3]
NDUFV2	OTSZF7D6	Limited	Autosomal recessive	[3]
PET117	OT76T8O0	Limited	Autosomal recessive	[3]
POLG	OTDUCT04	Limited	Autosomal recessive	[3]
PTCD3	OTHTOLE0	Limited	Autosomal recessive	[3]
RANBP2	OTFG5CVF	Limited	Autosomal dominant	[3]
RNASEH1	OTT7L25X	Limited	Autosomal recessive	[3]
SDHAF1	OTDG5VW7	Limited	Autosomal recessive	[3]
SLC25A19	OT157TY3	Limited	Autosomal recessive	[3]
SLC25A4	OTKYLK2J	Limited	Autosomal dominant	[3]
SLC25A46	OTFEV9SV	Limited	Autosomal recessive	[3]
SLC39A8	OT6C6MNV	Limited	Autosomal recessive	[3]
SQOR	OTTLD0KB	Limited	Autosomal recessive	[3]
SRSF2	OTVDHO6U	Limited	Genetic Variation	[22]
SSBP1	OTH2PZWH	Limited	Autosomal dominant	[3]
TARS2	OTXQY23P	Limited	Autosomal recessive	[3]
TIMMDC1	OTIK4I5R	Limited	Autosomal recessive	[3]
NUP62	OTMN63DH	Disputed	Autosomal recessive	[3]
AIFM1	OTKPWB7Q	Moderate	X-linked	[3]
ATP5MK	OTS656HO	Moderate	Autosomal recessive	[3]
BTD	OTJYTQ69	Moderate	Autosomal recessive	[3]
CDSN	OTQW4HV6	moderate	Biomarker	[23]
CUTC	OTOVHLU9	moderate	Genetic Variation	[24]
DLAT	OT9LBJVN	Moderate	Autosomal recessive	[3]
FARS2	OTXAK6F0	Moderate	Autosomal recessive	[3]
FOXRED1	OTYEB8YK	Moderate	Autosomal recessive	[3]
GFM1	OTUN4V3N	Moderate	Autosomal recessive	[3]
GFM2	OT51TIMY	Moderate	Autosomal recessive	[3]
GTPBP3	OTU52TXX	Moderate	Autosomal recessive	[3]
HPDL	OTW7D1SV	Moderate	Autosomal recessive	[3]
LIPT1	OT2KCI00	Moderate	Autosomal recessive	[3]
MECR	OTJQ5XKQ	Moderate	Autosomal recessive	[3]
MFF	OTEVIXOM	Moderate	Autosomal recessive	[3]
MRPS34	OT7P9V67	Moderate	Autosomal recessive	[3]
NDUFA1	OTKBUQXP	Moderate	X-linked	[3]
NDUFA13	OT0UOKIT	Moderate	Autosomal recessive	[3]
NDUFA2	OTNSTATK	Moderate	Autosomal recessive	[3]
NDUFA9	OTMKQJJ8	Moderate	Autosomal recessive	[3]
NDUFAF8	OT9EVJYG	Moderate	Autosomal recessive	[3]
NDUFB8	OTW4A4Q0	Moderate	Autosomal recessive	[3]
NDUFC2	OT9M119L	Moderate	Autosomal recessive	[3]
NDUFS3	OTX61TQQ	Moderate	Autosomal recessive	[3]
NDUFS7	OTIRMB2O	Moderate	Autosomal recessive	[3]
NDUFS8	OTMEAWKO	Moderate	Autosomal recessive	[3]
NUBPL	OTQMCSXT	Moderate	Autosomal recessive	[3]
OPA1	OTJGNWPW	Moderate	Autosomal recessive	[3]
PDHB	OT2NHE5E	Moderate	Autosomal recessive	[3]
PDSS2	OTEOQBMX	Moderate	Autosomal recessive	[3]
PET100	OTQ0J3DT	Moderate	Autosomal recessive	[3]
PNPT1	OTBR2Q0F	Moderate	Autosomal recessive	[3]
SUCLG1	OTDCSPXH	Moderate	Autosomal recessive	[3]
TACO1	OTK1WUBL	Moderate	Autosomal recessive	[3]
TBPL1	OT4I143E	moderate	Genetic Variation	[5]
TPK1	OTCHPUD0	Moderate	Autosomal recessive	[3]
TRMU	OTJ1KXM7	Moderate	Autosomal recessive	[3]
TSFM	OTP6OKPJ	Moderate	Autosomal recessive	[3]
ATP11A	OT7M9ZDK	Strong	Genetic Variation	[25]
ATP5PF	OTDAE8FP	Strong	Genetic Variation	[26]
ATP6	OTPHOGLX	Strong	Genetic Variation	[27]
ATP8	OTYQQR53	Strong	Biomarker	[28]
BCS1L	OT5PY5CY	Strong	Autosomal recessive	[29]
C19orf12	OTVSJ1AR	Strong	Genetic Variation	[30]
COQ4	OTIU7FAZ	Strong	Genetic Variation	[31]
COQ8A	OT1ETSA2	Strong	Genetic Variation	[30]
COX5A	OTP0961M	Strong	Genetic Variation	[20]
CPOX	OTIAY121	Strong	Genetic Variation	[20]
EMC3	OTY2H39E	Strong	Biomarker	[32]
FARP2	OTNRQIMK	Strong	Biomarker	[33]
GYG2	OTAJ7YEW	Strong	Genetic Variation	[34]
LAMA2	OTFROQWE	Strong	Biomarker	[35]
MTO1	OT7HCZ1D	Strong	Genetic Variation	[36]
ND2	OTG9OHOX	Strong	Genetic Variation	[37]
ND4	OT4RQVAA	Strong	Genetic Variation	[38]
NDUFA10	OTBURQ3A	Strong	Autosomal recessive	[39]
NDUFA5	OTR848KZ	Strong	Genetic Variation	[40]
NDUFAF3	OT4MCB6W	Strong	Genetic Variation	[41]
NDUFS6	OT9IOONQ	Strong	Genetic Variation	[42]
PANK2	OTFBW889	Strong	Genetic Variation	[30]
PARL	OT7DMHSA	Strong	Biomarker	[43]
PDP1	OT82RTMT	Strong	Biomarker	[8]
COX10	OTCYIS0L	Definitive	Autosomal recessive	[44]
COX15	OTUIYHIW	Definitive	Autosomal recessive	[39]
DLD	OT378CU9	Definitive	Autosomal recessive	[3]
EARS2	OTNCJKY7	Definitive	Autosomal recessive	[3]
ECHS1	OTS0593S	Definitive	Autosomal recessive	[3]
ETHE1	OTP9A2BQ	Definitive	Autosomal recessive	[3]
FBXL4	OTZECCIQ	Definitive	Autosomal recessive	[3]
HIBCH	OTU2VHWR	Definitive	Autosomal recessive	[3]
LRPPRC	OTXSK5LP	Definitive	Autosomal recessive	[3]
MT-ND1	OTCLGIXV	Definitive	Mitochondrial	[3]
MTFMT	OT1OIVJL	Definitive	Autosomal recessive	[3]
MTRFR	OTG2GU7J	Definitive	Autosomal recessive	[3]
NDUFAF2	OTC8QPRS	Definitive	Autosomal recessive	[3]
NDUFAF5	OTN5V274	Definitive	Autosomal recessive	[3]
NDUFAF6	OTRJMIGT	Definitive	Autosomal recessive	[3]
NDUFS1	OTTIZDFR	Definitive	Autosomal recessive	[3]
NDUFS2	OTBT8KW9	Definitive	Autosomal recessive	[3]
NDUFS4	OTJKUYEE	Definitive	Autosomal recessive	[3]
NDUFV1	OTEVK4WW	Definitive	Autosomal recessive	[3]
PDHA1	OTGEU8IK	Definitive	X-linked	[3]
PDHX	OTG7O271	Definitive	Autosomal recessive	[3]
SCO2	OTJQQDRS	Definitive	Autosomal recessive	[3]
SDHA	OTOJ8QFF	Definitive	Autosomal recessive	[39]
SERAC1	OTWH1ULQ	Definitive	Autosomal recessive	[3]
SLC19A3	OTOWP1CT	Definitive	Autosomal recessive	[3]
SUCLA2	OTMZD4PW	Definitive	Autosomal recessive	[3]
SURF1	OTAINRSS	Definitive	Autosomal recessive	[3]
TTC19	OTQ0QH1P	Definitive	Autosomal recessive	[3]

This Disease Is Related to 13 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
LONP1	TTM1VPZ	Limited	Autosomal recessive	[3]
NDUFA13	TTRU1NG	Moderate	Autosomal recessive	[3]
NDUFAF2	TTCHGVF	moderate	Biomarker	[4]
OPA1	TTTU49Q	Moderate	Autosomal recessive	[3]
TYRP1	TTFRV98	moderate	Genetic Variation	[5]
CRAT	TTC8M31	Strong	Genetic Variation	[6]
NPTX2	TTNJ5A6	Strong	Biomarker	[7]
OGDH	TTH8T6I	Strong	Biomarker	[8]
PGD	TTZ3IFB	Strong	Genetic Variation	[9]
TFPI	TT068JH	Strong	Genetic Variation	[10]
TKT	TT04R7I	Strong	Altered Expression	[11]
NDUFAF2	TTCHGVF	Definitive	Autosomal recessive	[3]
SLC19A3	TT9BTWM	Definitive	Genetic Variation	[12]

This Disease Is Related to 6 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC25A19	DTT82QK	Limited	Autosomal recessive	[3]
SLC25A19	DTT82QK	Limited	Biomarker	[12]
SLC25A4	DTPTFKU	Limited	Autosomal dominant	[3]
SLC39A8	DTLPQGT	Limited	Autosomal recessive	[3]
SLC39A8	DTLPQGT	Strong	Genetic Variation	[13]
SLC19A3	DT39CEA	Definitive	Autosomal recessive	[3]

This Disease Is Related to 8 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
FARS2	DE0WGR8	Moderate	Autosomal recessive	[3]
FARS2	DE0WGR8	moderate	Biomarker	[14]
NDUFS3	DE741FI	Moderate	Autosomal recessive	[3]
NDUFS3	DE741FI	moderate	Genetic Variation	[15]
NDUFS7	DEIW03B	Moderate	Autosomal recessive	[3]
NDUFS7	DEIW03B	moderate	Biomarker	[16]
NDUFS2	DEKX5CD	Strong	Biomarker	[17]
NDUFS2	DEKX5CD	Definitive	Autosomal recessive	[3]

References

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• [9] PGD for the m.14487 T>C mitochondrial DNA mutation resulted in the birth of a healthy boy.Hum Reprod. 2017 Mar 1;32(3):698-703. doi: 10.1093/humrep/dew356.
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• [19] 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.
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• [23] Succination is Increased on Select Proteins in the Brainstem of the NADH dehydrogenase (ubiquinone) Fe-S protein 4 (Ndufs4) Knockout Mouse, a Model of Leigh Syndrome.Mol Cell Proteomics. 2016 Feb;15(2):445-61. doi: 10.1074/mcp.M115.051516. Epub 2015 Oct 8.
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• [32] Expression and functional analysis of SURF1 in Leigh syndrome patients with cytochrome c oxidase deficiency.Hum Mol Genet. 1999 Dec;8(13):2541-9. doi: 10.1093/hmg/8.13.2541.
• [33] Complete Plasmodium falciparum liver-stage development in liver-chimeric mice.J Clin Invest. 2012 Oct;122(10):3618-28. doi: 10.1172/JCI62684. Epub 2012 Sep 10.
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• [35] Bioenergetic Impairment in Congenital Muscular Dystrophy Type 1A and Leigh Syndrome Muscle Cells.Sci Rep. 2017 Apr 3;7:45272. doi: 10.1038/srep45272.
• [36] Mutations in GTPBP3 cause a mitochondrial translation defect associated with hypertrophic cardiomyopathy, lactic acidosis, and encephalopathy. Am J Hum Genet. 2014 Dec 4;95(6):708-20. doi: 10.1016/j.ajhg.2014.10.017. Epub 2014 Nov 26.
• [37] Mutated ND2 impairs mitochondrial complex I assembly and leads to Leigh syndrome.Mol Genet Metab. 2007 Jan;90(1):10-4. doi: 10.1016/j.ymgme.2006.08.003. Epub 2006 Sep 22.
• [38] Novel mutation of ND4 gene identified by targeted next-generation sequencing in patient with Leigh syndrome.J Hum Genet. 2017 Feb;62(2):291-297. doi: 10.1038/jhg.2016.127. Epub 2016 Oct 20.
• [39] Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP. Nat Commun. 2019 May 30;10(1):2373. doi: 10.1038/s41467-019-10016-3.
• [40] Mitochondrial DNA mutations in Leigh syndrome and their phylogenetic implications.J Hum Genet. 2000;45(2):69-75. doi: 10.1007/s100380050014.
• [41] Mutations in mitochondrial complex I assembly factor NDUFAF3 cause Leigh syndrome. Mol Genet Metab. 2017 Mar;120(3):243-246. doi: 10.1016/j.ymgme.2016.12.005. Epub 2016 Dec 11.
• [42] NDUFS6 related Leigh syndrome: a case report and review of the literature.J Hum Genet. 2019 Jul;64(7):637-645. doi: 10.1038/s10038-019-0594-4. Epub 2019 Apr 4.
• [43] PARL deficiency in mouse causes Complex III defects, coenzyme Q depletion, and Leigh-like syndrome.Proc Natl Acad Sci U S A. 2019 Jan 2;116(1):277-286. doi: 10.1073/pnas.1811938116. Epub 2018 Dec 21.
• [44] Cytochrome c oxidase biogenesis in a patient with a mutation in COX10 gene. Ann Neurol. 2004 Oct;56(4):560-4. doi: 10.1002/ana.20229.