LS
MCID: LGH001
MIFTS: 64

Leigh Disease (LS) malady

Genetic diseases, Rare diseases, Neuronal diseases categories

Summaries for Leigh Disease

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22Genetics Home Reference, 44NIH Rare Diseases, 45NINDS, 48OMIM, 34MalaCards
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NIH Rare Diseases:44 Leigh syndrome is a rare inherited degenerative neurological condition that affects the central nervous system. it usually begins in infants between the ages of three months and two years. rarely, it occurs in teenagers and adults. signs and symptoms usually progress rapidly. the earliest signs may be poor sucking ability, and the loss of head control and motor skills. these symptoms may be accompanied by loss of appetite, vomiting, irritability, continuous crying, and seizures. as the disorder progresses, symptoms may also include generalized weakness, lack of muscle tone, and episodes of lactic acidosis, which can lead to impairment of respiratory and kidney function. there are several different gene mutations that can cause this condition. leigh syndrome can be caused by mutations in mitochondrial dna or nuclear dna. last updated: 10/5/2011

MalaCards: Leigh Disease, also known as leigh syndrome, is related to mitochondrial complex i deficiency and mitochondrial dna-associated leigh syndrome and narp. An important gene associated with Leigh Disease is NDUFS7 (NADH dehydrogenase (ubiquinone) Fe-S protein 7, 20kDa (NADH-coenzyme Q reductase)), and among its related pathways are Cardiac muscle contraction and tRNA Aminoacylation. The compounds thenoyltrifluoroacetone and ubiquinone have been mentioned in the context of this disorder. Affiliated tissues include cerebellum, spinal cord and kidney.

Genetics Home Reference:22 Leigh syndrome is a severe neurological disorder that typically arises in the first year of life. This condition is characterized by progressive loss of mental and movement abilities (psychomotor regression) and typically results in death within a couple of years, usually due to respiratory failure. A small number of individuals develop symptoms in adulthood or have symptoms that worsen more slowly.

NINDS:45 Leigh's disease is a rare inherited neurometabolic disorder that affects the central nervous system. This progressive disorder begins in infants between the ages of three months and two years.

Description from OMIM:48 256000

Aliases & Classifications for Leigh Disease

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9Disease Ontology, 22Genetics Home Reference, 11DISEASES, 63UMLS, 44NIH Rare Diseases, 45NINDS, 21GeneTests, 23GTR, 48OMIM, 46Novoseek, 50Orphanet, 59SNOMED-CT, 41NCIt, 36MeSH, 27ICD10 via Orphanet, 64UMLS via Orphanet
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Classifications:

Malacards categories (disease lists): (See all malacards categories)
Global: Genetic diseases, Rare diseases
Anatomical: Neuronal diseases


Characteristics (Orphanet epidemiological data):

50
mils:
Inheritance: Mitochondrial inheritance; Age of onset: Neonatal/infancy


Aliases & Descriptions:

leigh disease 9 22 11 63
leigh syndrome 9 44 21 23 22 48 46
leigh's disease 9 44 22 45
mils 50 63
maternally-inherited infantile subacute necrotizing encephalopathy 50
necrotizing encephalopathy infantile subacute of leigh 44
encephalopathy, subacute necrotizing, infantile 63
encephalopathy, subacute necrotizing, juvenile 63
infantile subacute necrotizing encephalopathy 22
juvenile subacute necrotizing encephalopathy 22
infantile necrotizing encephalomyelopathy 9
subacute necrotizing encephalomyelopathy 22
subacute necrotizing encephalopathy 44
maternally-inherited leigh syndrome 50
maternally inherited leigh syndrome 63
leigh's necrotizing encephalopathy 44
maternally-inherited leigh disease 50
sne 44
ls 44


External Ids:

Disease Ontology9 DOID:3652
NCIt41 C84814
OMIM48 256000
SNOMED-CT59 29570005
MeSH36 D007888
ICD10 via Orphanet27 G31.8
UMLS via Orphanet64 C2931092

Related Diseases for Leigh Disease

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18GeneCards, 19GeneDecks
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Diseases in the Leigh Disease family:

Leigh-Like Syndrome

Diseases related to Leigh Disease via text searches within MalaCards or GeneCards/GeneDecks gene sharing:

(show top 50)    (show all 88)
idRelated DiseaseScoreTop Affiliating Genes
1mitochondrial complex i deficiency30.7MT-ND3, NDUFS7, MT-ND6, MT-ND5
2mitochondrial dna-associated leigh syndrome and narp30.3MT-ND6, MT-TK, MT-ND5, MT-ATP6, MT-ND3, MT-ND2
3melas syndrome30.2MT-ND5, MT-TL1
4mitochondrial disorders30.1MT-CO1, MT-ATP6, MT-CO3
5cytochrome-c oxidase deficiency disease30.1MT-CO1, MT-CO2
6leber hereditary optic neuropathy30.0MT-ND5, MT-ATP6, MT-ND6, MT-CO3, MT-ND1, MT-ND4
7lymphosarcoma10.4
8x-linked leigh syndrome10.4
9central pontine myelinolysis10.3
10beriberi10.3
11pyruvate decarboxylase deficiency10.3
12spasmus nutans10.3
13pyruvate carboxylase deficiency disease10.3
14leukodystrophy10.3
15leigh syndrome due to mitochondrial complex i deficiency10.3
16leigh-like syndrome10.2
17dystonia10.2
18optic atrophy10.2
19leigh syndrome, due to cox deficiency10.2
20leigh syndrome due to cytochrome c oxidase deficiency10.2
21leigh syndrome due to mitochondrial cox4 deficiency10.2
22leigh syndrome, french canadian type10.1
23maternally inherited leigh syndrome10.1
24lactic acidosis10.1MT-ND5
25cowpox10.1
26laron syndrome10.1
27hirschsprung's disease10.1
28neuroblastoma10.1
29lichen sclerosus10.1
30leber hereditary optic neuropathy with dystonia10.1MT-ND6, MT-ND4
31merrf syndrome10.1MT-ND5, MT-TK
32sparganosis10.1MT-CO1, MT-ND3
33bell's palsy10.1
34early myoclonic encephalopathy10.1MT-ND5, NDUFS4
35alzheimer disease mitochondrial10.1MT-ND2, MT-ND1
36brain disease10.1NDUFS4, MT-ND5, BCS1L
37benign recurrent intrahepatic cholestasis 210.0
38back pain10.0
39optic nerve disease10.0MT-ND6, MT-ND4
40parkinson's disease10.0NDUFS4, MT-ND1, MT-ND5
41wolff-parkinson-white syndrome10.0
42pearson syndrome10.0
43biotinidase deficiency10.0
44fukuyama congenital muscular dystrophy10.0
45west syndrome10.0
46biotin-responsive basal ganglia disease10.0
47moyamoya disease10.0
48basal ganglia disease10.0
49congenital muscular dystrophy10.0
50hypertrichosis10.0

Graphical network of the top 20 diseases related to Leigh Disease:



Diseases related to leigh disease

Symptoms for Leigh Disease

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48OMIM
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Symptoms by clinical synopsis from OMIM:

256000

Clinical features from OMIM:

256000

Drugs & Therapeutics for Leigh Disease

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Sources:
6CenterWatch, 43NIH Clinical Center, 7ClinicalTrials, 63UMLS, 42NDF-RT
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Approved drugs:

Search CenterWatch for Leigh Disease

Drug clinical trials:

Search ClinicalTrials for Leigh Disease

Search NIH Clinical Center for Leigh Disease

Search CenterWatch for Leigh Disease

Genetic Tests for Leigh Disease

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21GeneTests, 23GTR
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Genetic tests related to Leigh Disease:

id Genetic test Affiliating Genes
1 Leigh Syndrome (nuclear Dna Mutation)21 23 BCS1L, COX10, DLD, MTFMT, NDUFA1, NDUFA10, NDUFAF2, NDUFAF6, NDUFS1, NDUFS3 (show all 18)

NDUFS4, NDUFS7, NDUFS8, NDUFV1, SCO1, SCO2, SDHA, SURF1

2 Leigh Syndrome (mtdna Mutation)21
3 Leigh Syndrome (mtdna Deletion)21
4 Leigh's Disease23

Anatomical Context for Leigh Disease

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Sources:
34MalaCards
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MalaCards organs/tissues related to Leigh Disease:

34
Cerebellum, Spinal cord, Kidney, Thalamus, Eye, Brain

Animal Models for Leigh Disease or affiliated genes

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Publications for Leigh Disease

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Sources:
53PubMed
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Articles related to Leigh Disease:

(show top 50)    (show all 67)
idTitleAuthorsYear
1
A new mutation in MT-ND1 m.3928G>C p.V208L causes Leigh disease with infantile spasms. (24063851)
2013
2
The "Double Panda" Sign in Leigh Disease. (23599247)
2013
3
Clinical and molecular features of an infant patient affected by Leigh Disease associated to m.14459G>A mitochondrial DNA mutation: a case report. (21749722)
2011
4
Adult Leigh disease without failure to thrive. (21712670)
2011
5
Subthalamic nuclei involvement in Leigh disease with cytochrome c oxidase deficiency. (21748946)
2011
6
Leigh disease presenting in utero due to a novel missense mutation in the mitochondrial DNA-ND3. (20202874)
2010
7
Leigh disease with brainstem involvement in complex I deficiency due to assembly factor NDUFAF2 defect. (20571988)
2010
8
Low citrulline in Leigh disease: still a biomarker of maternally inherited Leigh syndrome. (20472868)
2010
9
NDUFA2 complex I mutation leads to Leigh disease. (18513682)
2008
10
Answer to case of the month #110. Magnetic resonance imaging and spectroscopy in Leigh disease. (16881477)
2006
11
Bull's-eye maculopathy in an infant with Leigh disease. (16815282)
2006
12
Outpatient anesthesia for oral surgery in a juvenile with Leigh disease. (16048155)
2005
13
Cochlear degeneration in leigh disease: histopathologic features. (15564853)
2004
14
Self-inflicted orodental injury in a child with Leigh disease. (14706032)
2004
15
Leigh disease associated with a novel mitochondrial DNA ND5 mutation. (11938446)
2002
16
Neuropathologic and clinical features in eight Chinese patients with Leigh disease. (12174968)
2002
17
A novel mutation in the SURF1 gene in a child with Leigh disease, peripheral neuropathy, and cytochrome-c oxidase deficiency. (12026244)
2002
18
Cytochrome c oxidase partial deficiency-associated Leigh disease presenting as an extrapyramidal syndrome. (11510939)
2001
19
Leigh disease: clinical, neuroradiologic, and biochemical study of three new cases with cytochrome c oxidase deficiency. (11510937)
2001
20
Abnormal calcium homeostasis in fibroblasts from patients with Leigh disease. (11341780)
2001
21
Leigh disease caused by the mitochondrial DNA G14459A mutation in unrelated families. (10894222)
2000
22
Outcome of thiamine treatment in a child with Leigh disease due to thiamine-responsive pyruvate dehydrogenase deficiency. (10872106)
2000
23
Vocal cord paralysis and hypoventilation in a patient with suspected Leigh disease. (10207933)
1999
24
3-Methylglutaconic aciduria and hypermethioninaemia in a child with clinical and neuroradiological findings of Leigh disease. (10399091)
1999
25
Mutations of SURF-1 in Leigh disease associated with cytochrome c oxidase deficiency. (9837813)
1998
26
Electrophysiological brainstem dysfunction in a child with Leigh disease. (9258969)
1997
27
Quiz case of the month. Subacute necrotizing mitochondrial encephalopathy (Leigh disease). (9440999)
1997
28
Association of the mitochondrial 8344 MERRF mutation with maternally inherited spinocerebellar degeneration and Leigh disease. (8559379)
1996
29
Leigh disease with deficiency of lipoamide dehydrogenase: treatment failure with dichloroacetate. (8652022)
1996
30
Connatal Leigh disease. (7554683)
1995
31
Leigh disease (subacute necrotizing encephalomyelopathy): report of one case. (8213161)
1993
32
Leigh disease (subacute necrotizing encephalomyelopathy): MR documentation of the evolution of an acute attack. (8237695)
1993
33
Assessment and therapy monitoring of Leigh disease by MRI and proton spectroscopy. (1558578)
1992
34
Heteroplasmic mtDNA mutation (T----G) at 8993 can cause Leigh disease when the percentage of abnormal mtDNA is high. (1550128)
1992
35
Subacute necrotizing encephalomyelopathy (Leigh disease): CT and MRI appearances. (2287541)
1990
36
Ultrasonography and magnetic resonance imaging in Leigh disease. (2242175)
1990
37
Leigh disease: value of CT in presymptomatic patients and variability of the lesions with time. (2925905)
1989
38
Pelizaeus-Merzbacher disease with thiamine deficiency or Leigh disease with extensive involvement of white matter? Case report. (2548793)
1989
39
Leigh disease (subacute necrotizing encephalomyelopathy): CT and MR in five cases. (3335670)
1988
40
Subacute necrotizing encephalomyelopathy (Leigh disease): CT study. (3786750)
1987
41
Abnormal kinetic behavior of cytochrome oxidase in a case of Leigh disease. (2821802)
1987
42
Pyruvate dehydrogenase complex deficiency as a cause of subacute necrotizing encephalopathy (Leigh disease). (3103091)
1987
43
Clinical presentation of mitochondrial respiratory chain defects in NADH-coenzyme Q reductase and cytochrome oxidase: clues to pathogenesis of Leigh disease. (3027293)
1987
44
Subacute necrotizing encephalomyelopathy (Leigh disease): report of a case with Lennox-Gastaut syndrome. (4083386)
1985
45
Pyruvate dehydrogenase activity is not deficient in the brain of three autopsied cases with Leigh disease (subacute necrotizing encephalomyelopathy, SNE). (6437963)
1984
46
Putaminal lesions in Leigh disease. (7114815)
1982
47
Computerized tomography in subacute necrotizing encephalomyelopathy (Leigh disease). (7294735)
1981
48
Defective activation of the pyruvate dehydrogenase complex in subacute necrotizing encephalomyelopathy (Leigh disease). (119480)
1979
49
Thiamine triphosphate levels and histopathology. Correlation in Leigh disease. (985153)
1976
50
Subacute necrotizing encephalomyelopathy. Rapidly fatal course of Leigh disease in a 5-year-old child. (4825591)
1974

Variations for Leigh Disease

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Sources:
65UniProtKB/Swiss-Prot, 1 National Center for Biotechnology Information (Clinvar), 8dbSNP
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UniProtKB/Swiss-Prot genetic disease variations for Leigh Disease:

65 (show all 25)
id Symbol AA change Variation ID SNP ID
1COX15p.Arg217TrpVAR_019596rs28939711
2COX15p.Ser344ProVAR_033117
3MT-ATP6p.Leu156ArgVAR_000793
4MT-ATP6p.Leu156ProVAR_000794
5MT-ATP6p.Leu217ProVAR_000797
6MT-ND3p.Ala47ThrVAR_035092
7MT-ND5p.Phe124LeuVAR_035424
8NDUFAF5p.Leu159PheVAR_067956
9NDUFS8p.Pro79LeuVAR_019538rs28939679
10NDUFS8p.Arg102HisVAR_019539
11NDUFV1p.Thr423MetVAR_008847
12POLGp.Gly848SerVAR_023675
13POLGp.Arg232HisVAR_058871
14SDHAp.Arg554TrpVAR_002449
15SDHAp.Ala524ValVAR_016878
16SURF1p.Gly124GluVAR_007450rs28933402
17SURF1p.Ile246ThrVAR_007452
18SURF1p.Gly124ArgVAR_015258
19SURF1p.Tyr274AspVAR_015259
20SURF1p.Leu90ProVAR_068649
21SURF1p.Val177GlyVAR_068650
22SURF1p.Gly205GluVAR_068651
23SURF1p.Met235ThrVAR_068652
24SURF1p.Ala248AspVAR_068653
25SURF1p.Gly257ArgVAR_068654

Clinvar genetic disease variations for Leigh Disease:

1
id Gene Name Type Significance SNP ID Assembly Location
1SDHANM_004168.3(SDHA): c.1664G> A (p.Gly555Glu)single nucleotide variantPathogenicrs137852768GRCh37Chr 5, 251453: 251453
2MT-TVm.1624C> Tsingle nucleotide variantPathogenicrs199476144GRCh37Chr MT, 1624: 1624
3MT-TWm.5537_5538insTinsertionPathogenicrs199474672GRCh37Chr MT, 5537: 5538
4MT-TKm.8344A> Gsingle nucleotide variantPathogenicrs118192098GRCh37Chr MT, 8344: 8344
5MT-ATP6m.8993T> Gsingle nucleotide variantPathogenicrs199476133GRCh37Chr MT, 8993: 8993
6MT-ATP6m.8993T> Csingle nucleotide variantPathogenicrs199476133GRCh37Chr MT, 8993: 8993
7MT-ATP6m.9176T> Csingle nucleotide variantPathogenicrs199476135GRCh37Chr MT, 9176: 9176
8MT-ATP6m.9185T> Csingle nucleotide variantPathogenicrs199476138GRCh37Chr MT, 9185: 9185
9MT-ATP6m.9176T> Gsingle nucleotide variantPathogenicrs199476135GRCh37Chr MT, 9176: 9176

Expression for genes affiliated with Leigh Disease

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2BioGPS, 16Gene Expression Omnibus DataSets
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Expression patterns in normal tissues for genes affiliated with Leigh Disease

Search GEO for disease gene expression data for Leigh Disease.

Pathways for genes affiliated with Leigh Disease

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51PathCards, 31KEGG, 56Reactome, 39NCBI BioSystems Database
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Compounds for genes affiliated with Leigh Disease

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46Novoseek, 12DrugBank, 30IUPHAR, 25HMDB
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Compounds related to Leigh Disease according to GeneCards/GeneDecks:

(show all 29)
idCompoundScoreTop Affiliating Genes
1thenoyltrifluoroacetone46 1211.5NDUFS4, SDHA
2ubiquinone4610.5MT-ND4, SDHA, NDUFS4
3solium4610.4MT-ATP6, MT-CO1, MT-ND1
4oligomycin4610.4MT-ATP6, NDUFS4
5rotenone4610.4MT-ND6, MT-ND1, NDUFS4
6succinate4610.4NDUFS4, SDHA, MT-ND4, MT-CO1
7cholic acid46 30 25 1213.3MT-CO3, MT-CO2, MT-CO1
8nad+4610.3MT-ND4, SDHA, NDUFS4
9citrate4610.3NDUFS4, MT-CO1, MT-CO3, MT-CO2
10pyruvate4610.3MT-ND1, MT-ND3, NDUFS4, MT-ND4
11valine4610.2MT-ND2, MT-ND5, MT-ND6, MT-ND4, MT-ND1
12methionine4610.2MT-ND1, MT-ND6, MT-ND2, MT-ND5
13glyceraldehyde 3-phosphate4610.2MT-CO2, SDHA, NDUFS4
14threonine4610.1MT-ND5, MT-ND3, MT-ND2, NDUFS4, MT-ND1, MT-ND4
15QH22510.0NDUFA10, NDUFS4, NDUFS7, MT-ND2, MT-ND6, MT-ND1
16Sulfide2510.0NDUFA10, NDUFS4, NDUFS7, MT-ND2, MT-ND6, MT-ND1
17hydrogen46 2511.0NDUFS4, MT-CO2, MT-ATP6, MT-CO1
18Ubiquinone Q22510.0MT-ND1, MT-ND6, MT-ND2, NDUFS7, NDUFS4, NDUFA10
19oxygen46 2511.0SDHA, MT-CO1, MT-ND6, MT-CO2, MT-ND2, MT-ATP6
20FAD2510.0SDHA, NDUFS4, NDUFA10, NDUFS7, MT-ND2, MT-ND6
21Ubiquinol 82510.0NDUFS7, MT-ND5, MT-ND3, MT-ND2, MT-ND6, MT-ND1
22alanine4610.0MT-ND5, MT-ND1, MT-ND3, MT-ND2, MT-ND6
23lactate469.9MT-ND1, MT-CO2, NDUFS4, MT-ND4
24nad30 2510.9NDUFA10, MT-ND4, MT-ND1, MT-ND6, MT-ND2, MT-ND3
25atp46 3010.9MT-CO1, MT-ND1, MT-CO3, MT-ND5, MT-CO2, MT-ATP6
26Ubiquinone Q1259.8MT-ND5, MT-ND3, MT-ND2, MT-ND6, MT-ND1, MT-ND4
27iron46 2510.8MT-ND2, SDHA, MT-ND4, NDUFA10, NDUFS4, NDUFS7
28glucose469.6MT-CO1, NDUFS4, MT-CO3, MT-ND1, MT-ND4
29nadh46 25 1211.3NDUFA10, SDHA, MT-ND4, NDUFAF2, NDUFS4, MT-ND2

GO Terms for genes affiliated with Leigh Disease

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17Gene Ontology
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Cellular components related to Leigh Disease according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1mitochondrial inner membraneGO:00574310.1NDUFA10, NDUFS4, NDUFS7, SDHA
2mitochondrial respiratory chain complex IGO:0057479.9NDUFA10, NDUFS4, NDUFS7

Biological processes related to Leigh Disease according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1mitochondrial electron transport, NADH to ubiquinoneGO:00612010.2NDUFS7, NDUFS4, NDUFA10
2mitochondrial respiratory chain complex I assemblyGO:03298110.2NDUFS4, NDUFS7, BCS1L
3respiratory electron transport chainGO:02290410.0NDUFA10, NDUFS4, SDHA, NDUFS7
4cellular metabolic processGO:0442379.8NDUFS4, NDUFA10, NDUFS7, SDHA

Molecular functions related to Leigh Disease according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1NADH dehydrogenase (ubiquinone) activityGO:00813710.2NDUFA10, NDUFS4, NDUFS7

Products for genes affiliated with Leigh Disease

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Sources for Leigh Disease

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4CDC
14ExPASy
15FMA
23GTR
24HGMD
25HMDB
26ICD10
27ICD10 via Orphanet
28ICD9CM
30IUPHAR
31KEGG
36MeSH
37MESH via Orphanet
38MGI
41NCIt
42NDF-RT
45NINDS
46Novoseek
48OMIM
49OMIM via Orphanet
53PubMed
54QIAGEN
60SNOMED-CT via Orphanet
63UMLS
64UMLS via Orphanet