LS
MCID: LGH001
MIFTS: 65

Leigh Disease (LS) malady

Genetic diseases, Rare diseases, Neuronal diseases, Metabolic diseases categories
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Summaries for Leigh Disease

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NIH Rare Diseases:42 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 based summary: Leigh Disease, also known as leigh syndrome, is related to mitochondrial complex i deficiency and melas syndrome, and has symptoms including 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:21 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.

CDC:3 CDC's Strategic National Stockpile (SNS) has large quantities of medicine and medical supplies to protect the American public if there is a public health emergency (terrorist attack, flu outbreak, earthquake) severe enough to cause local supplies to run out. Once Federal and local authorities agree that the SNS is needed, medicines will be delivered to any state in the U.S. in time for them to be effective. Each state has plans to receive and distribute SNS medicine and medical supplies to local communities as quickly as possible.

NINDS:43 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:46 256000

Aliases & Classifications for Leigh Disease

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Sources:
8Disease Ontology, 42NIH Rare Diseases, 20GeneTests, 22GTR, 21Genetics Home Reference, 43NINDS, 46OMIM, 10DISEASES, 44Novoseek, 48Orphanet, 62UMLS, 34MeSH, 39NCIt, 57SNOMED-CT, 26ICD10 via Orphanet, 63UMLS via Orphanet
See all sources

Leigh Disease, Aliases & Descriptions:

Name: Leigh Disease 8 21 10 62
Leigh Syndrome 8 42 20 22 21 46 44 62
Leigh's Disease 8 42 21 43
Infantile Necrotizing Encephalomyelopathy 8 62
Subacute Necrotizing Encephalomyelopathy 21 62
Mils 48 62
Maternally-Inherited Infantile Subacute Necrotizing Encephalopathy 48
Necrotizing Encephalopathy, Infantile Subacute, of Leigh 62
Necrotizing Encephalopathy Infantile Subacute of Leigh 42
Encephalopathy, Subacute Necrotizing, Infantile 62
Encephalopathy, Subacute Necrotizing, Juvenile 62
 
Infantile Subacute Necrotizing Encephalopathy 21
Juvenile Subacute Necrotizing Encephalopathy 21
Encephalopathy, Subacute Necrotizing 62
Subacute Necrotizing Encephalopathy 42
Maternally-Inherited Leigh Syndrome 48
Maternally Inherited Leigh Syndrome 62
Leigh's Necrotizing Encephalopathy 42
Maternally-Inherited Leigh Disease 48
Sne 42
Ls 42


Classifications:



Characteristics (Orphanet epidemiological data):

48
mils:
Inheritance: Mitochondrial inheritance; Age of onset: Neonatal/infancy


External Ids:

Disease Ontology8 DOID:3652
OMIM46 256000
MeSH34 D007888
SNOMED-CT57 29570005
NCIt39 C84814
ICD10 via Orphanet26 G31.8
UMLS via Orphanet63 C2931092

Related Diseases for Leigh Disease

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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 89)
idRelated DiseaseScoreTop Affiliating Genes
1mitochondrial complex i deficiency31.0MT-ND3, NDUFS7, MT-ND6, MT-ND5
2melas syndrome30.6MT-ND5, MT-TL1
3mitochondrial disorders30.4MT-CO1, MT-ATP6, MT-CO3
4cytochrome-c oxidase deficiency disease30.3MT-CO1, MT-CO2
5leber hereditary optic neuropathy29.9MT-ND5, MT-ATP6, MT-ND6, MT-CO3, MT-ND1, MT-ND4
6mitochondrial dna-associated leigh syndrome and narp29.6MT-ND6, MT-TK, MT-ND5, MT-ATP6, MT-ND3, MT-ND2
7leigh syndrome, french canadian type10.5
8lactic acidosis10.5MT-ND5
9lymphosarcoma10.5
10x-linked leigh syndrome10.4
11merrf syndrome10.4MT-ND5, MT-TK
12leber hereditary optic neuropathy with dystonia10.4MT-ND6, MT-ND4
13central pontine myelinolysis10.3
14beriberi10.3
15pyruvate decarboxylase deficiency10.3
16spasmus nutans10.3
17sparganosis10.3MT-CO1, MT-ND3
18pyruvate carboxylase deficiency disease10.3
19leigh syndrome due to mitochondrial complex i deficiency10.3
20early myoclonic encephalopathy10.3MT-ND5, NDUFS4
21leukodystrophy10.3
22brain disease10.2NDUFS4, MT-ND5, BCS1L
23alzheimer disease mitochondrial10.2MT-ND2, MT-ND1
24leigh-like syndrome10.2
25lichen sclerosus10.2
26dystonia10.2
27leigh syndrome, due to cox deficiency10.2
28leigh syndrome due to cytochrome c oxidase deficiency10.2
29leigh syndrome due to mitochondrial cox4 deficiency10.2
30optic nerve disease10.2MT-ND6, MT-ND4
31neuropathy10.1
32maternally inherited leigh syndrome10.1
33parkinson's disease10.1NDUFS4, MT-ND1, MT-ND5
34laron syndrome10.1
35cowpox10.1
36hirschsprung's disease10.1
37neuroblastoma10.1
38bell's palsy10.1
39benign recurrent intrahepatic cholestasis 210.1
40west syndrome10.0
41cataract10.0
42pearson syndrome10.0
43wolff-parkinson-white syndrome10.0
44biotinidase deficiency10.0
45moyamoya disease10.0
46fukuyama congenital muscular dystrophy10.0
47biotin-responsive basal ganglia 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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Symptoms by clinical synopsis from OMIM:

256000

Clinical features from OMIM:

256000

HPO human phenotypes related to Leigh Disease:

(show all 42)
id Description Frequency HPO Source Accession
1 strabismus hallmark (90%) HP:0000486
2 nystagmus hallmark (90%) HP:0000639
3 muscular hypotonia hallmark (90%) HP:0001252
4 respiratory insufficiency hallmark (90%) HP:0002093
5 incoordination hallmark (90%) HP:0002311
6 abnormality of movement hallmark (90%) HP:0100022
7 cognitive impairment hallmark (90%) HP:0100543
8 ophthalmoparesis typical (50%) HP:0000597
9 optic atrophy typical (50%) HP:0000648
10 seizures typical (50%) HP:0001250
11 autosomal recessive inheritance HP:0000007
12 sensorineural hearing impairment HP:0000407
13 pigmentary retinopathy HP:0000580
14 ophthalmoplegia HP:0000602
15 nystagmus HP:0000639
16 optic atrophy HP:0000648
17 emotional lability HP:0000712
18 hypertrichosis HP:0000998
19 intellectual disability HP:0001249
20 seizures HP:0001250
21 ataxia HP:0001251
22 muscular hypotonia HP:0001252
23 spasticity HP:0001257
24 dysarthria HP:0001260
25 global developmental delay HP:0001263
26 dystonia HP:0001332
27 hyperreflexia HP:0001347
28 hepatocellular necrosis HP:0001404
29 heterogeneous HP:0001425
30 mitochondrial inheritance HP:0001427
31 failure to thrive HP:0001508
32 increased serum lactate HP:0002151
33 gliosis HP:0002171
34 gliosis HP:0002171
35 increased csf lactate HP:0002490
36 abnormal pattern of respiration HP:0002793
37 respiratory failure HP:0002878
38 lactic acidosis HP:0003128
39 infantile onset HP:0003593
40 progressive disorder HP:0003676
41 phenotypic variability HP:0003812
42 cns demyelination HP:0007305

Drugs & Therapeutics for Leigh Disease

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Drug clinical trials:

Search ClinicalTrials for Leigh Disease

Search NIH Clinical Center for Leigh Disease

Genetic Tests for Leigh Disease

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Genetic tests related to Leigh Disease:

id Genetic test Affiliating Genes
1 Leigh Syndrome (nuclear Dna Mutation)20 22 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)20
3 Leigh Syndrome (mtdna Deletion)20
4 Leigh's Disease22

Anatomical Context for Leigh Disease

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MalaCards organs/tissues related to Leigh Disease:

32
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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Articles related to Leigh Disease:

(show top 50)    (show all 70)
idTitleAuthorsYear
1
ECHS1 mutations in Leigh disease: a new inborn error of metabolism affecting valine metabolism. (25125611)
2014
2
A new mutation in MT-ND1 m.3928G>C p.V208L causes Leigh disease with infantile spasms. (24063851)
2013
3
The "Double Panda" Sign in Leigh Disease. (23599247)
2013
4
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
5
Adult Leigh disease without failure to thrive. (21712670)
2011
6
Subthalamic nuclei involvement in Leigh disease with cytochrome c oxidase deficiency. (21748946)
2011
7
Leigh disease presenting in utero due to a novel missense mutation in the mitochondrial DNA-ND3. (20202874)
2010
8
Leigh disease with brainstem involvement in complex I deficiency due to assembly factor NDUFAF2 defect. (20571988)
2010
9
Low citrulline in Leigh disease: still a biomarker of maternally inherited Leigh syndrome. (20472868)
2010
10
NDUFA2 complex I mutation leads to Leigh disease. (18513682)
2008
11
Answer to case of the month #110. Magnetic resonance imaging and spectroscopy in Leigh disease. (16881477)
2006
12
Bull's-eye maculopathy in an infant with Leigh disease. (16815282)
2006
13
Outpatient anesthesia for oral surgery in a juvenile with Leigh disease. (16048155)
2005
14
Cochlear degeneration in leigh disease: histopathologic features. (15564853)
2004
15
Self-inflicted orodental injury in a child with Leigh disease. (14706032)
2004
16
Leigh disease associated with a novel mitochondrial DNA ND5 mutation. (11938446)
2002
17
Neuropathologic and clinical features in eight Chinese patients with Leigh disease. (12174968)
2002
18
A novel mutation in the SURF1 gene in a child with Leigh disease, peripheral neuropathy, and cytochrome-c oxidase deficiency. (12026244)
2002
19
Cytochrome c oxidase partial deficiency-associated Leigh disease presenting as an extrapyramidal syndrome. (11510939)
2001
20
Leigh disease: clinical, neuroradiologic, and biochemical study of three new cases with cytochrome c oxidase deficiency. (11510937)
2001
21
Abnormal calcium homeostasis in fibroblasts from patients with Leigh disease. (11341780)
2001
22
Leigh disease caused by the mitochondrial DNA G14459A mutation in unrelated families. (10894222)
2000
23
Outcome of thiamine treatment in a child with Leigh disease due to thiamine-responsive pyruvate dehydrogenase deficiency. (10872106)
2000
24
Vocal cord paralysis and hypoventilation in a patient with suspected Leigh disease. (10207933)
1999
25
3-Methylglutaconic aciduria and hypermethioninaemia in a child with clinical and neuroradiological findings of Leigh disease. (10399091)
1999
26
Mutations of SURF-1 in Leigh disease associated with cytochrome c oxidase deficiency. (9837813)
1998
27
Electrophysiological brainstem dysfunction in a child with Leigh disease. (9258969)
1997
28
Quiz case of the month. Subacute necrotizing mitochondrial encephalopathy (Leigh disease). (9440999)
1997
29
Association of the mitochondrial 8344 MERRF mutation with maternally inherited spinocerebellar degeneration and Leigh disease. (8559379)
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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UniProtKB/Swiss-Prot genetic disease variations for Leigh Disease:

64 (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:

6
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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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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Compounds for genes affiliated with Leigh Disease

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Sources:
44Novoseek, 11DrugBank, 28IUPHAR, 24HMDB
See all sources

Compounds related to Leigh Disease according to GeneCards/GeneDecks:

(show all 29)
idCompoundScoreTop Affiliating Genes
1thenoyltrifluoroacetone44 1111.5NDUFS4, SDHA
2ubiquinone4410.5MT-ND4, SDHA, NDUFS4
3solium4410.4MT-ATP6, MT-CO1, MT-ND1
4oligomycin4410.4MT-ATP6, NDUFS4
5rotenone4410.4MT-ND6, MT-ND1, NDUFS4
6succinate4410.4NDUFS4, SDHA, MT-ND4, MT-CO1
7nad+4410.3MT-ND4, SDHA, NDUFS4
8cholic acid44 28 24 1113.3MT-CO3, MT-CO2, MT-CO1
9citrate4410.3NDUFS4, MT-CO1, MT-CO3, MT-CO2
10pyruvate4410.2MT-ND1, MT-ND3, NDUFS4, MT-ND4
11valine4410.2MT-ND2, MT-ND5, MT-ND6, MT-ND4, MT-ND1
12glyceraldehyde 3-phosphate4410.2MT-CO2, SDHA, NDUFS4
13methionine4410.1MT-ND1, MT-ND6, MT-ND2, MT-ND5
14threonine4410.1MT-ND5, MT-ND3, MT-ND2, NDUFS4, MT-ND1, MT-ND4
15hydrogen44 2411.0NDUFS4, MT-CO2, MT-ATP6, MT-CO1
16QH22410.0NDUFA10, NDUFS4, NDUFS7, MT-ND2, MT-ND6, MT-ND1
17Sulfide2410.0NDUFA10, NDUFS4, NDUFS7, MT-ND2, MT-ND6, MT-ND1
18oxygen44 2411.0SDHA, MT-CO1, MT-ND6, MT-CO2, MT-ND2, MT-ATP6
19Ubiquinone Q22410.0MT-ND1, MT-ND6, MT-ND2, NDUFS7, NDUFS4, NDUFA10
20FAD2410.0SDHA, NDUFS4, NDUFA10, NDUFS7, MT-ND2, MT-ND6
21Ubiquinol 8249.9NDUFS7, MT-ND5, MT-ND3, MT-ND2, MT-ND6, MT-ND1
22alanine449.9MT-ND5, MT-ND1, MT-ND3, MT-ND2, MT-ND6
23lactate449.9MT-ND1, MT-CO2, NDUFS4, MT-ND4
24atp44 2810.9MT-CO1, MT-ND1, MT-CO3, MT-ND5, MT-CO2, MT-ATP6
25nad28 2410.8NDUFA10, MT-ND4, MT-ND1, MT-ND6, MT-ND2, MT-ND3
26Ubiquinone Q1249.8MT-ND5, MT-ND3, MT-ND2, MT-ND6, MT-ND1, MT-ND4
27iron44 2410.8MT-ND2, SDHA, MT-ND4, NDUFA10, NDUFS4, NDUFS7
28glucose449.6MT-CO1, NDUFS4, MT-CO3, MT-ND1, MT-ND4
29nadh44 24 1111.2NDUFA10, SDHA, MT-ND4, NDUFAF2, NDUFS4, MT-ND2

GO Terms for genes affiliated with Leigh Disease

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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:00612010.2NDUFA10, NDUFS4, NDUFS7
2mitochondrial respiratory chain complex I assemblyGO:03298110.2NDUFS4, NDUFS7, BCS1L
3respiratory electron transport chainGO:02290410.0NDUFA10, NDUFS4, NDUFS7, SDHA
4cellular metabolic processGO:0442379.8SDHA, NDUFS7, NDUFS4, NDUFA10

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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3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
34MeSH
35MESH via Orphanet
36MGI
39NCIt
40NDF-RT
43NINDS
44Novoseek
46OMIM
47OMIM via Orphanet
51PubMed
52QIAGEN
58SNOMED-CT via Orphanet
62UMLS
63UMLS via Orphanet