LDYT
MCID: LBR031
MIFTS: 40

Leber Optic Atrophy and Dystonia (LDYT)

Categories: Eye diseases, Genetic diseases, Neuronal diseases, Rare diseases
Data Licensing
For inquiries, contact:

Aliases & Classifications for Leber Optic Atrophy and Dystonia

MalaCards integrated aliases for Leber Optic Atrophy and Dystonia:

Name: Leber Optic Atrophy and Dystonia 57 11 19 73 28 5 71
Marsden Syndrome 57 11 19 73
Ldyt 57 11 19 73
Leber Hereditary Optic Neuropathy with Dystonia 57 19 73
Familial Dystonia with Visual Failure and Striatal Lucencies 11 73
Leber Hereditary Optic Neuropathy and Dystonia 11 14
Dystonia, Familial, with Visual Failure and Striatal Lucencies 57
Dystonia Familial, with Visual Failure and Striatal Lucencies 19
Leber's Hereditary Optic Neuropathy with Dystonia 19
Leber Optic Atrophy with Dystonia 11
Lhon and Dystonia 19

Characteristics:


Inheritance:

Mitochondrial 57

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
onset of dystonia is in childhood
onset of optic neuropathy is usually in early adulthood
patients may show both optic neuropathy and dystonia or only 1 disorder
considered part of a spectrum of leber hereditary optic atrophy (lhon, )


Classifications:



Summaries for Leber Optic Atrophy and Dystonia

GARD: 19 Leber hereditary optic neuropathy (LHON) with dystonia is a very rare variant of LHON where an individual has LHON associated with dystonia. Dystonia involves involuntary muscle contractions, tremors, and other uncontrolled movements. It is caused by genetic changes in one of three mitochondrial genes: MT-ND1, MT-ND3, MT-ND4, and MT-ND6. Other features that have been associated with this condition include difficulty walking, muscle wasting, scoliosis, dysphagia, dysarthria, intellectual disability, dementia, and spasticity. The dystonia usually begins in childhood; vision loss may begin in early adulthood.

MalaCards based summary: Leber Optic Atrophy and Dystonia, also known as marsden syndrome, is related to hereditary optic neuropathy and neuropathy, and has symptoms including dystonia, athetosis and bradykinesia. An important gene associated with Leber Optic Atrophy and Dystonia is MT-ND6 (Mitochondrially Encoded NADH:Ubiquinone Oxidoreductase Core Subunit 6), and among its related pathways/superpathways are Metabolism and Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.. Affiliated tissues include skeletal muscle and eye, and related phenotypes are intellectual disability and spasticity

UniProtKB/Swiss-Prot: 73 A form of Leber hereditary optic neuropathy, a mitochondrial disease resulting in bilateral painless loss of central vision due to selective degeneration of the retinal ganglion cells and their axons. The disorder shows incomplete penetrance and male predominance. LDYT is characterized by the association of optic atrophy and central vision loss with dystonia.

Disease Ontology: 11 A Leber plus disease characterized by Leber hereditary optic neuropathy and dystonia that has material basis in mutation in the mitochondrial genes MTND6, MTND4, MTND1 or MTND3 that make up the mitochondrial complex I.

More information from OMIM: 500001

Related Diseases for Leber Optic Atrophy and Dystonia

Diseases related to Leber Optic Atrophy and Dystonia via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 78)
# Related Disease Score Top Affiliating Genes
1 hereditary optic neuropathy 30.9 MT-ND6 MT-ND5 MT-ND4 MT-ND3
2 neuropathy 30.7 MT-ND6 MT-ND5 MT-ND4 MT-ND3 MT-ND1
3 optic nerve disease 30.3 MT-ND6 MT-ND5 MT-ND4 MT-ND3 MT-ND1 LINGO1
4 dystonia 12 30.3 THAP1 SGCE GCH1
5 lactic acidosis 30.2 MT-ND6 MT-ND5 MT-ND4 MT-ND3 MT-ND1
6 mitochondrial disease 30.2 MT-ND6 MT-ND5 MT-ND4 MT-ND3 MT-ND1
7 mitochondrial encephalomyopathy 30.2 MT-ND6 MT-ND5 MT-ND4 MT-ND3 MT-ND1
8 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes 30.0 MT-ND6 MT-ND5 MT-ND4 MT-ND3 MT-ND1 ADI1
9 leber hereditary optic neuropathy, modifier of 30.0 MT-ND6 MT-ND5 MT-ND4 MT-ND3 MT-ND1 CHM
10 dystonia 29.8 THAP1 SGCE PLA2G6 MT-ND6 MT-ND4 MT-ND3
11 leigh syndrome 29.7 NDUFC1 MT-ND6 MT-ND5 MT-ND4 MT-ND3 MT-ND1
12 leber plus disease 28.1 THAP1 SGCE PLA2G6 MT-ND6 MT-ND5 MT-ND4
13 toxascariasis 10.3 MT-ND4 MT-ND1
14 3-methylglutaconic aciduria, type iii 10.3
15 mitochondrial complex i deficiency, mitochondrial type 1 10.3
16 hereditary dystonia 10.3
17 fasciolopsiasis 10.2 MT-ND6 MT-ND1
18 congenital nystagmus 1 10.2 MT-ND6 MT-ND1
19 nutritional optic neuropathy 10.2 MT-ND6 MT-ND4
20 toxic optic neuropathy 10.2 MT-ND6 MT-ND4
21 severe congenital neutropenia 1 10.2 MT-ND5 MT-ND1
22 progressive myoclonus epilepsy 9 10.2 MT-ND5 MT-ND3
23 optic atrophy 7 with or without auditory neuropathy 10.2 MT-ND6 MT-ND4
24 deafness, nonsyndromic sensorineural, mitochondrial 10.2 MT-ND4 MT-ND1
25 mitochondrial myopathy, infantile, transient 10.2 MT-ND5 MT-ND1
26 parkinson disease 6, autosomal recessive early-onset 10.2 MT-ND6 MT-ND5
27 myiasis 10.2 MT-ND5 MT-ND1
28 parathyroid oncocytic adenoma 10.2 MT-ND6 MT-ND3 MT-ND1
29 scotoma 10.1 MT-ND6 MT-ND4 MT-ND1
30 neuropathy, ataxia, and retinitis pigmentosa 10.1 MT-ND6 MT-ND4
31 taeniasis 10.1 MT-ND5 MT-ND1
32 coenurosis 10.1 MT-ND5 MT-ND4 MT-ND1
33 diphyllobothriasis 10.1 MT-ND5 MT-ND3 MT-ND1
34 dicrocoeliasis 10.1 MT-ND5 MT-ND3 MT-ND1
35 deafness, aminoglycoside-induced 10.1 MT-ND6 MT-ND4
36 cystic echinococcosis 10.1 MT-ND5 MT-ND1
37 hyperphenylalaninemia, bh4-deficient, b 10.1 SGCE GCH1
38 hereditary lymphedema ii 10.1 THAP1 SGCE
39 mitochondrial dna depletion syndrome 4a 10.1 MT-ND5 MT-ND4 MT-ND1
40 conversion disorder 10.1 THAP1 SGCE
41 mitochondrial complex i deficiency, nuclear type 16 10.1 MT-ND6 MT-ND4 MT-ND3 MT-ND1
42 pearson marrow-pancreas syndrome 10.0 MT-ND6 MT-ND4 MT-ND3 MT-ND1
43 chronic progressive external ophthalmoplegia 10.0 MT-ND6 MT-ND4 MT-ND3 MT-ND1
44 lymphatic malformation 5 10.0 THAP1 SGCE
45 cysticercosis 10.0 MT-ND5 MT-ND1
46 ancylostomiasis 10.0 MT-ND5 MT-ND4 MT-ND3 MT-ND1
47 sparganosis 10.0 MT-ND5 MT-ND4 MT-ND3 MT-ND1
48 cortical blindness 10.0 MT-ND6 MT-ND5 MT-ND4 MT-ND1
49 mitochondrial dna depletion syndrome 10.0 MT-ND6 MT-ND5 MT-ND4 MT-ND1
50 focal dystonia 10.0 THAP1 SGCE GCH1

Graphical network of the top 20 diseases related to Leber Optic Atrophy and Dystonia:



Diseases related to Leber Optic Atrophy and Dystonia

Symptoms & Phenotypes for Leber Optic Atrophy and Dystonia

Human phenotypes related to Leber Optic Atrophy and Dystonia:

30 (show all 17)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 30 HP:0001249
2 spasticity 30 HP:0001257
3 scoliosis 30 HP:0002650
4 abnormality of eye movement 30 HP:0000496
5 dysarthria 30 HP:0001260
6 dysphagia 30 HP:0002015
7 optic atrophy 30 HP:0000648
8 skeletal muscle atrophy 30 HP:0003202
9 increased serum lactate 30 HP:0002151
10 dystonia 30 HP:0001332
11 peripheral neuropathy 30 HP:0009830
12 increased csf lactate 30 HP:0002490
13 athetosis 30 HP:0002305
14 dementia 30 HP:0000726
15 visual loss 30 HP:0000572
16 bradykinesia 30 HP:0002067
17 leber optic atrophy 30 HP:0001112

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Neurologic Central Nervous System:
spasticity
dysarthria
dysphagia
dystonia
athetosis
more
Head And Neck Eyes:
optic atrophy
loss of vision
abnormal extraocular movements

Laboratory Abnormalities:
increased serum and csf lactate
decreased mitochondrial complex i activity

Skeletal Spine:
scoliosis

Muscle Soft Tissue:
amyotrophy

Clinical features from OMIM®:

500001 (Updated 08-Dec-2022)

UMLS symptoms related to Leber Optic Atrophy and Dystonia:


dystonia; athetosis; bradykinesia; muscle spasticity; unspecified visual loss

Drugs & Therapeutics for Leber Optic Atrophy and Dystonia

Search Clinical Trials, NIH Clinical Center for Leber Optic Atrophy and Dystonia

Genetic Tests for Leber Optic Atrophy and Dystonia

Genetic tests related to Leber Optic Atrophy and Dystonia:

# Genetic test Affiliating Genes
1 Leber Optic Atrophy and Dystonia 28

Anatomical Context for Leber Optic Atrophy and Dystonia

Organs/tissues related to Leber Optic Atrophy and Dystonia:

MalaCards : Skeletal Muscle, Eye

Publications for Leber Optic Atrophy and Dystonia

Articles related to Leber Optic Atrophy and Dystonia:

(show all 20)
# Title Authors PMID Year
1
Mitochondrial ND3 as the novel causative gene for Leber hereditary optic neuropathy and dystonia. 62 57 5
19458970 2009
2
A MELAS-associated ND1 mutation causing leber hereditary optic neuropathy and spastic dystonia. 62 57 5
17562939 2007
3
Leber's hereditary optic neuropathy with dystonia in a Japanese family. 62 57 5
16380132 2006
4
A mitochondrial DNA mutation at nucleotide pair 14459 of the NADH dehydrogenase subunit 6 gene associated with maternally inherited Leber hereditary optic neuropathy and dystonia. 62 57 5
8016139 1994
5
Genetic and biochemical impairment of mitochondrial complex I activity in a family with Leber hereditary optic neuropathy and hereditary spastic dystonia. 57 5
8644732 1996
6
A novel ND3 mitochondrial DNA mutation in three Korean children with basal ganglia lesions and complex I deficiency. 5
17413873 2007
7
A novel recurrent mitochondrial DNA mutation in ND3 gene is associated with isolated complex I deficiency causing Leigh syndrome and dystonia. 5
17152068 2007
8
Mutations of the mitochondrial ND1 gene as a cause of MELAS. 5
15466014 2004
9
Variable clinical manifestation of homoplasmic G14459A mitochondrial DNA mutation. 5
14735585 2004
10
Late-onset encephalopathy associated with a C11777A mutation of mitochondrial DNA. 5
12707444 2003
11
Leigh disease caused by the mitochondrial DNA G14459A mutation in unrelated families. 5
10894222 2000
12
Leber's hereditary optic neuropathy plus dystonia is caused by a mitochondrial DNA point mutation. 5
7654063 1995
13
Hereditary spastic dystonia with Leber's hereditary optic neuropathy: neuropathological findings. 5
1469456 1992
14
Leber's disease and dystonia: a mitochondrial disease. 57
3736869 1986
15
Familial dystonia and visual failure with striatal CT lucencies. 57
3711913 1986
16
Dementia of the Alzheimer's type and Huntington's disease. 57
3155827 1985
17
Familial holotopistic striatal necrosis. 57
5805975 1969
18
Leber hereditary optic neuropathy and dystonia overlapping mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes due to m.14459G>A mutation. 62
33779865 2021
19
The mitochondrial DNA 10197 G > A mutation causes MELAS/Leigh overlap syndrome presenting with acute auditory agnosia. 62
24708134 2015
20
Use of transmitochondrial cybrids to assign a complex I defect to the mitochondrial DNA-encoded NADH dehydrogenase subunit 6 gene mutation at nucleotide pair 14459 that causes Leber hereditary optic neuropathy and dystonia. 62
8622678 1996

Variations for Leber Optic Atrophy and Dystonia

ClinVar genetic disease variations for Leber Optic Atrophy and Dystonia:

5
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 MT-ND6 m.14596A>T SNV Pathogenic
9690 rs387906424 GRCh37: MT:14596-14596
GRCh38: MT:14596-14596
2 MT-ND4 m.11696G>A SNV Pathogenic
9710 rs200873900 GRCh37: MT:11696-11696
GRCh38: MT:11696-11696
3 MT-ND6 m.14459G>A SNV Pathogenic
9689 rs199476105 GRCh37: MT:14459-14459
GRCh38: MT:14459-14459
4 MT-ND3 m.10197G>A SNV Pathogenic
9715 rs267606891 GRCh37: MT:10197-10197
GRCh38: MT:10197-10197
5 MT-ND1 m.3697G>A SNV Pathogenic
9733 rs199476122 GRCh37: MT:3697-3697
GRCh38: MT:3697-3697

UniProtKB/Swiss-Prot genetic disease variations for Leber Optic Atrophy and Dystonia:

73
# Symbol AA change Variation ID SNP ID
1 MT-ND4 p.Val313Ile VAR_008393 rs200873900
2 MT-ND6 p.Ala72Val VAR_004764 rs199476105
3 MT-ND6 p.Ile26Met VAR_008394 rs387906424

Expression for Leber Optic Atrophy and Dystonia

Search GEO for disease gene expression data for Leber Optic Atrophy and Dystonia.

Pathways for Leber Optic Atrophy and Dystonia

GO Terms for Leber Optic Atrophy and Dystonia

Cellular components related to Leber Optic Atrophy and Dystonia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 membrane GO:0016020 10.37 SGCE PLA2G6 NDUFC1 NDUFB1 MT-ND6 MT-ND5
2 membrane GO:0016021 10.37 SGCE PLA2G6 NDUFC1 NDUFB1 MT-ND6 MT-ND5
3 mitochondrion GO:0005739 10.06 PLA2G6 NDUFC1 NDUFB1 MT-ND6 MT-ND5 MT-ND4
4 mitochondrial inner membrane GO:0005743 10 NDUFC1 NDUFB1 MT-ND6 MT-ND5 MT-ND4 MT-ND3
5 mitochondrial respiratory chain complex I GO:0005747 9.8 NDUFC1 NDUFB1 MT-ND6 MT-ND5 MT-ND4 MT-ND3
6 mitochondrial membrane GO:0031966 9.65 MT-ND1 MT-ND3 MT-ND4 MT-ND6
7 respirasome GO:0070469 9.17 NDUFC1 NDUFB1 MT-ND6 MT-ND5 MT-ND4 MT-ND3

Biological processes related to Leber Optic Atrophy and Dystonia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial respiratory chain complex I assembly GO:0032981 10.03 NDUFC1 NDUFB1 MT-ND6 MT-ND5 MT-ND4 MT-ND1
2 aerobic respiration GO:0009060 10 MT-ND1 MT-ND3 MT-ND4 MT-ND5 MT-ND6 NDUFB1
3 proton motive force-driven mitochondrial ATP synthesis GO:0042776 9.8 NDUFC1 NDUFB1 MT-ND6 MT-ND5 MT-ND4 MT-ND3
4 electron transport coupled proton transport GO:0015990 9.62 MT-ND5 MT-ND4
5 mitochondrial electron transport, NADH to ubiquinone GO:0006120 9.47 NDUFC1 NDUFB1 MT-ND6 MT-ND5 MT-ND4 MT-ND3
6 ATP synthesis coupled electron transport GO:0042773 9.37 MT-ND5 MT-ND4

Molecular functions related to Leber Optic Atrophy and Dystonia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 NADH dehydrogenase (ubiquinone) activity GO:0008137 9.47 NDUFC1 NDUFB1 MT-ND6 MT-ND5 MT-ND4 MT-ND3
2 NADH dehydrogenase activity GO:0003954 9.43 MT-ND5 MT-ND4 MT-ND1

Sources for Leber Optic Atrophy and Dystonia

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
Content
Loading form....