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MCID: LBR031
MIFTS: 43

Leber Optic Atrophy and Dystonia

Categories: Rare diseases, Genetic diseases, Eye diseases, Neuronal diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes Drugs
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Aliases & Classifications for Leber Optic Atrophy and Dystonia

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MalaCards integrated aliases for Leber Optic Atrophy and Dystonia:

Name: Leber Optic Atrophy and Dystonia 57 53 75 73
Leber Hereditary Optic Neuropathy with Dystonia 57 53 75 29 6
Marsden Syndrome 57 53 75
Ldyt 57 53 75
Dystonia, Familial, with Visual Failure and Striatal Lucencies 57
Dystonia Familial, with Visual Failure and Striatal Lucencies 53
Familial Dystonia with Visual Failure and Striatal Lucencies 75
Leber Hereditary Optic Neuropathy with Dystonia; Ldyt 57
Leber's Hereditary Optic Neuropathy with Dystonia 53
Leber Hereditary Optic Neuropathy and Dystonia 37
Lhon and Dystonia 53

Characteristics:

OMIM:

57
Inheritance:
mitochondrial

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, )


HPO:

32
leber optic atrophy and dystonia:
Inheritance mitochondrial inheritance


Classifications:

MalaCards categories:
Global: Rare diseases Genetic diseases
Anatomical: Eye diseases Neuronal diseases
See all MalaCards categories (disease lists)


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Summaries for Leber Optic Atrophy and Dystonia

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NIH Rare Diseases : 53 Leber hereditary optic neuropathy (LHON) with dystonia is a very rare variant of LHON where an individual has LHON associated with dystonia, which involves involuntary muscle contractions, tremors, and other unctrolled movements. It is caused by mutations 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 leber hereditary optic neuropathy with dystonia, is related to optic nerve disease and neuropathy, and has symptoms including athetosis, dystonia and muscle spasticity. 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 Oxidative phosphorylation and Metabolism. The drugs Idebenone and Antioxidants have been mentioned in the context of this disorder. Affiliated tissues include eye and skeletal muscle, and related phenotypes are abnormality of eye movement and intellectual disability

UniProtKB/Swiss-Prot : 75 Leber hereditary optic neuropathy with dystonia: Part of a spectrum of Leber hereditary optic neuropathy. It is characterized by the association of optic atrophy and central vision loss with dystonia.

Description from OMIM: 500001
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Related Diseases for Leber Optic Atrophy and Dystonia

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

(show all 29)
# Related Disease Score Top Affiliating Genes
1 optic nerve disease 29.5 MT-ND1 MT-ND4 MT-ND6
2 neuropathy 29.3 MT-ND1 MT-ND4 MT-ND6
3 dystonia 28.7 MT-ND3 MT-ND4 MT-ND6
4 leber hereditary optic neuropathy 28.1 MT-ND1 MT-ND3 MT-ND4 MT-ND6
5 deafness, nonsyndromic sensorineural, mitochondrial 9.7 MT-ND1 MT-ND4
6 cortical blindness 9.7 MT-ND4 MT-ND6
7 sparganosis 9.6 MT-ND3 MT-ND4
8 striatonigral degeneration, infantile, mitochondrial 9.5 MT-ND3 MT-ND4
9 myopathy, lactic acidosis, and sideroblastic anemia 3 9.5 MT-ND3 MT-ND4
10 striatonigral degeneration, infantile 9.5 MT-ND3 MT-ND4
11 peripheral nervous system disease 9.5 MT-ND4 MT-ND6
12 ataxia and polyneuropathy, adult-onset 9.4 MT-ND3 MT-ND4
13 myopathy, lactic acidosis, and sideroblastic anemia 9.4 MT-ND3 MT-ND4
14 encephalomyopathy 9.4 MT-ND1 MT-ND4 MT-ND6
15 cranial nerve disease 9.4 MT-ND1 MT-ND4 MT-ND6
16 mitochondrial metabolism disease 9.3 MT-ND3 MT-ND6
17 kearns-sayre syndrome 9.3 MT-ND1 MT-ND4 MT-ND6
18 mitochondrial myopathy 9.3 MT-ND1 MT-ND4 MT-ND6
19 lactic acidosis 9.3 MT-ND1 MT-ND4 MT-ND6
20 3-methylglutaconic aciduria, type iii 9.2 MT-ND4 MT-ND6
21 familial colorectal cancer 9.0 MT-ND3 MT-ND4 MT-ND6
22 mitochondrial dna-associated leigh syndrome and narp 8.4 MT-ND1 MT-ND3 MT-ND4 MT-ND6
23 leber optic atrophy 8.4 MT-ND1 MT-ND3 MT-ND4 MT-ND6
24 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes 8.4 MT-ND1 MT-ND3 MT-ND4 MT-ND6
25 mitochondrial encephalomyopathy 8.4 MT-ND1 MT-ND3 MT-ND4 MT-ND6
26 mitochondrial disorders 8.4 MT-ND1 MT-ND3 MT-ND4 MT-ND6
27 mitochondrial complex i deficiency 8.4 MT-ND1 MT-ND3 MT-ND4 MT-ND6
28 leigh syndrome 8.4 MT-ND1 MT-ND3 MT-ND4 MT-ND6
29 myopathy 8.3 MT-ND1 MT-ND3 MT-ND4 MT-ND6

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



Diseases related to Leber Optic Atrophy and Dystonia
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Symptoms & Phenotypes for Leber Optic Atrophy and Dystonia

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Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
spasticity
dysarthria
dysphagia
dystonia
dementia
more
Head And Neck Eyes:
optic atrophy
abnormal extraocular movements
loss of vision

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

Skeletal Spine:
scoliosis

Muscle Soft Tissue:
amyotrophy


Clinical features from OMIM:

500001

Human phenotypes related to Leber Optic Atrophy and Dystonia:

32 (show all 17)
# Description HPO Frequency HPO Source Accession
1 abnormality of eye movement 32 HP:0000496
2 intellectual disability 32 HP:0001249
3 spasticity 32 HP:0001257
4 dysarthria 32 HP:0001260
5 dysphagia 32 HP:0002015
6 scoliosis 32 HP:0002650
7 optic atrophy 32 HP:0000648
8 skeletal muscle atrophy 32 HP:0003202
9 peripheral neuropathy 32 HP:0009830
10 dystonia 32 HP:0001332
11 increased serum lactate 32 HP:0002151
12 visual loss 32 HP:0000572
13 dementia 32 HP:0000726
14 bradykinesia 32 HP:0002067
15 athetosis 32 HP:0002305
16 increased csf lactate 32 HP:0002490
17 leber optic atrophy 32 HP:0001112

UMLS symptoms related to Leber Optic Atrophy and Dystonia:


athetosis, dystonia, muscle spasticity, bradykinesia, unspecified visual loss
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Drugs & Therapeutics for Leber Optic Atrophy and Dystonia

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Drugs for Leber Optic Atrophy and Dystonia (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 37)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Idebenone Approved, Investigational Phase 4,Phase 3,Phase 2 58186-27-9
2 Antioxidants Phase 4,Phase 3,Phase 2
3 Protective Agents Phase 4,Phase 3,Phase 2
4
Curcumin Approved, Investigational Phase 3 458-37-7 969516
5 Antirheumatic Agents Phase 3,Phase 2
6 Ubiquinone Phase 3,Phase 2
7 Analgesics Phase 3
8 Micronutrients Phase 3,Phase 2
9 Analgesics, Non-Narcotic Phase 3
10 Trace Elements Phase 3,Phase 2
11 Peripheral Nervous System Agents Phase 3
12 Anti-Inflammatory Agents Phase 3
13 Anti-Inflammatory Agents, Non-Steroidal Phase 3
14 Central Nervous System Depressants Phase 3
15 Anesthetics Phase 3
16 Pharmaceutical Solutions Phase 3,Phase 2
17 Anti-Infective Agents, Local Phase 3
18
Miconazole Approved, Investigational, Vet_approved Phase 2 22916-47-8 4189
19
Cysteamine Approved, Investigational Phase 2 60-23-1 6058
20 Cyclosporins Phase 2
21 Dermatologic Agents Phase 2
22 Immunosuppressive Agents Phase 2
23 Anti-Infective Agents Phase 2
24 Antifungal Agents Phase 2
25 Calcineurin Inhibitors Phase 2
26 Ophthalmic Solutions Phase 2
27 Neuroprotective Agents Phase 1
28
Triamcinolone Approved, Vet_approved Not Applicable 124-94-7 31307
29
Tocopherol Approved, Investigational, Nutraceutical 1406-66-2 14986
30
Vitamin E Approved, Nutraceutical, Vet_approved 59-02-9 14985
31 triamcinolone acetonide Not Applicable
32 Triamcinolone diacetate Not Applicable
33 Triamcinolone hexacetonide Not Applicable
34 Tocopherols
35 Tocotrienol, alpha
36 Tocotrienols
37 Tocotrienol Investigational, Nutraceutical 6829-55-6

Interventional clinical trials:

(show all 31)
# Name Status NCT ID Phase Drugs
1 Study to Assess the Efficacy and Safety of Raxone in LHON Patients Recruiting NCT02774005 Phase 4 Idebenone
2 A Randomized, Double-blind, Placebo-controlled Trial of Curcumin in Leber's Hereditary Optic Neuropathy (LHON) Completed NCT00528151 Phase 3 curcumin
3 Efficacy and Safety Study of Bilateral Intravitreal Injection of GS010 for the Treatment of Vision Loss up to 1 Year From Onset in LHON Due to the ND4 Mutation Recruiting NCT03293524 Phase 3 Placebo
4 Safety and Efficacy Study of Gene Therapy for The Treatment of Leber's Hereditary Optic Neuropathy Active, not recruiting NCT03153293 Phase 2, Phase 3 rAAV2-ND4
5 Efficacy Study of GS010 for Treatment of Vision Loss From 7 Months to 1 Year From Onset in LHON Due to the ND4 Mutation Active, not recruiting NCT02652780 Phase 3
6 Efficacy Study of GS010 for the Treatment of Vision Loss up to 6 Months From Onset in LHON Due to the ND4 Mutation Active, not recruiting NCT02652767 Phase 3
7 Study With Idebenone in Patients With Chronic Vision Loss Due to Leber's Hereditary Optic Neuropathy (LHON) Withdrawn NCT01495715 Phase 3 Idebenone;Placebo
8 Trial of Cyclosporine in the Acute Phase of Leber Hereditary Optic Neuropathy Unknown status NCT02176733 Phase 2 cyclosporine
9 Study to Assess Efficacy,Safety and Tolerability of Idebenone in the Treatment of Leber's Hereditary Optic Neuropathy Completed NCT00747487 Phase 2 Idebenone;Placebo
10 The KHENERGY Study Completed NCT02909400 Phase 2 KH176;placebo
11 Open-Label, Dose-Escalating Study Assessing Safety, Tolerability, Efficacy, of RP103 in Mitochondrial Disease Completed NCT02023866 Phase 2 Cysteamine Bitartrate
12 Safety Evaluation of Gene Therapy in Leber Hereditary Optic Neuropathy (LHON) Patients Active, not recruiting NCT02064569 Phase 1, Phase 2
13 A Study Investigating the Safety, Tolerability, and Efficacy of Elamipretide (MTP-131) Topical Ophthalmic Solution for the Treatment of Leber's Hereditary Optic Neuropathy Active, not recruiting NCT02693119 Phase 2 elamipretide (MTP-131) 1% topical ophthalmic solution;Vehicle topical ophthalmic solution
14 Near-infrared Light-emitting Diode (NIR-LED) Therapy for Leber's Hereditary Optic Neuropathy (LHON) Terminated NCT01389817 Phase 1, Phase 2
15 A Long-term Extension of Study RP103-MITO-001 (NCT02023866) to Assess Cysteamine Bitartrate Delayed-release Capsules (RP103) in Children With Inherited Mitochondrial Disease Terminated NCT02473445 Phase 2 Cysteamine Bitartrate
16 A Dose-escalating Clinical Trial With KH176 Completed NCT02544217 Phase 1 KH176;placebo
17 Safety Study of a Single IVT Injection of QPI-1007 in Chronic Optic Nerve Atrophy and Recent Onset NAION Patients Completed NCT01064505 Phase 1 QPI-1007 at various doses
18 Safety Study of an Adeno-associated Virus Vector for Gene Therapy of Leber's Hereditary Optic Neuropathy Recruiting NCT02161380 Phase 1 injection of scAAV2-P1ND4v2 5.00x10e9 vg (Low),;injection of scAAV2-P1ND4v2 2.46X10e10 vg (Med);injection of scAAV2-P1ND4v2 1.0X10e11vg (High)
19 Safety and Efficacy Study of rAAV2-ND4 Treatment of Leber Hereditary Optic Neuropathy (LHON) Completed NCT01267422 Not Applicable rAAV2-ND4
20 Leber Hereditary Optic Neuropathy (LHON) Historical Case Record Survey Completed NCT01892943
21 RHODOS Follow-up Single-visit Study Completed NCT01421381
22 Historical Case Record Survey of Visual Acuity Data From Patients With Leber's Hereditary Optic Neuropathy (LHON) Recruiting NCT02796274
23 REALITY LHON Registry Recruiting NCT03295071
24 Post Authorisation Safety Study With Raxone in LHON Patients Recruiting NCT02771379 Idebenone
25 RESCUE and REVERSE Long-term Follow-up Recruiting NCT03406104
26 Efficacy Study of Gene Therapy for The Treatment of Acute LHON Onset Within Three Months Recruiting NCT03428178 Not Applicable rAAV2-ND4
27 Biomechanics of Optic Neuropathy Recruiting NCT02982499
28 Stem Cell Ophthalmology Treatment Study II Recruiting NCT03011541 Not Applicable
29 New Non-invasive Modalities for Assessing Retinal Structure and Function Recruiting NCT03475173 Not Applicable
30 North American Mitochondrial Disease Consortium Patient Registry and Biorepository (NAMDC) Recruiting NCT01694940
31 Emergency Administration of EPI-743 to a Single Patient With Leber's Hereditary Optic Neuropathy [LHON] No longer available NCT02300753 EPI-743

Search NIH Clinical Center for Leber Optic Atrophy and Dystonia

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Genetic Tests for Leber Optic Atrophy and Dystonia

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Genetic tests related to Leber Optic Atrophy and Dystonia:

# Genetic test Affiliating Genes
1 Leber Hereditary Optic Neuropathy with Dystonia 29
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Anatomical Context for Leber Optic Atrophy and Dystonia

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MalaCards organs/tissues related to Leber Optic Atrophy and Dystonia:

41
Eye, Skeletal Muscle
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Publications for Leber Optic Atrophy and Dystonia

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Articles related to Leber Optic Atrophy and Dystonia:

# Title Authors Year
1
Leber's hereditary optic neuropathy with dystonia in a Japanese family. ( 16380132 )
2006
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Variations for Leber Optic Atrophy and Dystonia

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

75
# 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

ClinVar genetic disease variations for Leber Optic Atrophy and Dystonia:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 MT-ND6 m.14459G> A single nucleotide variant Pathogenic rs199476105 GRCh37 Chromosome MT, 14459: 14459
2 MT-ND6 m.14459G> A single nucleotide variant Pathogenic rs199476105 GRCh38 Chromosome MT, 14459: 14459
3 MT-ND6 m.14596A> T single nucleotide variant Pathogenic rs387906424 GRCh37 Chromosome MT, 14596: 14596
4 MT-ND6 m.14596A> T single nucleotide variant Pathogenic rs387906424 GRCh38 Chromosome MT, 14596: 14596
5 MT-ND4 m.11696G> A single nucleotide variant Pathogenic rs200873900 GRCh37 Chromosome MT, 11696: 11696
6 MT-ND4 m.11696G> A single nucleotide variant Pathogenic rs200873900 GRCh38 Chromosome MT, 11696: 11696
7 MT-ND3 m.10197G> A single nucleotide variant Pathogenic rs267606891 GRCh37 Chromosome MT, 10197: 10197
8 MT-ND3 m.10197G> A single nucleotide variant Pathogenic rs267606891 GRCh38 Chromosome MT, 10197: 10197
9 MT-ND1 m.3697G> A single nucleotide variant Pathogenic rs199476122 GRCh37 Chromosome MT, 3697: 3697
10 MT-ND1 m.3697G> A single nucleotide variant Pathogenic rs199476122 GRCh38 Chromosome MT, 3697: 3697
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Expression for Leber Optic Atrophy and Dystonia

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

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Pathways related to Leber Optic Atrophy and Dystonia according to KEGG:

37
# Name Kegg Source Accession
1 Oxidative phosphorylation hsa00190

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

# Super pathways Score Top Affiliating Genes
1
Metabolism 66
Show member pathways
 13.09 MT-ND1 MT-ND3 MT-ND4 MT-ND6
2
Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. 66
Show member pathways
 12.51 MT-ND1 MT-ND3 MT-ND4 MT-ND6
3
GABAergic synapse 37
Show member pathways
 11.44 MT-ND1 MT-ND3 MT-ND4 MT-ND6
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GO Terms for Leber Optic Atrophy and Dystonia

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

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.62 MT-ND1 MT-ND3 MT-ND4 MT-ND6
2 mitochondrial inner membrane GO:0005743 9.56 MT-ND1 MT-ND3 MT-ND4 MT-ND6
3 mitochondrial respiratory chain complex I GO:0005747 9.33 MT-ND1 MT-ND3 MT-ND4
4 mitochondrial membrane GO:0031966 9.26 MT-ND1 MT-ND3 MT-ND4 MT-ND6
5 respiratory chain GO:0070469 8.92 MT-ND1 MT-ND3 MT-ND4 MT-ND6

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

# Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.46 MT-ND1 MT-ND3 MT-ND4 MT-ND6
2 response to nicotine GO:0035094 9.26 MT-ND4 MT-ND6
3 mitochondrial respiratory chain complex I assembly GO:0032981 9.26 MT-ND1 MT-ND3 MT-ND4 MT-ND6
4 mitochondrial electron transport, NADH to ubiquinone GO:0006120 8.92 MT-ND1 MT-ND3 MT-ND4 MT-ND6

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

# Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity GO:0016491 9.26 MT-ND1 MT-ND3 MT-ND4 MT-ND6
2 NADH dehydrogenase activity GO:0003954 9.16 MT-ND1 MT-ND4
3 NADH dehydrogenase (ubiquinone) activity GO:0008137 8.92 MT-ND1 MT-ND3 MT-ND4 MT-ND6
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Sources for Leber Optic Atrophy and Dystonia

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3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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