MILS
MCID: MTC112
MIFTS: 36

Mitochondrial Dna-Associated Leigh Syndrome (MILS)

Categories: Rare diseases

Aliases & Classifications for Mitochondrial Dna-Associated Leigh Syndrome

MalaCards integrated aliases for Mitochondrial Dna-Associated Leigh Syndrome:

Name: Mitochondrial Dna-Associated Leigh Syndrome 53
Maternally Inherited Leigh Syndrome 53 72
Subacute Necrotizing Encephalomyelopathy Maternally Inherited 53
Leigh Disease, Maternally Inherited 53
Mils 53

Classifications:



External Ids:

UMLS 72 C2931092

Summaries for Mitochondrial Dna-Associated Leigh Syndrome

NIH Rare Diseases : 53 Mitochondrial DNA-associated Leigh syndrome is a progressive brain disorder that usually appears in infancy or early childhood. Affected children may experience vomiting, seizures, delayed development, muscle weakness, and problems with movement. Heart disease, kidney problems, and difficulty breathing can also occur in people with this disorder. Mitochondrial DNA-associated Leigh syndrome is a subtype of Leigh syndrome and is caused by changes in mitochondrial DNA. Mutations in at least 11 mitochondrial genes have been found to cause mtDNA-associated Leigh syndrome. This condition has an inheritance pattern known as maternal or mitochondrial inheritance. Because mitochondria can be passed from one generation to the next only through egg cells (not through sperm cells), only females pass mitochondrial DNA-associated Leigh syndrome to their children.

MalaCards based summary : Mitochondrial Dna-Associated Leigh Syndrome, also known as maternally inherited leigh syndrome, is related to aceruloplasminemia and ataxia and polyneuropathy, adult-onset. An important gene associated with Mitochondrial Dna-Associated Leigh Syndrome is MT-ATP6 (Mitochondrially Encoded ATP Synthase Membrane 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.. The drugs Sargramostim and Melphalan have been mentioned in the context of this disorder. Affiliated tissues include brain, heart and kidney, and related phenotypes are increased csf lactate and abnormality of krebs cycle metabolism

Related Diseases for Mitochondrial Dna-Associated Leigh Syndrome

Diseases related to Mitochondrial Dna-Associated Leigh Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 67)
# Related Disease Score Top Affiliating Genes
1 aceruloplasminemia 29.6 SURF1 MT-ATP6 BCS1L
2 ataxia and polyneuropathy, adult-onset 29.3 MT-ND4L MT-ND3 MT-CO3 MT-ATP8 MT-ATP6
3 retinitis pigmentosa 28.6 MT-ND4L MT-ND3 MT-CO3 MT-CO2 MT-ATP8 MT-ATP6
4 leigh syndrome 28.2 SURF1 SDHA MT-ND4L MT-ND3 MT-CO3 MT-CO2
5 mitochondrial metabolism disease 27.2 SURF1 MT-ND3 MT-CO2 MT-ATP6 COX15 COX10
6 mitochondrial dna-associated leigh syndrome and narp 12.9
7 cholestasis, benign recurrent intrahepatic, 2 11.3
8 brain injury 10.4
9 traumatic brain injury 10.4
10 periodic paralysis with later-onset distal motor neuropathy 10.4 MT-ATP8 MT-ATP6
11 isolated atp synthase deficiency 10.3 MT-ATP8 MT-ATP6
12 liver disease 10.2
13 posttransplant acute limbic encephalitis 10.2
14 lactic acidosis 10.2
15 mitochondrial disorders 10.2
16 encephalopathy 10.2
17 diphyllobothriasis 10.1 MT-ND3 MT-ATP8
18 neuropathy, ataxia, and retinitis pigmentosa 10.1
19 chorea, childhood-onset, with psychomotor retardation 10.1
20 neuroretinitis 10.1
21 choreatic disease 10.1
22 sensory peripheral neuropathy 10.1
23 retinitis 10.1
24 movement disease 10.1
25 dystonia 10.1
26 peripheral nervous system disease 10.1
27 basal ganglia disease 10.1
28 neuropathy 10.1
29 hypertrophic cardiomyopathy 10.1
30 hypotonia 10.1
31 spasticity 10.1
32 optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy 10.0
33 branchiootic syndrome 1 10.0
34 mitochondrial complex v deficiency, nuclear type 1 10.0
35 helix syndrome 10.0
36 exanthem 10.0
37 leukemia 10.0
38 acute leukemia 10.0
39 post-traumatic stress disorder 10.0
40 adenocarcinoma 10.0
41 ischemia 10.0
42 acute stress disorder 10.0
43 influenza 10.0
44 back pain 10.0
45 lymphedema 10.0
46 gaucher disease, type iii 10.0 MT-CO3 MT-CO2
47 osteogenic sarcoma 10.0
48 mitochondrial complex v deficiency, mitochondrial type 1 10.0
49 infantile apnea 10.0
50 mitochondrial myopathy 9.8 MT-CO3 MT-CO2 MT-ATP8 MT-ATP6

Graphical network of the top 20 diseases related to Mitochondrial Dna-Associated Leigh Syndrome:



Diseases related to Mitochondrial Dna-Associated Leigh Syndrome

Symptoms & Phenotypes for Mitochondrial Dna-Associated Leigh Syndrome

Human phenotypes related to Mitochondrial Dna-Associated Leigh Syndrome:

32 (show all 49)
# Description HPO Frequency HPO Source Accession
1 increased csf lactate 32 hallmark (90%) HP:0002490
2 abnormality of krebs cycle metabolism 32 hallmark (90%) HP:0000816
3 spasticity 32 frequent (33%) HP:0001257
4 muscle weakness 32 frequent (33%) HP:0001324
5 failure to thrive 32 frequent (33%) HP:0001508
6 chorea 32 frequent (33%) HP:0002072
7 dyskinesia 32 frequent (33%) HP:0100660
8 generalized myoclonic seizures 32 frequent (33%) HP:0002123
9 severe global developmental delay 32 frequent (33%) HP:0011344
10 gait ataxia 32 frequent (33%) HP:0002066
11 dystonia 32 frequent (33%) HP:0001332
12 ophthalmoparesis 32 frequent (33%) HP:0000597
13 generalized tonic-clonic seizures 32 frequent (33%) HP:0002069
14 increased serum lactate 32 frequent (33%) HP:0002151
15 sensorimotor neuropathy 32 frequent (33%) HP:0007141
16 infantile muscular hypotonia 32 frequent (33%) HP:0008947
17 episodic vomiting 32 frequent (33%) HP:0002572
18 pigmentary retinopathy 32 frequent (33%) HP:0000580
19 lacticaciduria 32 frequent (33%) HP:0003648
20 focal t2 hyperintense basal ganglia lesion 32 frequent (33%) HP:0007183
21 nystagmus 32 occasional (7.5%) HP:0000639
22 hyperreflexia 32 occasional (7.5%) HP:0001347
23 dysphagia 32 occasional (7.5%) HP:0002015
24 hypothermia 32 occasional (7.5%) HP:0002045
25 developmental regression 32 occasional (7.5%) HP:0002376
26 hepatomegaly 32 occasional (7.5%) HP:0002240
27 sensorineural hearing impairment 32 occasional (7.5%) HP:0000407
28 optic atrophy 32 occasional (7.5%) HP:0000648
29 fever 32 occasional (7.5%) HP:0001945
30 hypertrophic cardiomyopathy 32 occasional (7.5%) HP:0001639
31 dilated cardiomyopathy 32 occasional (7.5%) HP:0001644
32 apnea 32 occasional (7.5%) HP:0002104
33 mitochondrial myopathy 32 occasional (7.5%) HP:0003737
34 bulbar signs 32 occasional (7.5%) HP:0002483
35 hepatic failure 32 occasional (7.5%) HP:0001399
36 hyporeflexia 32 occasional (7.5%) HP:0001265
37 rod-cone dystrophy 32 occasional (7.5%) HP:0000510
38 infantile spasms 32 occasional (7.5%) HP:0012469
39 hyperalaninemia 32 occasional (7.5%) HP:0003348
40 episodic respiratory distress 32 occasional (7.5%) HP:0004885
41 demyelinating peripheral neuropathy 32 occasional (7.5%) HP:0007108
42 segmental peripheral demyelination/remyelination 32 occasional (7.5%) HP:0003481
43 hyperventilation 32 occasional (7.5%) HP:0002883
44 abnormal speech prosody 32 occasional (7.5%) HP:0031434
45 cardiac conduction abnormality 32 occasional (7.5%) HP:0031546
46 multiple glomerular cysts 32 occasional (7.5%) HP:0100611
47 abnormal renal tubule morphology 32 occasional (7.5%) HP:0000091
48 ragged-red muscle fibers 32 very rare (1%) HP:0003200
49 low plasma citrulline 32 very rare (1%) HP:0003572

Drugs & Therapeutics for Mitochondrial Dna-Associated Leigh Syndrome

Drugs for Mitochondrial Dna-Associated Leigh Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 19)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Sargramostim Approved, Investigational Phase 2 83869-56-1, 123774-72-1
2
Melphalan Approved Phase 1, Phase 2 148-82-3 460612 4053
3
Tadalafil Approved, Investigational Phase 2 171596-29-5 110635
4
Lenalidomide Approved Phase 2 191732-72-6 216326
5 Alkylating Agents Phase 1, Phase 2
6 Immunosuppressive Agents Phase 1, Phase 2
7 Antineoplastic Agents, Alkylating Phase 1, Phase 2
8 Immunologic Factors Phase 2
9 Angiogenesis Inhibitors Phase 2
10 Heptavalent Pneumococcal Conjugate Vaccine Phase 2
11 Phosphodiesterase Inhibitors Phase 2
12 Angiogenesis Modulating Agents Phase 2
13 Phosphodiesterase 5 Inhibitors Phase 2
14 Vasodilator Agents Phase 2
15 Vaccines Phase 2
16
Cyclophosphamide Approved, Investigational Phase 1 50-18-0, 6055-19-2 2907
17 Antirheumatic Agents Phase 1
18 Liver Extracts
19 Ubiquinone

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Randomized Trial of Activated Marrow Infiltrating Lymphocytes Alone or in Conjunction With an Allogeneic GM-CSF-based Myeloma Cellular Vaccine in the Autologous Transplant Setting in Multiple Myeloma Unknown status NCT01045460 Phase 2
2 Empowering Daughters and Mother-in-laws to Mitigate Gender-based Violence and Promote Women's Health in India Completed NCT01337778 Phase 2
3 Adoptive Immunotherapy Utilizing Activated Marrow Infiltrating Lymphocytes in the Autologous Transplant Setting in Multiple Myeloma Completed NCT00566098 Phase 1, Phase 2 Melphalan
4 Randomized Phase II Study of Autologous Stem Cell Transplantation With Tadalafil and Lenalidomide Maintenance With or Without Activated Marrow Infiltrating Lymphocytes (MILs) in High Risk Myeloma Recruiting NCT01858558 Phase 2 No aMIL
5 Adoptive Immunotherapy Utilizing Activated Marrow Infiltrating Lymphocytes Derived From Patients With Bone Marrow Relapse of Hematologic Malignancies After Allogeneic Hematopoietic Cell Transplantation Using Post-Transplantation Cyclophosphamide Graft-Versus-Host Disease Prophylaxis. Active, not recruiting NCT02342613 Phase 1
6 Minimally Invasive Liver Surgery for Metastases From Colorectal Cancer: Oncologic Outcome and Prognostic Factors Completed NCT01356706
7 Comparison of the McGrath Videolaryngoscope and the Pentax-AWS With the Macintosh Laryngoscope for Nasotracheal Intubation in Patients With Manual In-line Stabilization Completed NCT02647606
8 North American Mitochondrial Disease Consortium Patient Registry and Biorepository (NAMDC) Recruiting NCT01694940

Search NIH Clinical Center for Mitochondrial Dna-Associated Leigh Syndrome

Genetic Tests for Mitochondrial Dna-Associated Leigh Syndrome

Anatomical Context for Mitochondrial Dna-Associated Leigh Syndrome

MalaCards organs/tissues related to Mitochondrial Dna-Associated Leigh Syndrome:

41
Brain, Heart, Kidney, Liver, Bone, Bone Marrow

Publications for Mitochondrial Dna-Associated Leigh Syndrome

Articles related to Mitochondrial Dna-Associated Leigh Syndrome:

(show all 28)
# Title Authors PMID Year
1
Deregulating mitochondrial metabolite and ion transport has beneficial effects in yeast and human cellular models for NARP syndrome. 38
31276579 2019
2
Sleep and circadian defects in a Drosophila model of mitochondrial encephalomyopathy. 38
30868108 2019
3
Epilepsy in Leigh Syndrome With Mitochondrial DNA Mutations. 38
31139141 2019
4
Phenotypic spectrum of maternally inherited Leigh Syndrome associated with the m.8993T>G variant. 38
30023306 2018
5
Novel insights into the functional metabolic impact of an apparent de novo m.8993T>G variant in the MT-ATP6 gene associated with maternally inherited form of Leigh Syndrome. 38
29602698 2018
6
Alleviation of neuronal energy deficiency by mTOR inhibition as a treatment for mitochondria-related neurodegeneration. 38
27008180 2016
7
Whole mitochondrial genome analysis of a family with NARP/MILS caused by m.8993T>C mutation in the MT-ATP6 gene. 38
22819295 2012
8
Mitochondrial DNA mutations provoke dominant inhibition of mitochondrial inner membrane fusion. 38
23166736 2012
9
Low citrulline in Leigh disease: still a biomarker of maternally inherited Leigh syndrome. 38
20472868 2010
10
Maternally inherited Leigh syndrome: an unusual cause of infantile apnea. 38
19669818 2010
11
Parkin overexpression selects against a deleterious mtDNA mutation in heteroplasmic cybrid cells. 38
20547844 2010
12
Leigh disease presenting in utero due to a novel missense mutation in the mitochondrial DNA-ND3. 38
20202874 2010
13
Human NARP mitochondrial mutation metabolism corrected with alpha-ketoglutarate/aspartate: a potential new therapy. 38
19667215 2009
14
Maternally inherited Leigh syndrome: T8993G mutation in a Tunisian family. 38
19433277 2009
15
Biochemical consequences in yeast of the human mitochondrial DNA 8993T>C mutation in the ATPase6 gene found in NARP/MILS patients. 38
19269308 2009
16
A yeast model of the neurogenic ataxia retinitis pigmentosa (NARP) T8993G mutation in the mitochondrial ATP synthase-6 gene. 38
17855363 2007
17
Long-term outcome of Leigh syndrome caused by the NARP-T8993C mtDNA mutation. 38
17663470 2007
18
Genetic, pathogenetic, and phenotypic implications of the mitochondrial A3243G tRNALeu(UUR) mutation. 38
17587249 2007
19
ATP6 homoplasmic mutations inhibit and destabilize the human F1F0-ATP synthase without preventing enzyme assembly and oligomerization. 38
17121862 2007
20
Maternally-inherited Leigh syndrome-related mutations bolster mitochondrial-mediated apoptosis. 38
15228605 2004
21
Mitochondrial DNA-Associated Leigh Syndrome and NARP 38
20301352 2003
22
Rescue of a deficiency in ATP synthesis by transfer of MTATP6, a mitochondrial DNA-encoded gene, to the nucleus. 38
11925565 2002
23
[Maternally inherited Leigh syndrome]. 38
12013906 2002
24
Pathogenesis of primary defects in mitochondrial ATP synthesis. 38
11735378 2001
25
G8363A mutation in the mitochondrial DNA transfer ribonucleic acidLys gene: another cause of Leigh syndrome. 38
11108511 2000
26
Human mitochondrial diseases: answering questions and questioning answers. 38
9770297 1999
27
Clinical heterogeneity associated with the mitochondrial DNA T8993C point mutation. 38
8726250 1996
28
Maternally inherited Leigh syndrome. 38
8095070 1993

Variations for Mitochondrial Dna-Associated Leigh Syndrome

Expression for Mitochondrial Dna-Associated Leigh Syndrome

Search GEO for disease gene expression data for Mitochondrial Dna-Associated Leigh Syndrome.

Pathways for Mitochondrial Dna-Associated Leigh Syndrome

GO Terms for Mitochondrial Dna-Associated Leigh Syndrome

Cellular components related to Mitochondrial Dna-Associated Leigh Syndrome according to GeneCards Suite gene sharing:

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.61 SURF1 SDHA MT-ND3 MT-CO3 MT-CO2 MT-ATP8
2 respiratory chain GO:0070469 9.58 MT-ND4L MT-ND3 MT-CO2
3 mitochondrial membrane GO:0031966 9.55 MT-ND4L MT-ND3 MT-ATP8 COX15 COX10
4 mitochondrial respiratory chain complex I GO:0005747 9.52 MT-ND4L MT-ND3
5 mitochondrial proton-transporting ATP synthase complex GO:0005753 9.51 MT-ATP8 MT-ATP6
6 mitochondrial respiratory chain GO:0005746 9.49 SURF1 COX15
7 proton-transporting ATP synthase complex, coupling factor F(o) GO:0045263 9.48 MT-ATP8 MT-ATP6
8 respiratory chain complex IV GO:0045277 9.46 MT-CO3 MT-CO2
9 cytochrome complex GO:0070069 9.32 COX15 COX10
10 mitochondrial inner membrane GO:0005743 9.32 SURF1 SDHA MT-ND3 MT-CO3 MT-CO2 MT-ATP8
11 NADH dehydrogenase complex GO:0030964 9.26 MT-ND4L MT-ND3
12 membrane GO:0016020 10.17 SURF1 SDHA MT-ND4L MT-ND3 MT-CO3 MT-CO2
13 integral component of membrane GO:0016021 10.07 SURF1 MT-ND4L MT-ND3 MT-CO3 MT-CO2 MT-ATP8

Biological processes related to Mitochondrial Dna-Associated Leigh Syndrome according to GeneCards Suite gene sharing:

(show all 18)
# Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.73 SURF1 SDHA MT-ND4L MT-ND3 MT-CO2 COX15
2 electron transport chain GO:0022900 9.63 SURF1 SDHA MT-CO2
3 mitochondrial respiratory chain complex I assembly GO:0032981 9.58 MT-ND3 BCS1L
4 aerobic respiration GO:0009060 9.58 SURF1 MT-CO3 COX10
5 mitochondrial electron transport, NADH to ubiquinone GO:0006120 9.57 MT-ND4L MT-ND3
6 cristae formation GO:0042407 9.56 MT-ATP8 MT-ATP6
7 cellular respiration GO:0045333 9.55 COX15 COX10
8 proton transmembrane transport GO:1902600 9.55 SURF1 MT-CO3 MT-CO2 COX15 COX10
9 heme biosynthetic process GO:0006783 9.54 COX15 COX10
10 mitochondrial respiratory chain complex IV assembly GO:0033617 9.52 SURF1 BCS1L
11 ATP synthesis coupled proton transport GO:0015986 9.51 MT-ATP8 MT-ATP6
12 respiratory electron transport chain GO:0022904 9.49 SDHA MT-CO3
13 mitochondrial ATP synthesis coupled proton transport GO:0042776 9.48 MT-ATP8 MT-ATP6
14 ATP synthesis coupled electron transport GO:0042773 9.43 MT-ND4L MT-CO2
15 heme a biosynthetic process GO:0006784 9.37 COX15 COX10
16 ATP biosynthetic process GO:0006754 9.32 MT-ATP8 MT-ATP6
17 mitochondrial electron transport, cytochrome c to oxygen GO:0006123 9.26 MT-CO3 MT-CO2 COX15 COX10
18 respiratory chain complex IV assembly GO:0008535 8.92 SURF1 MT-CO3 COX15 COX10

Molecular functions related to Mitochondrial Dna-Associated Leigh Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity GO:0016491 9.43 SDHA MT-ND4L MT-CO2
2 NADH dehydrogenase (ubiquinone) activity GO:0008137 9.32 MT-ND4L MT-ND3
3 proton transmembrane transporter activity GO:0015078 9.16 MT-ATP8 MT-ATP6
4 cytochrome-c oxidase activity GO:0004129 9.02 SURF1 MT-CO3 MT-CO2 COX15 COX10
5 oxidoreductase activity, acting on the CH-CH group of donors GO:0016627 8.96 SDHA COX15

Sources for Mitochondrial Dna-Associated Leigh Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 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 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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