MILS
MCID: MTC112
MIFTS: 37

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 52
Maternally Inherited Leigh Syndrome 52 71
Subacute Necrotizing Encephalomyelopathy Maternally Inherited 52
Leigh Disease, Maternally Inherited 52
Mils 52

Classifications:



Summaries for Mitochondrial Dna-Associated Leigh Syndrome

NIH Rare Diseases : 52 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 mitochondrial dna-associated leigh syndrome and narp and leigh syndrome. 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 Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. and AMPK Enzyme Complex Pathway. The drugs Lenalidomide and Tadalafil 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 68)
# Related Disease Score Top Affiliating Genes
1 mitochondrial dna-associated leigh syndrome and narp 31.7 SURF1 SDHA MT-ATP6 COX15 COX10 BCS1L
2 leigh syndrome 30.9 SURF1 SDHA MT-ATP6 COX15 COX10 BCS1L
3 hypertrophic cardiomyopathy 29.1 MT-ATP6 COX15 COX10
4 lactic acidosis 29.0 SURF1 MT-ATP6 COX15 BCS1L
5 neuropathy, ataxia, and retinitis pigmentosa 28.9 SURF1 MT-ATP6 COX15 COX10
6 mitochondrial metabolism disease 27.3 SURF1 SDHA MT-ATP6 COX15 COX10 BCS1L
7 cholestasis, benign recurrent intrahepatic, 2 11.3
8 traumatic brain injury 10.4
9 brain injury 10.3
10 liver disease 10.3
11 posttransplant acute limbic encephalitis 10.2
12 mitochondrial disorders 10.2
13 encephalopathy 10.2
14 retinitis pigmentosa 10.1
15 ataxia and polyneuropathy, adult-onset 10.1
16 chorea, childhood-onset, with psychomotor retardation 10.1
17 neuroretinitis 10.1
18 choreatic disease 10.1
19 sensory peripheral neuropathy 10.1
20 retinitis 10.1
21 movement disease 10.1
22 dystonia 10.1
23 peripheral nervous system disease 10.1
24 basal ganglia disease 10.1
25 neuropathy 10.1
26 hypotonia 10.1
27 spasticity 10.1
28 optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy 10.0
29 branchiootic syndrome 1 10.0
30 macular degeneration, age-related, 1 10.0
31 mitochondrial complex v deficiency, nuclear type 1 10.0
32 helix syndrome 10.0
33 exanthem 10.0
34 hereditary lymphedema i 10.0
35 non-alcoholic fatty liver disease 10.0
36 leukemia 10.0
37 acute leukemia 10.0
38 post-traumatic stress disorder 10.0
39 adenocarcinoma 10.0
40 ischemia 10.0
41 macular retinal edema 10.0
42 acute stress disorder 10.0
43 end stage renal disease 10.0
44 influenza 10.0
45 diabetic macular edema 10.0
46 fatty liver disease 10.0
47 back pain 10.0
48 osteogenic sarcoma 10.0
49 mitochondrial complex v deficiency, mitochondrial type 1 10.0
50 infantile apnea 10.0

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:

31 (show all 49)
# Description HPO Frequency HPO Source Accession
1 increased csf lactate 31 hallmark (90%) HP:0002490
2 abnormality of krebs cycle metabolism 31 hallmark (90%) HP:0000816
3 dyskinesia 31 frequent (33%) HP:0100660
4 muscle weakness 31 frequent (33%) HP:0001324
5 failure to thrive 31 frequent (33%) HP:0001508
6 spasticity 31 frequent (33%) HP:0001257
7 increased serum lactate 31 frequent (33%) HP:0002151
8 dystonia 31 frequent (33%) HP:0001332
9 chorea 31 frequent (33%) HP:0002072
10 severe global developmental delay 31 frequent (33%) HP:0011344
11 ophthalmoparesis 31 frequent (33%) HP:0000597
12 gait ataxia 31 frequent (33%) HP:0002066
13 pigmentary retinopathy 31 frequent (33%) HP:0000580
14 infantile muscular hypotonia 31 frequent (33%) HP:0008947
15 sensorimotor neuropathy 31 frequent (33%) HP:0007141
16 episodic vomiting 31 frequent (33%) HP:0002572
17 focal t2 hyperintense basal ganglia lesion 31 frequent (33%) HP:0007183
18 lacticaciduria 31 frequent (33%) HP:0003648
19 bilateral tonic-clonic seizure 31 frequent (33%) HP:0002069
20 generalized myoclonic seizure 31 frequent (33%) HP:0002123
21 hepatomegaly 31 occasional (7.5%) HP:0002240
22 sensorineural hearing impairment 31 occasional (7.5%) HP:0000407
23 optic atrophy 31 occasional (7.5%) HP:0000648
24 developmental regression 31 occasional (7.5%) HP:0002376
25 fever 31 occasional (7.5%) HP:0001945
26 hypertrophic cardiomyopathy 31 occasional (7.5%) HP:0001639
27 dysphagia 31 occasional (7.5%) HP:0002015
28 nystagmus 31 occasional (7.5%) HP:0000639
29 hyperreflexia 31 occasional (7.5%) HP:0001347
30 dilated cardiomyopathy 31 occasional (7.5%) HP:0001644
31 bulbar signs 31 occasional (7.5%) HP:0002483
32 apnea 31 occasional (7.5%) HP:0002104
33 hepatic failure 31 occasional (7.5%) HP:0001399
34 hyporeflexia 31 occasional (7.5%) HP:0001265
35 infantile spasms 31 occasional (7.5%) HP:0012469
36 rod-cone dystrophy 31 occasional (7.5%) HP:0000510
37 hypothermia 31 occasional (7.5%) HP:0002045
38 mitochondrial myopathy 31 occasional (7.5%) HP:0003737
39 demyelinating peripheral neuropathy 31 occasional (7.5%) HP:0007108
40 hyperalaninemia 31 occasional (7.5%) HP:0003348
41 hyperventilation 31 occasional (7.5%) HP:0002883
42 segmental peripheral demyelination/remyelination 31 occasional (7.5%) HP:0003481
43 cardiac conduction abnormality 31 occasional (7.5%) HP:0031546
44 episodic respiratory distress 31 occasional (7.5%) HP:0004885
45 abnormal speech prosody 31 occasional (7.5%) HP:0031434
46 multiple glomerular cysts 31 occasional (7.5%) HP:0100611
47 abnormal renal tubule morphology 31 occasional (7.5%) HP:0000091
48 ragged-red muscle fibers 31 very rare (1%) HP:0003200
49 low plasma citrulline 31 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 18)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Lenalidomide Approved Phase 2 191732-72-6 216326
2
Tadalafil Approved, Investigational Phase 2 171596-29-5 110635
3
nivolumab Approved Phase 2 946414-94-4
4
Cyclophosphamide Approved, Investigational Phase 2 50-18-0, 6055-19-2 2907
5
Melphalan Approved Phase 2 148-82-3 460612 4053
6
Lenograstim Approved, Investigational Phase 2 135968-09-1
7
Sargramostim Approved, Investigational Phase 2 83869-56-1, 123774-72-1
8 Molgramostim Investigational Phase 2 99283-10-0
9 Heptavalent Pneumococcal Conjugate Vaccine Phase 1, Phase 2
10 Antineoplastic Agents, Immunological Phase 2
11 Immunologic Factors Phase 2
12 Alkylating Agents Phase 2
13 Vaccines Phase 2
14 Immunosuppressive Agents Phase 2
15 Antirheumatic Agents Phase 2
16
Coenzyme Q10 Approved, Investigational, Nutraceutical 303-98-0 5281915
17 Liver Extracts
18 Ubiquinone

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 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 Completed NCT01858558 Phase 2 No aMIL
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 A Phase 2a, Open-Label, Multi-Center Study to Assess the Efficacy and Safety of Marrow Infiltrating Lymphocytes - Non-Small Cell Lung Cancer (MILs™ - NSCLC) Alone or in Combination With Nivolumab in Subjects With Locally Advanced and Unresectable or Metastatic NSCLC Previously Treated With Anti-PD-1 Recruiting NCT04069936 Phase 2
5 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 Active, not recruiting NCT01045460 Phase 2 Cyclophosphamide;Melphalan
6 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. Recruiting NCT02342613 Phase 1
7 Minimally Invasive Liver Surgery for Metastases From Colorectal Cancer: Oncologic Outcome and Prognostic Factors Completed NCT01356706
8 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
9 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:

40
Brain, Heart, Kidney, Liver, Bone Marrow, Bone, Lung

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. 61
31276579 2019
2
Sleep and circadian defects in a Drosophila model of mitochondrial encephalomyopathy. 61
30868108 2019
3
Epilepsy in Leigh Syndrome With Mitochondrial DNA Mutations. 61
31139141 2019
4
Phenotypic spectrum of maternally inherited Leigh Syndrome associated with the m.8993T>G variant. 61
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. 61
29602698 2018
6
Alleviation of neuronal energy deficiency by mTOR inhibition as a treatment for mitochondria-related neurodegeneration. 61
27008180 2016
7
Whole mitochondrial genome analysis of a family with NARP/MILS caused by m.8993T>C mutation in the MT-ATP6 gene. 61
22819295 2012
8
Mitochondrial DNA mutations provoke dominant inhibition of mitochondrial inner membrane fusion. 61
23166736 2012
9
Low citrulline in Leigh disease: still a biomarker of maternally inherited Leigh syndrome. 61
20472868 2010
10
Maternally inherited Leigh syndrome: an unusual cause of infantile apnea. 61
19669818 2010
11
Parkin overexpression selects against a deleterious mtDNA mutation in heteroplasmic cybrid cells. 61
20547844 2010
12
Leigh disease presenting in utero due to a novel missense mutation in the mitochondrial DNA-ND3. 61
20202874 2010
13
Human NARP mitochondrial mutation metabolism corrected with alpha-ketoglutarate/aspartate: a potential new therapy. 61
19667215 2009
14
Maternally inherited Leigh syndrome: T8993G mutation in a Tunisian family. 61
19433277 2009
15
Biochemical consequences in yeast of the human mitochondrial DNA 8993T>C mutation in the ATPase6 gene found in NARP/MILS patients. 61
19269308 2009
16
A yeast model of the neurogenic ataxia retinitis pigmentosa (NARP) T8993G mutation in the mitochondrial ATP synthase-6 gene. 61
17855363 2007
17
Long-term outcome of Leigh syndrome caused by the NARP-T8993C mtDNA mutation. 61
17663470 2007
18
Genetic, pathogenetic, and phenotypic implications of the mitochondrial A3243G tRNALeu(UUR) mutation. 61
17587249 2007
19
ATP6 homoplasmic mutations inhibit and destabilize the human F1F0-ATP synthase without preventing enzyme assembly and oligomerization. 61
17121862 2007
20
Maternally-inherited Leigh syndrome-related mutations bolster mitochondrial-mediated apoptosis. 61
15228605 2004
21
Mitochondrial DNA-Associated Leigh Syndrome and NARP 61
20301352 2003
22
Rescue of a deficiency in ATP synthesis by transfer of MTATP6, a mitochondrial DNA-encoded gene, to the nucleus. 61
11925565 2002
23
[Maternally inherited Leigh syndrome]. 61
12013906 2002
24
Pathogenesis of primary defects in mitochondrial ATP synthesis. 61
11735378 2001
25
G8363A mutation in the mitochondrial DNA transfer ribonucleic acidLys gene: another cause of Leigh syndrome. 61
11108511 2000
26
Human mitochondrial diseases: answering questions and questioning answers. 61
9770297 1999
27
Clinical heterogeneity associated with the mitochondrial DNA T8993C point mutation. 61
8726250 1996
28
Maternally inherited Leigh syndrome. 61
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:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.43 SURF1 SDHA MT-ATP6 COX15 COX10 BCS1L
2 mitochondrial membrane GO:0031966 9.32 COX15 COX10
3 mitochondrial respiratory chain GO:0005746 9.26 SURF1 COX15
4 cytochrome complex GO:0070069 9.16 COX15 COX10
5 mitochondrial inner membrane GO:0005743 9.1 SURF1 SDHA MT-ATP6 COX15 COX10 BCS1L

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

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.67 SURF1 SDHA COX15
2 mitochondrion organization GO:0007005 9.48 COX10 BCS1L
3 electron transport chain GO:0022900 9.46 SURF1 SDHA
4 aerobic respiration GO:0009060 9.43 SURF1 COX10
5 mitochondrial respiratory chain complex IV assembly GO:0033617 9.4 SURF1 BCS1L
6 heme biosynthetic process GO:0006783 9.37 COX15 COX10
7 proton transmembrane transport GO:1902600 9.33 SURF1 COX15 COX10
8 mitochondrial electron transport, cytochrome c to oxygen GO:0006123 9.32 COX15 COX10
9 cellular respiration GO:0045333 9.26 COX15 COX10
10 heme a biosynthetic process GO:0006784 8.96 COX15 COX10
11 respiratory chain complex IV assembly GO:0008535 8.8 SURF1 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, acting on the CH-CH group of donors GO:0016627 8.96 SDHA COX15
2 cytochrome-c oxidase activity GO:0004129 8.8 SURF1 COX15 COX10

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 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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