MMDS
MCID: MLT027
MIFTS: 37

Multiple Mitochondrial Dysfunctions Syndrome (MMDS)

Categories: Eye diseases, Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases, Respiratory diseases

Aliases & Classifications for Multiple Mitochondrial Dysfunctions Syndrome

MalaCards integrated aliases for Multiple Mitochondrial Dysfunctions Syndrome:

Name: Multiple Mitochondrial Dysfunctions Syndrome 12 20 43 58 36 29 6 44 15 70
Fatal Multiple Mitochondrial Dysfunction Syndrome 12 20
Fatal Multiple Mitochondrial Dysfunctions Syndrome 20
Multiple Mitochondrial Dysfunctions Syndrome 1 70
Mitochondrial Dysfunctions, Multiple, Syndrome 39
Multiple Mitochondrial Dysfunction Syndrome 43
Mmds 43

Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


External Ids:

Disease Ontology 12 DOID:0070330
KEGG 36 H01894
MeSH 44 C565304
Orphanet 58 ORPHA289573
UMLS 70 C3276432 C3502075

Summaries for Multiple Mitochondrial Dysfunctions Syndrome

MedlinePlus Genetics : 43 Multiple mitochondrial dysfunctions syndrome is characterized by impairment of cellular structures called mitochondria, which are the energy-producing centers of cells. While certain mitochondrial disorders are caused by impairment of a single stage of energy production, individuals with multiple mitochondrial dysfunctions syndrome have reduced function of more than one stage. The signs and symptoms of this severe condition begin early in life, and affected individuals usually do not live past infancy.Affected infants typically have severe brain dysfunction (encephalopathy), which can contribute to weak muscle tone (hypotonia), seizures, and delayed development of mental and movement abilities (psychomotor delay). These infants often have difficulty growing and gaining weight at the expected rate (failure to thrive). Most affected babies have a buildup of a chemical called lactic acid in the body (lactic acidosis), which can be life-threatening. They may also have high levels of a molecule called glycine (hyperglycinemia) or elevated levels of sugar (hyperglycemia) in the blood. Some babies with multiple mitochondrial dysfunctions syndrome have high blood pressure in the blood vessels that connect to the lungs (pulmonary hypertension) or weakening of the heart muscle (cardiomyopathy).

MalaCards based summary : Multiple Mitochondrial Dysfunctions Syndrome, also known as fatal multiple mitochondrial dysfunction syndrome, is related to multiple mitochondrial dysfunctions syndrome 4 and multiple mitochondrial dysfunctions syndrome 1, and has symptoms including lethargy and weakness. An important gene associated with Multiple Mitochondrial Dysfunctions Syndrome is ISCA1 (Iron-Sulfur Cluster Assembly 1), and among its related pathways/superpathways is Mitochondrial iron-sulfur cluster biogenesis. The drugs Midazolam and Dexmedetomidine have been mentioned in the context of this disorder.

Disease Ontology : 12 A mitochondrial metabolism disease that is characterized by reduced function of more than one stage of of energy production resulting from mitochondria impairment.

GARD : 20 Multiple mitochondrial dysfunctions syndrome (MMDS) is a severe condition that affects the energy-producing structures of cells (called the mitochondria ). Signs and symptoms of this condition generally develop early in life and may include encephalopathy, hypotonia (poor muscle tone), seizures, developmental delay, failure to thrive, lactic acidosis and a variety of other health problems. Due to the severity of the condition, most affected babies do not live past infancy. MMDS can be caused by changes ( mutations ) in the NFU1 gene or the BOLA3 gene. In these cases, the condition is inherited in an autosomal recessive manner. Treatment is based on the signs and symptoms present in each person.

KEGG : 36 Multiple mitochondrial dysfunctions syndrome (MMDS) is a severe autosomal recessive disease with onset in early infancy. Pathogenic variations in genes encoding several components of the Fe-S cluster biogenesis machinery are already implicated in causing five types of MMDS. All MMDS share variable neurodevelopmental delay, regression, seizures, lactic acidosis and leukodystrophy resulting in early death of affected individuals.

Related Diseases for Multiple Mitochondrial Dysfunctions Syndrome

Diseases in the Multiple Mitochondrial Dysfunctions Syndrome family:

Multiple Mitochondrial Dysfunctions Syndrome 1 Multiple Mitochondrial Dysfunctions Syndrome 3
Multiple Mitochondrial Dysfunctions Syndrome 4 Multiple Mitochondrial Dysfunctions Syndrome 5
Multiple Mitochondrial Dysfunctions Syndrome 6 Isca1-Related Multiple Mitochondrial Dysfunctions Syndrome

Diseases related to Multiple Mitochondrial Dysfunctions Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 35)
# Related Disease Score Top Affiliating Genes
1 multiple mitochondrial dysfunctions syndrome 4 32.1 NFU1 LIAS ISCA2 ISCA1 IBA57 BOLA3
2 multiple mitochondrial dysfunctions syndrome 1 31.6 NFU1 LIAS ISCU IBA57 FDX2 BOLA3
3 multiple mitochondrial dysfunctions syndrome 2 with hyperglycinemia 31.3 NUBPL NFU1 LIAS ISCA2 ISCA1 IBA57
4 multiple mitochondrial dysfunctions syndrome 3 31.0 NUBPL NFU1 LIAS ISCA2 ISCA1 IBA57
5 lactic acidosis 28.9 NFU1 LIAS ISCU ISCA2 ISCA1 IBA57
6 leukodystrophy 28.7 NUBPL NFU1 ISCA2 ISCA1 IBA57 GLRX5
7 multiple mitochondrial dysfunctions syndrome 5 11.9
8 multiple mitochondrial dysfunctions syndrome 6 11.9
9 isca1-related multiple mitochondrial dysfunctions syndrome 11.5
10 isca2-related mitochondrial disorder 11.3
11 pathologic nystagmus 10.1
12 dihydrolipoamide dehydrogenase deficiency 10.0
13 3-methylglutaconic aciduria, type iii 10.0
14 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.0
15 pulmonary hypertension 10.0
16 sensorineural hearing loss 10.0
17 constipation 10.0
18 mitochondrial encephalomyopathy 10.0
19 sideroblastic anemia 10.0
20 pachygyria 10.0
21 hypotonia 10.0
22 spasticity 10.0
23 autosomal recessive disease 9.9
24 mood disorder 9.9
25 mild cognitive impairment 9.9
26 respiratory failure 9.9
27 encephalopathy 9.9
28 disorder of energy metabolism 9.9
29 mitochondrial metabolism disease 9.9 NFU1 BOLA3
30 lipoic acid biosynthesis defects 9.7 NFU1 LIAS GLRX5 BOLA3
31 pyruvate dehydrogenase e1-alpha deficiency 9.6 NFU1 LIAS IBA57 BOLA3
32 anemia, sideroblastic, and spinocerebellar ataxia 9.4 NFU1 ISCU ISCA2 ISCA1 GLRX5
33 anemia, sideroblastic, 1 9.4 ISCU ISCA2 ISCA1 IBA57 GLRX5
34 combined oxidative phosphorylation deficiency 19 8.8 NUBPL ISCU ISCA2 IBA57 GLRX5 FDX2
35 glycine encephalopathy 8.5 NUBPL NFU1 LIAS ISCA2 ISCA1 IBA57

Graphical network of the top 20 diseases related to Multiple Mitochondrial Dysfunctions Syndrome:



Diseases related to Multiple Mitochondrial Dysfunctions Syndrome

Symptoms & Phenotypes for Multiple Mitochondrial Dysfunctions Syndrome

UMLS symptoms related to Multiple Mitochondrial Dysfunctions Syndrome:


lethargy; weakness

Drugs & Therapeutics for Multiple Mitochondrial Dysfunctions Syndrome

Drugs for Multiple Mitochondrial Dysfunctions Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 52)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Midazolam Approved, Illicit Phase 4 59467-70-8 4192
2
Dexmedetomidine Approved, Vet_approved Phase 4 113775-47-6 5311068 68602
3
Propofol Approved, Investigational, Vet_approved Phase 4 2078-54-8 4943
4
Meperidine Approved Phase 4 57-42-1 4058
5 Narcotics Phase 4
6 Analgesics, Opioid Phase 4
7 Analgesics Phase 4
8 Adrenergic alpha-Agonists Phase 4
9 Adrenergic Agonists Phase 4
10 Psychotropic Drugs Phase 4
11 Analgesics, Non-Narcotic Phase 4
12 Hypnotics and Sedatives Phase 4
13 Anesthetics Phase 4
14 Neurotransmitter Agents Phase 4
15 GABA Modulators Phase 4
16 Adrenergic Agents Phase 4
17 Anesthetics, Intravenous Phase 4
18 Anesthetics, General Phase 4
19 Anti-Anxiety Agents Phase 4
20
Etoposide Approved Phase 2, Phase 3 33419-42-0 36462
21
Fludarabine Approved Phase 2, Phase 3 21679-14-1, 75607-67-9 30751
22
Treosulfan Approved, Investigational Phase 2, Phase 3 299-75-2 9296
23
Thiotepa Approved, Investigational Phase 2, Phase 3 52-24-4 5453
24
Mesna Approved, Investigational Phase 2, Phase 3 3375-50-6 598
25
Busulfan Approved, Investigational Phase 2, Phase 3 55-98-1 2478
26
Ibuprofen Approved Phase 2, Phase 3 15687-27-1 3672
27
Cyclophosphamide Approved, Investigational Phase 2, Phase 3 50-18-0, 6055-19-2 2907
28 Muromonab-CD3 Phase 3
29 Etoposide phosphate Phase 2, Phase 3
30 Immunosuppressive Agents Phase 2, Phase 3
31 Immunologic Factors Phase 2, Phase 3
32 Alkylating Agents Phase 2, Phase 3
33 Immunoglobulins, Intravenous Phase 2, Phase 3
34 Antirheumatic Agents Phase 2, Phase 3
35 Immunoglobulins Phase 2, Phase 3
36 Thymoglobulin Phase 2, Phase 3
37 Antibodies Phase 2, Phase 3
38 Antilymphocyte Serum Phase 2, Phase 3
39
Ethanol Approved Phase 2 64-17-5 702
40
Naltrexone Approved, Investigational, Vet_approved Phase 2 16590-41-3 5360515
41
Buprenorphine Approved, Illicit, Investigational, Vet_approved Phase 2 52485-79-7 644073 40400
42
Naloxone Approved, Vet_approved Phase 2 465-65-6 5284596
43 Buprenorphine, Naloxone Drug Combination Phase 2
44 Narcotic Antagonists Phase 2
45
Methylprednisolone Approved, Vet_approved 83-43-2 6741
46
Prednisolone Approved, Vet_approved 50-24-8 5755
47
Prednisolone phosphate Approved, Vet_approved 302-25-0
48
Methylprednisolone hemisuccinate Approved 2921-57-5
49
Prednisolone acetate Approved, Vet_approved 52-21-1
50
Prednisolone hemisuccinate Experimental 2920-86-7

Interventional clinical trials:

(show all 11)
# Name Status NCT ID Phase Drugs
1 A Randomized Comparison of Midazolam With Meperidine and Dexmedetomidine Versus Midazolam With Meperidine and Propofol for Sedation During ERCP Completed NCT02475824 Phase 4 Midazolam®;"Meperidine" (pethidine®);Propofol®;Dexmedetomidine (Precedex®)
2 Allogeneic Stem Cell Transplantation in Children and Adolescents With Acute Lymphoblastic Leukaemia Unknown status NCT01423747 Phase 3 VP16;VP16, ATG;Fludarabine, OKT3, Treosulfan, Thiotepa;VP16, ATG
3 Allogeneic Stem Cell Transplantation in Children and Adolescents With Acute Lymphoblastic Leukaemia Unknown status NCT01423500 Phase 3 VP16;VP16, ATG;Fludarabine, OKT3, Treosulfan, Thiotepa;VP16, ATG
4 Allogeneic Stem Cell Transplantation for Children and Adolescents With Acute Lymphoblastic Leukaemia Recruiting NCT01949129 Phase 2, Phase 3 VP16;Thiotepa;Treosulfan;Fludarabine;Busulfan;ATG Thymoglobulin;Cyclophosphamide;Grafalon
5 NIDA-CTN-0100: Optimizing Retention, Duration and Discontinuation Strategies for Opioid Use Disorder Pharmacotherapy (RDD) Not yet recruiting NCT04464980 Phase 2 SL-BUP;XR-BUP;XR-NTX
6 Pilot Study to Identify the Benefits CAREGIVERSPRO-MMD Platform Use Based on the Information and Communications Technology, Dedicated to the Support and Assistance of Dyads Living With Neurocognitive Diseases Including Persons Living With Mild Cognitive Impairment or Mild to Moderate Dementia and Their Primary Caregivers Unknown status NCT03536975
7 Outcomes of Differentiated Models of Care: Multi-Month Dispensing (MMD) and Community ART Refill Groups (CARGs) in Stable ART Patients Unknown status NCT03238846
8 Outcomes of Differentiated Models of Antiretroviral Treatment (ART) Provision: Multi-Month Dispensing (MMD) of ART in Community ART Distribution for Stable HIV Infected Patients Unknown status NCT03438370
9 Therapy Protocol ALL SCT BFM International-open, Multicenter, Controlled, Prospective Study for Therapy and Therapy Optimisation in Patients With Acute Lymphoblastic Leukemia (ALL) and an Indication for Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) Completed NCT00861679
10 Assessment of Medherent Medication Management Device and Adherence Platform Active, not recruiting NCT03775044
11 Implementation and Evaluation of a Community-Based Model for Delivery of Antiretroviral Therapy in Cambodia: A Quasi-Experimental Study Not yet recruiting NCT04766710

Search NIH Clinical Center for Multiple Mitochondrial Dysfunctions Syndrome

Cochrane evidence based reviews: multiple mitochondrial dysfunctions syndrome

Genetic Tests for Multiple Mitochondrial Dysfunctions Syndrome

Genetic tests related to Multiple Mitochondrial Dysfunctions Syndrome:

# Genetic test Affiliating Genes
1 Multiple Mitochondrial Dysfunctions Syndrome 29

Anatomical Context for Multiple Mitochondrial Dysfunctions Syndrome

Publications for Multiple Mitochondrial Dysfunctions Syndrome

Articles related to Multiple Mitochondrial Dysfunctions Syndrome:

(show all 25)
# Title Authors PMID Year
1
Homozygous p.(Glu87Lys) variant in ISCA1 is associated with a multiple mitochondrial dysfunctions syndrome. 61 6
28356563 2017
2
ISCA2 mutation causes infantile neurodegenerative mitochondrial disorder. 6
25539947 2015
3
Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families. 6
25558065 2015
4
Biochemical Impact of a Disease-Causing Ile67Asn Substitution on BOLA3 Protein. 61
33693876 2021
5
Assembly of the [4Fe-4S] cluster of NFU1 requires the coordinated donation of two [2Fe-2S] clusters from the scaffold proteins, ISCU2 and ISCA1. 61
32776106 2020
6
A genetic mimic of cerebral palsy: Homozygous NFU1 mutation with marked intrafamilial phenotypic variation. 61
32747156 2020
7
ISCU interacts with NFU1, and ISCU[4Fe-4S] transfers its Fe-S cluster to NFU1 leading to the production of holo-NFU1. 61
32151725 2020
8
Multiple mitochondrial dysfunctions syndrome 1: An unusual cause of developmental pulmonary hypertension. 61
31970900 2020
9
ISCA1-Related Multiple Mitochondrial Dysfunctions Syndrome 61
31580634 2019
10
Understanding the Mechanism of [4Fe-4S] Cluster Assembly on Eukaryotic Mitochondrial and Cytosolic Aconitase. 61
31436962 2019
11
Reconstitution, characterization, and [2Fe-2S] cluster exchange reactivity of a holo human BOLA3 homodimer. 61
31486956 2019
12
A novel ISCA2 variant responsible for an early-onset neurodegenerative mitochondrial disorder: a case report of multiple mitochondrial dysfunctions syndrome 4. 61
31279336 2019
13
Knockout of ISCA1 causes early embryonic death in rats. 61
31016283 2019
14
Severe Leukoencephalopathy with Clinical Recovery Caused by Recessive BOLA3 Mutations. 61
29654549 2019
15
Multiple Mitochondrial Dysfunctions Syndrome 4 Due to ISCA2 Gene Defects: A Review. 61
31106229 2019
16
Report of the Third Family with Multiple Mitochondrial Dysfunctions Syndrome 5 Caused by the Founder Variant p.(Glu87Lys) in ISCA1. 61
30105122 2018
17
Understanding the molecular basis for multiple mitochondrial dysfunctions syndrome 1 (MMDS1): impact of a disease-causing Gly189Arg substitution on NFU1. 61
28906594 2017
18
A commentary on homozygous p.(Glu87Lys) variant in ISCA1 is associated with a multiple mitochondrial dysfunctions syndrome. 61
28615675 2017
19
A reply to a commentary on homozygous p.(Glu87Lys) variant in ISCA1 is associated with a multiple mitochondrial dysfunctions syndrome. 61
28615676 2017
20
Novel NFU1 Variants Induced MMDS Behaved as Special Leukodystrophy in Chinese Sufferers. 61
28470589 2017
21
Understanding the Molecular Basis of Multiple Mitochondrial Dysfunctions Syndrome 1 (MMDS1)-Impact of a Disease-Causing Gly208Cys Substitution on Structure and Activity of NFU1 in the Fe/S Cluster Biosynthetic Pathway. 61
28161430 2017
22
Mutation of the iron-sulfur cluster assembly gene IBA57 causes fatal infantile leukodystrophy. 61
25971455 2015
23
HIBCH mutations can cause Leigh-like disease with combined deficiency of multiple mitochondrial respiratory chain enzymes and pyruvate dehydrogenase. 61
24299452 2013
24
Homozygous missense mutation in BOLA3 causes multiple mitochondrial dysfunctions syndrome in two siblings. 61
22562699 2013
25
Biogenesis of iron-sulfur clusters in mammalian cells: new insights and relevance to human disease. 61
22382365 2012

Variations for Multiple Mitochondrial Dysfunctions Syndrome

ClinVar genetic disease variations for Multiple Mitochondrial Dysfunctions Syndrome:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ISCA1 NM_030940.4(ISCA1):c.259G>A (p.Glu87Lys) SNV Pathogenic 375415 rs776679653 GRCh37: 9:88881089-88881089
GRCh38: 9:86266174-86266174
2 ISCA2 NM_194279.4(ISCA2):c.229G>A (p.Gly77Ser) SNV Likely pathogenic 183353 rs730882246 GRCh37: 14:74961032-74961032
GRCh38: 14:74494329-74494329
3 NFU1 NM_015700.4(NFU1):c.231-18dup Duplication Uncertain significance 336890 rs372898848 GRCh37: 2:69646748-69646749
GRCh38: 2:69419616-69419617
4 NFU1 NM_001002756.2(NFU1):c.-526CG[1] Microsatellite Uncertain significance 336899 rs777119948 GRCh37: 2:69664700-69664701
GRCh38: 2:69437568-69437569

Expression for Multiple Mitochondrial Dysfunctions Syndrome

Search GEO for disease gene expression data for Multiple Mitochondrial Dysfunctions Syndrome.

Pathways for Multiple Mitochondrial Dysfunctions Syndrome

Pathways related to Multiple Mitochondrial Dysfunctions Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 9.58 ISCU FDX2

GO Terms for Multiple Mitochondrial Dysfunctions Syndrome

Cellular components related to Multiple Mitochondrial Dysfunctions Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.73 PMPCB NUBPL NFU1 LIAS ISCU ISCA2
2 mitochondrial matrix GO:0005759 9.28 PMPCB NUBPL LIAS ISCU ISCA2 ISCA1

Biological processes related to Multiple Mitochondrial Dysfunctions Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 small molecule metabolic process GO:0044281 9.35 ISCU ISCA2 ISCA1 GLRX5 FDX2
2 protein maturation by iron-sulfur cluster transfer GO:0097428 9.33 NFU1 ISCA2 ISCA1
3 protein maturation by [4Fe-4S] cluster transfer GO:0106035 9.26 ISCA2 GLRX5
4 iron-sulfur cluster assembly GO:0016226 9.1 NUBPL NFU1 ISCU ISCA2 ISCA1 IBA57

Molecular functions related to Multiple Mitochondrial Dysfunctions Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 metal ion binding GO:0046872 9.91 PMPCB NUBPL NFU1 LIAS ISCU ISCA2
2 4 iron, 4 sulfur cluster binding GO:0051539 9.55 NUBPL NFU1 LIAS ISCU ISCA2
3 iron ion binding GO:0005506 9.5 NFU1 ISCU ISCA2
4 electron transfer activity GO:0009055 9.37 GLRX5 FDX2
5 2 iron, 2 sulfur cluster binding GO:0051537 9.35 ISCU ISCA2 ISCA1 GLRX5 FDX2
6 iron-sulfur cluster binding GO:0051536 9.23 NUBPL NFU1 LIAS ISCU ISCA2 ISCA1

Sources for Multiple Mitochondrial Dysfunctions Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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