MMDS1
MCID: MLT068
MIFTS: 43

Multiple Mitochondrial Dysfunctions Syndrome 1 (MMDS1)

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

Aliases & Classifications for Multiple Mitochondrial Dysfunctions Syndrome 1

MalaCards integrated aliases for Multiple Mitochondrial Dysfunctions Syndrome 1:

Name: Multiple Mitochondrial Dysfunctions Syndrome 1 56 12 73 29 13 6 15 71
Mmds1 56 58 73
Nfu1 Deficiency 12 58
Mmds 56 73
Mitochondrial Dysfunctions Syndrome, Multiple, Type 1 39
Multiple Mitochondrial Dysfunctions Syndrome Type 1 58

Characteristics:

Orphanet epidemiological data:

58
multiple mitochondrial dysfunctions syndrome type 1
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Neonatal;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
onset soon after birth
death by age 15 months


HPO:

31
multiple mitochondrial dysfunctions syndrome 1:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


External Ids:

Disease Ontology 12 DOID:0080133
OMIM 56 605711
OMIM Phenotypic Series 56 PS605711
MeSH 43 D028361
ICD10 via Orphanet 33 E88.8
Orphanet 58 ORPHA401869
UMLS 71 C3276432

Summaries for Multiple Mitochondrial Dysfunctions Syndrome 1

UniProtKB/Swiss-Prot : 73 Multiple mitochondrial dysfunctions syndrome 1: A severe disorder of systemic energy metabolism, resulting in weakness, respiratory failure, lack of neurologic development, lactic acidosis, hyperglycinemia and early death. Some patients show failure to thrive, pulmonary hypertension, hypotonia and irritability. Biochemical features include severe combined deficiency of the 2- oxoacid dehydrogenases, defective lipoic acid synthesis and reduction in activity of mitochondrial respiratory chain complexes.

MalaCards based summary : Multiple Mitochondrial Dysfunctions Syndrome 1, also known as mmds1, is related to multiple mitochondrial dysfunctions syndrome 4 and multiple mitochondrial dysfunctions syndrome 2 with hyperglycinemia, and has symptoms including lethargy and weakness. An important gene associated with Multiple Mitochondrial Dysfunctions Syndrome 1 is NFU1 (NFU1 Iron-Sulfur Cluster Scaffold), and among its related pathways/superpathways are Glyoxylate metabolism and glycine degradation and Mitochondrial iron-sulfur cluster biogenesis. The drugs Erenumab and Salmon calcitonin have been mentioned in the context of this disorder. Affiliated tissues include brain, and related phenotypes are global developmental delay and muscle weakness

Disease Ontology : 12 A multiple mitochondrial dysfunctions syndrome that is characterized by weakness, respiratory failure, lack of neurologic development, lactic acidosis, and early death, and has material basis in autosomal recessive inheritance of homozygous or compound heterozygous mutation in the NFU1 iron-sulfur cluster scaffold gene on chromosome 2p13.

OMIM : 56 Multiple mitochondrial dysfunctions syndrome is a severe autosomal recessive disorder of systemic energy metabolism, resulting in weakness, respiratory failure, lack of neurologic development, lactic acidosis, and early death (summary by Seyda et al., 2001). (605711)

Related Diseases for Multiple Mitochondrial Dysfunctions Syndrome 1

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 1 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 31.4 NFU1 LIAS IBA57 BOLA3
2 multiple mitochondrial dysfunctions syndrome 2 with hyperglycinemia 31.3 NFU1 LIAS IBA57 BOLA3
3 multiple mitochondrial dysfunctions syndrome 3 30.9 NFU1 LIAS IBA57 FDX2 BOLA3
4 multiple mitochondrial dysfunctions syndrome 30.5 NFU1 LIAS ISCU IBA57 HSCB FDX2
5 leukodystrophy 29.6 NFU1 IBA57 FOXRED1
6 lactic acidosis 28.0 NFU1 LIPT2 LIPT1 LIAS ISCU IBA57
7 multiminicore disease 11.9
8 minicore myopathy with external ophthalmoplegia 11.7
9 rigid spine muscular dystrophy 1 11.4
10 miyoshi muscular dystrophy 1 11.2
11 multiple mitochondrial dysfunctions syndrome 5 11.2
12 multiple mitochondrial dysfunctions syndrome 6 11.2
13 central core disease of muscle 10.1
14 myopathy, distal, 1 10.1
15 small cell cancer of the lung 10.1
16 lung cancer 10.1
17 moyamoya disease 1 10.1
18 autosomal recessive disease 10.1
19 mood disorder 10.1
20 myopathy 10.1
21 poliomyelitis 10.1
22 muscular dystrophy 10.1
23 pulmonary hypertension, primary, 1 10.1
24 pyruvate dehydrogenase e1-beta deficiency 10.1
25 pulmonary hypertension 9.9
26 mitochondrial encephalomyopathy 9.9
27 sideroblastic anemia 9.9
28 leigh syndrome with leukodystrophy 9.7 LIPT1 FOXRED1
29 combined oxidative phosphorylation deficiency 19 9.7 ISCU FDX2 BOLA3
30 respiratory failure 9.5 NFU1 IBA57 BOLA3
31 pyruvate dehydrogenase e1-alpha deficiency 9.4 NFU1 LIPT1 IBA57 BOLA3
32 mitochondrial myopathy 9.3 ISCU HSCB FDX2
33 anemia, sideroblastic, and spinocerebellar ataxia 9.2 NFU1 ISCU IBA57 HSCB
34 glycine encephalopathy 8.9 NFU1 LIPT2 LIPT1 LIAS IBA57 BOLA3
35 mitochondrial metabolism disease 8.2 NFU1 LIAS ISCU IBA57 HSCB FOXRED1

Graphical network of the top 20 diseases related to Multiple Mitochondrial Dysfunctions Syndrome 1:



Diseases related to Multiple Mitochondrial Dysfunctions Syndrome 1

Symptoms & Phenotypes for Multiple Mitochondrial Dysfunctions Syndrome 1

Human phenotypes related to Multiple Mitochondrial Dysfunctions Syndrome 1:

31 (show all 11)
# Description HPO Frequency HPO Source Accession
1 global developmental delay 31 HP:0001263
2 muscle weakness 31 HP:0001324
3 failure to thrive 31 HP:0001508
4 feeding difficulties 31 HP:0011968
5 pulmonary arterial hypertension 31 HP:0002092
6 hypertension 31 HP:0000822
7 lethargy 31 HP:0001254
8 respiratory failure 31 HP:0002878
9 lactic acidosis 31 HP:0003128
10 decreased activity of mitochondrial respiratory chain 31 HP:0008972
11 psychomotor retardation 31 HP:0025356

Symptoms via clinical synopsis from OMIM:

56
Growth Other:
failure to thrive

Neurologic Central Nervous System:
lethargy
psychomotor retardation
astrogliosis
decreasing responsiveness
neurologic regression
more
Metabolic Features:
lactic acidosis

Cardiovascular Vascular:
pulmonary hypertension
obstructive vasculopathy

Abdomen Gastrointestinal:
feeding difficulties

Respiratory:
respiratory failure

Muscle Soft Tissue:
weakness

Laboratory Abnormalities:
increased serum and urinary lactate
increased urinary 2-hydroxybutyrate
increased serum glycine, leucine, isoleucine, valine
decreased activity of pyruvate dehydrogenase complex
decreased activity of 2-oxoacid dehydrogenases
more

Clinical features from OMIM:

605711

UMLS symptoms related to Multiple Mitochondrial Dysfunctions Syndrome 1:


lethargy, weakness

Drugs & Therapeutics for Multiple Mitochondrial Dysfunctions Syndrome 1

Drugs for Multiple Mitochondrial Dysfunctions Syndrome 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 10)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Erenumab Approved, Investigational Phase 3 1582205-90-0
2
Salmon calcitonin Approved, Investigational Phase 3 47931-85-1 16129616
3
Calcitonin gene-related peptide Investigational Phase 3 83652-28-2
4 Immunoglobulins Phase 3
5 Immunologic Factors Phase 3
6 Antibodies Phase 3
7 Antibodies, Monoclonal Phase 3
8 Analgesics Phase 3
9 Katacalcin Phase 3
10 calcitonin Phase 3

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Phase 3, Randomized, Double-blind,Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Erenumab in Children (6 to < 12 Years) and Adolescents (12 to < 18 Years) With Episodic Migraine (OASIS PEDIATRIC [EM]) Active, not recruiting NCT03836040 Phase 3 Erenumab Dose 1;Erenumab Dose 2;Erenumab Dose 3
2 A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Erenumab in Children (6 to < 12 Years) and Adolescents (12 to < 18 Years) With Chronic Migraine (OASIS PEDIATRIC [CM]) Active, not recruiting NCT03832998 Phase 3 Erenumab Dose 1;Erenumab Dose 2;Erenumab Dose 3
3 Feeding America's Bravest: Mediterranean Diet-Based Interventions to Change Firefighters' Eating Habits and Improve Cardiovascular Risk Profiles Active, not recruiting NCT02941757

Search NIH Clinical Center for Multiple Mitochondrial Dysfunctions Syndrome 1

Genetic Tests for Multiple Mitochondrial Dysfunctions Syndrome 1

Genetic tests related to Multiple Mitochondrial Dysfunctions Syndrome 1:

# Genetic test Affiliating Genes
1 Multiple Mitochondrial Dysfunctions Syndrome 1 29 NFU1

Anatomical Context for Multiple Mitochondrial Dysfunctions Syndrome 1

MalaCards organs/tissues related to Multiple Mitochondrial Dysfunctions Syndrome 1:

40
Brain

Publications for Multiple Mitochondrial Dysfunctions Syndrome 1

Articles related to Multiple Mitochondrial Dysfunctions Syndrome 1:

(show all 12)
# Title Authors PMID Year
1
A fatal mitochondrial disease is associated with defective NFU1 function in the maturation of a subset of mitochondrial Fe-S proteins. 56 6
22077971 2011
2
Mutations in iron-sulfur cluster scaffold genes NFU1 and BOLA3 cause a fatal deficiency of multiple respiratory chain and 2-oxoacid dehydrogenase enzymes. 56 6
21944046 2011
3
A novel syndrome affecting multiple mitochondrial functions, located by microcell-mediated transfer to chromosome 2p14-2p13. 56 6
11156534 2001
4
Construction and characterization of a highly stable human: rodent monochromosomal hybrid panel for genetic complementation and genome mapping studies. 56
7606932 1995
5
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
6
Multiple mitochondrial dysfunctions syndrome 1: An unusual cause of developmental pulmonary hypertension. 61
31970900 2020
7
ISCA1 mutation in a patient with infantile-onset leukodystrophy causes defects in mitochondrial [4Fe-4S] proteins. 61
29767723 2018
8
Understanding the molecular basis for multiple mitochondrial dysfunctions syndrome 1 (MMDS1): impact of a disease-causing Gly189Arg substitution on NFU1. 61
28906594 2017
9
Analysis of NFU-1 metallocofactor binding-site substitutions-impacts on iron-sulfur cluster coordination and protein structure and function. 61
28906593 2017
10
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
11
Iron-sulfur cluster exchange reactions mediated by the human Nfu protein. 61
27538573 2016
12
Comparative expression analysis of the antagonistic transcription factors EVI1 and MDS1-EVI1 in murine tissues and during in vitro hematopoietic differentiation. 61
9837768 1998

Variations for Multiple Mitochondrial Dysfunctions Syndrome 1

ClinVar genetic disease variations for Multiple Mitochondrial Dysfunctions Syndrome 1:

6 (show all 36) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 NFU1 NFU1, 545G-ASNV Pathogenic 30699
2 NFU1 NM_001002755.4(NFU1):c.622G>T (p.Gly208Cys)SNV Pathogenic 30700 rs374514431 2:69627594-69627594 2:69400462-69400462
3 NFU1 NM_015700.4(NFU1):c.473+5G>ASNV Pathogenic 488563 rs756085990 2:69633149-69633149 2:69406017-69406017
4 NFU1 NM_001002755.4(NFU1):c.544C>T (p.Arg182Trp)SNV Pathogenic 488564 rs1354126704 2:69633155-69633155 2:69406023-69406023
5 NFU1 NC_000002.11:g.(?_69627476)_(69627690_?)dupduplication Likely pathogenic 647954 2:69627476-69627690 2:69400344-69400558
6 NFU1 NM_001002755.4(NFU1):c.485-1G>CSNV Likely pathogenic 804384 2:69633215-69633215 2:69406083-69406083
7 NFU1 NM_001002755.3(NFU1):c.166+8T>ASNV Conflicting interpretations of pathogenicity 336893 rs199927640 2:69659026-69659026 2:69431894-69431894
8 NFU1 NM_001002755.3(NFU1):c.62+10G>ASNV Conflicting interpretations of pathogenicity 336894 rs773351968 2:69664483-69664483 2:69437351-69437351
9 NFU1 NM_001002755.4(NFU1):c.-1G>ASNV Uncertain significance 336895 rs886056267 2:69664555-69664555 2:69437423-69437423
10 NFU1 NM_001002756.2(NFU1):c.-577G>ASNV Uncertain significance 336903 rs531177766 2:69664754-69664754 2:69437622-69437622
11 NFU1 NM_001002755.4(NFU1):c.495A>T (p.Glu165Asp)SNV Uncertain significance 336889 rs886056266 2:69633204-69633204 2:69406072-69406072
12 NFU1 NM_001002755.3(NFU1):c.299C>G (p.Ala100Gly)SNV Uncertain significance 336891 rs139171264 2:69650717-69650717 2:69423585-69423585
13 NFU1 NM_001002755.4(NFU1):c.629G>T (p.Cys210Phe)SNV Uncertain significance 336888 rs201634470 2:69627587-69627587 2:69400455-69400455
14 NFU1 NM_001002756.2(NFU1):c.-425G>ASNV Uncertain significance 336896 rs886056268 2:69664602-69664602 2:69437470-69437470
15 NFU1 NM_001002756.2(NFU1):c.-496G>ASNV Uncertain significance 336898 rs372505661 2:69664673-69664673 2:69437541-69437541
16 NFU1 NM_001002756.2(NFU1):c.-552G>TSNV Uncertain significance 336901 rs764708513 2:69664729-69664729 2:69437597-69437597
17 NFU1 NM_001002756.2(NFU1):c.-443C>TSNV Uncertain significance 336897 rs753424678 2:69664620-69664620 2:69437488-69437488
18 NFU1 NM_001002756.2(NFU1):c.-574T>GSNV Uncertain significance 336902 rs886056269 2:69664751-69664751 2:69437619-69437619
19 NFU1 NM_001002755.4(NFU1):c.*103G>ASNV Uncertain significance 336886 rs774104725 2:69623275-69623275 2:69396143-69396143
20 NFU1 NM_001002755.4(NFU1):c.702G>A (p.Glu234=)SNV Uncertain significance 336887 rs561482249 2:69627514-69627514 2:69400382-69400382
21 NFU1 NM_001002755.3(NFU1):c.167-13T>GSNV Uncertain significance 336892 rs181762580 2:69650862-69650862 2:69423730-69423730
22 NFU1 NM_001002755.4(NFU1):c.332G>T (p.Ser111Ile)SNV Uncertain significance 896543 2:69646707-69646707 2:69419575-69419575
23 NFU1 NM_001002755.4(NFU1):c.84T>A (p.Asn28Lys)SNV Uncertain significance 898173 2:69659116-69659116 2:69431984-69431984
24 NFU1 NM_001002755.4(NFU1):c.12G>A (p.Thr4=)SNV Uncertain significance 898174 2:69664543-69664543 2:69437411-69437411
25 NFU1 NM_001002755.4(NFU1):c.-7G>ASNV Uncertain significance 899272 2:69664561-69664561 2:69437429-69437429
26 NFU1 NM_001002756.2(NFU1):c.-418C>TSNV Uncertain significance 899273 2:69664595-69664595 2:69437463-69437463
27 NFU1 NM_001002756.2(NFU1):c.-511A>GSNV Uncertain significance 899274 2:69664688-69664688 2:69437556-69437556
28 NFU1 NM_001002756.2(NFU1):c.-556C>GSNV Uncertain significance 895184 2:69664733-69664733 2:69437601-69437601
29 NFU1 NM_001002755.3(NFU1):c.545+9T>CSNV Likely benign 539328 rs767405381 2:69633145-69633145 2:69406013-69406013
30 NFU1 NM_001002756.2(NFU1):c.-543T>CSNV Benign 336900 rs73934936 2:69664720-69664720 2:69437588-69437588
31 NFU1 NM_001002755.3(NFU1):c.286C>T (p.Arg96Cys)SNV Benign 138514 rs74637005 2:69650730-69650730 2:69423598-69423598
32 NFU1 NM_001002755.4(NFU1):c.411T>C (p.Ile137=)SNV Benign 138515 rs12474866 2:69642390-69642390 2:69415258-69415258
33 NFU1 NM_001002755.4(NFU1):c.74T>A (p.Met25Lys)SNV Benign 138516 rs4453725 2:69659126-69659126 2:69431994-69431994
34 NFU1 NM_001002755.4(NFU1):c.-6A>GSNV Benign 138517 rs116604978 2:69664560-69664560 2:69437428-69437428
35 NFU1 NM_001002755.3(NFU1):c.62+9C>TSNV Benign 138518 rs114846829 2:69664484-69664484 2:69437352-69437352
36 NFU1 NM_001002755.4(NFU1):c.151G>T (p.Ala51Ser)SNV Benign 214868 rs76646410 2:69659049-69659049 2:69431917-69431917

UniProtKB/Swiss-Prot genetic disease variations for Multiple Mitochondrial Dysfunctions Syndrome 1:

73
# Symbol AA change Variation ID SNP ID
1 NFU1 p.Gly208Cys VAR_066639 rs374514431
2 NFU1 p.Arg21Pro VAR_079757 rs776875884
3 NFU1 p.Arg182Trp VAR_079758 rs135412670
4 NFU1 p.Gly189Arg VAR_079759

Expression for Multiple Mitochondrial Dysfunctions Syndrome 1

Search GEO for disease gene expression data for Multiple Mitochondrial Dysfunctions Syndrome 1.

Pathways for Multiple Mitochondrial Dysfunctions Syndrome 1

Pathways related to Multiple Mitochondrial Dysfunctions Syndrome 1 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
10.68 LIPT2 LIPT1 LIAS
2 10.11 ISCU FDX2
3
Show member pathways
9.64 LIPT2 LIPT1 LIAS

GO Terms for Multiple Mitochondrial Dysfunctions Syndrome 1

Cellular components related to Multiple Mitochondrial Dysfunctions Syndrome 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial matrix GO:0005759 9.43 LIPT2 LIPT1 LIAS ISCU IBA57 FDX2
2 mitochondrion GO:0005739 9.32 NFU1 LIPT2 LIPT1 LIAS ISCU IBA57

Biological processes related to Multiple Mitochondrial Dysfunctions Syndrome 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cellular nitrogen compound metabolic process GO:0034641 9.33 LIPT2 LIPT1 LIAS
2 protein maturation by iron-sulfur cluster transfer GO:0097428 9.32 NFU1 HSCB
3 small molecule metabolic process GO:0044281 9.26 ISCU FDX2
4 protein lipoylation GO:0009249 9.13 LIPT2 LIPT1 LIAS
5 iron-sulfur cluster assembly GO:0016226 8.92 NFU1 ISCU IBA57 HSCB

Molecular functions related to Multiple Mitochondrial Dysfunctions Syndrome 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transferase activity GO:0016740 9.65 RNF170 LIPT2 LIPT1 LIAS IBA57
2 2 iron, 2 sulfur cluster binding GO:0051537 9.16 ISCU FDX2
3 4 iron, 4 sulfur cluster binding GO:0051539 9.13 NFU1 LIAS ISCU
4 iron-sulfur cluster binding GO:0051536 8.92 NFU1 LIAS ISCU FDX2

Sources for Multiple Mitochondrial Dysfunctions Syndrome 1

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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