MMDS1
MCID: MLT068
MIFTS: 42

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
Nfu1 Deficiency 12 58
Mmds1 56 73
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 nfu1 deficiency, is related to multiple mitochondrial dysfunctions syndrome 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 is Mitochondrial iron-sulfur cluster biogenesis. The drugs Salmon Calcitonin and Erenumab have been mentioned in the context of this disorder. Affiliated tissues include brain, lung and eye, and related phenotypes are failure to thrive and hypertension

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 37)
# Related Disease Score Top Affiliating Genes
1 multiple mitochondrial dysfunctions syndrome 32.1 NFU1 ISCA2 IBA57 BOLA3
2 multiple mitochondrial dysfunctions syndrome 2 with hyperglycinemia 30.7 NFU1 LIAS ISCA2 IBA57 BOLA3
3 multiple mitochondrial dysfunctions syndrome 4 30.1 NFU1 LIAS ISCA2 IBA57 GLRX5 BOLA3
4 multiple mitochondrial dysfunctions syndrome 3 29.5 NFU1 LIAS ISCA2 IBA57 GLRX5 FDX2
5 leukodystrophy 29.0 NFU1 ISCA2 IBA57 GLRX5
6 lactic acidosis 28.1 NFU1 LIAS ISCU ISCA2 IBA57 BOLA3
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 autosomal recessive disease 10.1
18 mood disorder 10.1
19 myopathy 10.1
20 poliomyelitis 10.1
21 muscular dystrophy 10.1
22 malignant hyperthermia susceptibility 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 pyruvate dehydrogenase e1-alpha deficiency 9.9 NFU1 IBA57 BOLA3
29 hypochromic microcytic anemia 9.5 ISCA2 IBA57 GLRX5
30 respiratory failure 9.4 NFU1 ISCA2 IBA57 BOLA3
31 autosomal recessive cerebellar ataxia 9.3 ISCU HSCB
32 mitochondrial myopathy 9.2 ISCU HSCB FDX2
33 aceruloplasminemia 9.1 ISCU IBA57 GLRX5
34 anemia, sideroblastic, 1 8.9 ISCU ISCA2 IBA57 GLRX5
35 glycine encephalopathy 8.8 NFU1 LIAS ISCA2 IBA57 GLRX5 BOLA3
36 anemia, sideroblastic, and spinocerebellar ataxia 8.4 NFU1 ISCU ISCA2 IBA57 HSCB GLRX5
37 mitochondrial metabolism disease 8.4 NFU1 LIAS ISCU ISCA2 GLRX5 BOLA3

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 failure to thrive 31 HP:0001508
2 hypertension 31 HP:0000822
3 muscle weakness 31 HP:0001324
4 global developmental delay 31 HP:0001263
5 feeding difficulties 31 HP:0011968
6 pulmonary arterial hypertension 31 HP:0002092
7 lactic acidosis 31 HP:0003128
8 respiratory failure 31 HP:0002878
9 lethargy 31 HP:0001254
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

Metabolic Features:
lactic acidosis

Neurologic Central Nervous System:
lethargy
psychomotor retardation
astrogliosis
decreasing responsiveness
neurologic regression
more
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
Salmon Calcitonin Approved, Investigational Phase 3 47931-85-1 16129616
2 Erenumab Approved, Investigational Phase 3 1582205-90-0
3
Calcitonin gene-related peptide Investigational Phase 3 83652-28-2
4 Immunologic Factors Phase 3
5 Antibodies, Monoclonal Phase 3
6 Analgesics Phase 3
7 Katacalcin Phase 3
8 Antibodies Phase 3
9 calcitonin Phase 3
10 Immunoglobulins 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]) 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]) 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, Lung, Eye

Publications for Multiple Mitochondrial Dysfunctions Syndrome 1

Articles related to Multiple Mitochondrial Dysfunctions Syndrome 1:

(show all 11)
# 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
Multiple mitochondrial dysfunctions syndrome 1: An unusual cause of developmental pulmonary hypertension. 61
31970900 2020
6
ISCA1 mutation in a patient with infantile-onset leukodystrophy causes defects in mitochondrial [4Fe-4S] proteins. 61
29767723 2018
7
Analysis of NFU-1 metallocofactor binding-site substitutions-impacts on iron-sulfur cluster coordination and protein structure and function. 61
28906593 2017
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
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
10
Iron-sulfur cluster exchange reactions mediated by the human Nfu protein. 61
27538573 2016
11
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 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 NFU1 NFU1, 545G-ASNV Pathogenic 30699
2 NFU1 NM_001002755.3(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_015700.4(NFU1):c.472C>T (p.Arg158Trp)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.629G>T (p.Cys210Phe)SNV Uncertain significance 336888 rs201634470 2:69627587-69627587 2:69400455-69400455
8 NFU1 NM_001002755.3(NFU1):c.545+9T>CSNV Likely benign 539328 rs767405381 2:69633145-69633145 2:69406013-69406013
9 NFU1 NM_001002755.3(NFU1):c.411T>C (p.Ile137=)SNV Benign/Likely benign 138515 rs12474866 2:69642390-69642390 2:69415258-69415258

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 9.58 ISCU FDX2

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 LIAS ISCU ISCA2 IBA57 GLRX5 FDX2
2 mitochondrion GO:0005739 9.28 NFU1 LIAS ISCU ISCA2 IBA57 HSCB

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

# Name GO ID Score Top Affiliating Genes
1 protein maturation by iron-sulfur cluster transfer GO:0097428 9.33 NFU1 ISCA2 HSCB
2 electron transport chain GO:0022900 9.32 GLRX5 FDX2
3 protein lipoylation GO:0009249 9.26 LIAS GLRX5
4 small molecule metabolic process GO:0044281 9.26 ISCU ISCA2 GLRX5 FDX2
5 iron-sulfur cluster assembly GO:0016226 9.02 NFU1 ISCU ISCA2 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 metal ion binding GO:0046872 9.86 RNF170 NFU1 LIAS ISCU ISCA2 HSCB
2 iron ion binding GO:0005506 9.5 NFU1 ISCU ISCA2
3 4 iron, 4 sulfur cluster binding GO:0051539 9.46 NFU1 LIAS ISCU ISCA2
4 electron transfer activity GO:0009055 9.37 GLRX5 FDX2
5 2 iron, 2 sulfur cluster binding GO:0051537 9.26 ISCU ISCA2 GLRX5 FDX2
6 iron-sulfur cluster binding GO:0051536 9.1 NFU1 LIAS ISCU ISCA2 GLRX5 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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