MMDS3
MCID: MLT119
MIFTS: 27

Multiple Mitochondrial Dysfunctions Syndrome 3 (MMDS3)

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

Aliases & Classifications for Multiple Mitochondrial Dysfunctions Syndrome 3

MalaCards integrated aliases for Multiple Mitochondrial Dysfunctions Syndrome 3:

Name: Multiple Mitochondrial Dysfunctions Syndrome 3 57 12 75 29 6 73
Mmds3 57 75
Mitochondrial Dysfunctions, Multiple, Syndrome, Type 3 40
Multiple Mitochondrial Dysfunctions Syndrome Type 3 59
Iba57 Deficiency 59

Characteristics:

Orphanet epidemiological data:

59
multiple mitochondrial dysfunctions syndrome type 3
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
highly variable severity
onset in utero
some patients may have normal early development and then show regression in the first months of life
death may occur in infancy or early childhood


HPO:

32
multiple mitochondrial dysfunctions syndrome 3:
Onset and clinical course variable expressivity congenital onset progressive
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Multiple Mitochondrial Dysfunctions Syndrome 3

OMIM : 57 MMDS3 is an autosomal recessive severe neurodegenerative disorder characterized by loss of previously acquired developmental milestones in the first months or years of life. Some affected patients have normal development in early infancy before the onset of symptoms, whereas others show delays from birth. Features included loss of motor function, spasticity, pyramidal signs, loss of speech, and cognitive impairment. The disease course is highly variable: some patients die of respiratory failure early in childhood, whereas some survive but may be bedridden with a feeding tube. Less commonly, some patients may survive and have a stable course with motor deficits and mild or even absent cognitive impairment, although there may be fluctuating symptoms, often in response to infection. Other variable features include visual problems and seizures. Brain imaging shows diffuse leukodystrophy in the subcortical region, brainstem, cerebellum, and spinal cord. Laboratory studies tend to show increased lactate and CSF glycine, and decreased activity of mitochondrial complexes I and II, although these findings are also variable. There may be additional biochemical evidence of mitochondrial dysfunction (summary by Liu et al., 2018). For a general description and a discussion of genetic heterogeneity of multiple mitochondrial dysfunctions syndrome, see MMDS1 (605711). (615330)

MalaCards based summary : Multiple Mitochondrial Dysfunctions Syndrome 3, also known as mmds3, is related to spastic paraplegia 74, autosomal recessive and multiple mitochondrial dysfunctions syndrome. An important gene associated with Multiple Mitochondrial Dysfunctions Syndrome 3 is IBA57 (IBA57, Iron-Sulfur Cluster Assembly). Affiliated tissues include brain, spinal cord and cerebellum, and related phenotypes are high palate and nystagmus

UniProtKB/Swiss-Prot : 75 Multiple mitochondrial dysfunctions syndrome 3: 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.

Related Diseases for Multiple Mitochondrial Dysfunctions Syndrome 3

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 Multiple Mitochondrial Dysfunctions Syndrome 2

Diseases related to Multiple Mitochondrial Dysfunctions Syndrome 3 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 spastic paraplegia 74, autosomal recessive 9.8 IBA57 IBA57-DT
2 multiple mitochondrial dysfunctions syndrome 9.7 IBA57 IBA57-DT

Symptoms & Phenotypes for Multiple Mitochondrial Dysfunctions Syndrome 3

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
nystagmus
visual impairment
optic atrophy
loss of visual fixation

Neurologic Central Nervous System:
developmental regression
spastic tetraplegia
irritability
encephalopathy
hypoplasia of the corpus callosum
more
Head And Neck Face:
retrognathia

Prenatal Manifestations Amniotic Fluid:
polyhydramnios

Chest Breasts:
widely spaced nipples

Growth Other:
intrauterine growth retardation (iugr)

Laboratory Abnormalities:
increased serum and csf lactate
increased serum and csf glycine

Respiratory:
respiratory insufficiency
respiratory failure

Head And Neck Head:
microcephaly

Metabolic Features:
lactic acidosis
metabolic acidosis
regression may accompany episodic fever

Head And Neck Mouth:
high-arched palate

Abdomen Gastrointestinal:
poor feeding

Muscle Soft Tissue:
hypotonia, severe
defects in mitochondria respiratory activities, mainly complexes i, ii, and iv
defects in lipoate-containing mitochondrial enzyme complexes

Skeletal:
arthrogryposis (uncommon)


Clinical features from OMIM:

615330

Human phenotypes related to Multiple Mitochondrial Dysfunctions Syndrome 3:

32 (show all 27)
# Description HPO Frequency HPO Source Accession
1 high palate 32 HP:0000218
2 nystagmus 32 HP:0000639
3 seizures 32 very rare (1%) HP:0001250
4 developmental regression 32 HP:0002376
5 microcephaly 32 HP:0000252
6 visual impairment 32 HP:0000505
7 optic atrophy 32 HP:0000648
8 cognitive impairment 32 HP:0100543
9 spastic tetraplegia 32 HP:0002510
10 edema 32 HP:0000969
11 irritability 32 HP:0000737
12 retrognathia 32 HP:0000278
13 intrauterine growth retardation 32 HP:0001511
14 wide intermamillary distance 32 HP:0006610
15 arthrogryposis multiplex congenita 32 HP:0002804
16 lactic acidosis 32 HP:0003128
17 abnormality of mitochondrial metabolism 32 HP:0003287
18 respiratory failure 32 HP:0002878
19 polyhydramnios 32 HP:0001561
20 metabolic acidosis 32 HP:0001942
21 polymicrogyria 32 HP:0002126
22 severe muscular hypotonia 32 HP:0006829
23 encephalopathy 32 HP:0001298
24 hypoplasia of the corpus callosum 32 HP:0002079
25 cerebral atrophy 32 HP:0002059
26 leukodystrophy 32 HP:0002415
27 episodic fever 32 HP:0001954

Drugs & Therapeutics for Multiple Mitochondrial Dysfunctions Syndrome 3

Search Clinical Trials , NIH Clinical Center for Multiple Mitochondrial Dysfunctions Syndrome 3

Genetic Tests for Multiple Mitochondrial Dysfunctions Syndrome 3

Genetic tests related to Multiple Mitochondrial Dysfunctions Syndrome 3:

# Genetic test Affiliating Genes
1 Multiple Mitochondrial Dysfunctions Syndrome 3 29 IBA57

Anatomical Context for Multiple Mitochondrial Dysfunctions Syndrome 3

MalaCards organs/tissues related to Multiple Mitochondrial Dysfunctions Syndrome 3:

41
Brain, Spinal Cord, Cerebellum, Eye, Medulla Oblongata

Publications for Multiple Mitochondrial Dysfunctions Syndrome 3

Variations for Multiple Mitochondrial Dysfunctions Syndrome 3

UniProtKB/Swiss-Prot genetic disease variations for Multiple Mitochondrial Dysfunctions Syndrome 3:

75
# Symbol AA change Variation ID SNP ID
1 IBA57 p.Gln314Pro VAR_069821 rs587777016

ClinVar genetic disease variations for Multiple Mitochondrial Dysfunctions Syndrome 3:

6 (show all 46)
# Gene Variation Type Significance SNP ID Assembly Location
1 IBA57 NM_001010867.3(IBA57): c.941A> C (p.Gln314Pro) single nucleotide variant Pathogenic rs587777016 GRCh37 Chromosome 1, 228363084: 228363084
2 IBA57 NM_001010867.3(IBA57): c.941A> C (p.Gln314Pro) single nucleotide variant Pathogenic rs587777016 GRCh38 Chromosome 1, 228175383: 228175383
3 IBA57 NM_001010867.3(IBA57): c.264C> G (p.Ala88=) single nucleotide variant Benign/Likely benign rs13375853 GRCh37 Chromosome 1, 228353781: 228353781
4 IBA57 NM_001010867.3(IBA57): c.264C> G (p.Ala88=) single nucleotide variant Benign/Likely benign rs13375853 GRCh38 Chromosome 1, 228166080: 228166080
5 IBA57 NM_001010867.3(IBA57): c.462C> T (p.His154=) single nucleotide variant Benign rs148398789 GRCh37 Chromosome 1, 228362513: 228362513
6 IBA57 NM_001010867.3(IBA57): c.462C> T (p.His154=) single nucleotide variant Benign rs148398789 GRCh38 Chromosome 1, 228174812: 228174812
7 IBA57 NM_001010867.3(IBA57): c.801C> T (p.Ala267=) single nucleotide variant Likely benign rs138699407 GRCh37 Chromosome 1, 228362944: 228362944
8 IBA57 NM_001010867.3(IBA57): c.801C> T (p.Ala267=) single nucleotide variant Likely benign rs138699407 GRCh38 Chromosome 1, 228175243: 228175243
9 IBA57 NM_001010867.3(IBA57): c.947A> C (p.Asn316Thr) single nucleotide variant Likely benign rs200319163 GRCh37 Chromosome 1, 228363090: 228363090
10 IBA57 NM_001010867.3(IBA57): c.947A> C (p.Asn316Thr) single nucleotide variant Likely benign rs200319163 GRCh38 Chromosome 1, 228175389: 228175389
11 IBA57 NM_001010867.3(IBA57): c.313C> T (p.Arg105Trp) single nucleotide variant Pathogenic GRCh37 Chromosome 1, 228353830: 228353830
12 IBA57 NM_001010867.3(IBA57): c.313C> T (p.Arg105Trp) single nucleotide variant Pathogenic GRCh38 Chromosome 1, 228166129: 228166129
13 IBA57 NM_001010867.3(IBA57): c.645C> T (p.Asp215=) single nucleotide variant Benign rs61743941 GRCh38 Chromosome 1, 228174995: 228174995
14 IBA57 NM_001010867.3(IBA57): c.645C> T (p.Asp215=) single nucleotide variant Benign rs61743941 GRCh37 Chromosome 1, 228362696: 228362696
15 IBA57 NM_001010867.3(IBA57): c.961C> T (p.Leu321=) single nucleotide variant Likely benign rs376206530 GRCh38 Chromosome 1, 228175403: 228175403
16 IBA57 NM_001010867.3(IBA57): c.961C> T (p.Leu321=) single nucleotide variant Likely benign rs376206530 GRCh37 Chromosome 1, 228363104: 228363104
17 IBA57 NM_001010867.3(IBA57): c.206T> C (p.Phe69Ser) single nucleotide variant Uncertain significance rs778284446 GRCh38 Chromosome 1, 228166022: 228166022
18 IBA57 NM_001010867.3(IBA57): c.206T> C (p.Phe69Ser) single nucleotide variant Uncertain significance rs778284446 GRCh37 Chromosome 1, 228353723: 228353723
19 IBA57 NM_001010867.3(IBA57): c.335T> G (p.Leu112Trp) single nucleotide variant Uncertain significance rs775646159 GRCh38 Chromosome 1, 228166151: 228166151
20 IBA57 NM_001010867.3(IBA57): c.335T> G (p.Leu112Trp) single nucleotide variant Uncertain significance rs775646159 GRCh37 Chromosome 1, 228353852: 228353852
21 IBA57 NM_001010867.3(IBA57): c.436C> T (p.Arg146Trp) single nucleotide variant Pathogenic/Likely pathogenic rs73095427 GRCh37 Chromosome 1, 228362487: 228362487
22 IBA57 NM_001010867.3(IBA57): c.436C> T (p.Arg146Trp) single nucleotide variant Pathogenic/Likely pathogenic rs73095427 GRCh38 Chromosome 1, 228174786: 228174786
23 IBA57 NM_001010867.3(IBA57): c.586T> G (p.Trp196Gly) single nucleotide variant Pathogenic GRCh37 Chromosome 1, 228362637: 228362637
24 IBA57 NM_001010867.3(IBA57): c.586T> G (p.Trp196Gly) single nucleotide variant Pathogenic GRCh38 Chromosome 1, 228174936: 228174936
25 IBA57 NM_001010867.3(IBA57): c.686C> T (p.Pro229Leu) single nucleotide variant Pathogenic GRCh37 Chromosome 1, 228362829: 228362829
26 IBA57 NM_001010867.3(IBA57): c.686C> T (p.Pro229Leu) single nucleotide variant Pathogenic GRCh38 Chromosome 1, 228175128: 228175128
27 IBA57 NM_001010867.3(IBA57): c.706C> T (p.Pro236Ser) single nucleotide variant Pathogenic rs769063859 GRCh37 Chromosome 1, 228362849: 228362849
28 IBA57 NM_001010867.3(IBA57): c.706C> T (p.Pro236Ser) single nucleotide variant Pathogenic rs769063859 GRCh38 Chromosome 1, 228175148: 228175148
29 IBA57 NM_001010867.3(IBA57): c.286T> C (p.Tyr96His) single nucleotide variant Pathogenic rs765926471 GRCh37 Chromosome 1, 228353803: 228353803
30 IBA57 NM_001010867.3(IBA57): c.286T> C (p.Tyr96His) single nucleotide variant Pathogenic rs765926471 GRCh38 Chromosome 1, 228166102: 228166102
31 IBA57 NM_001010867.3(IBA57): c.316A> G (p.Thr106Ala) single nucleotide variant Pathogenic rs1053773776 GRCh37 Chromosome 1, 228353833: 228353833
32 IBA57 NM_001010867.3(IBA57): c.316A> G (p.Thr106Ala) single nucleotide variant Pathogenic rs1053773776 GRCh38 Chromosome 1, 228166132: 228166132
33 IBA57 NM_001010867.3(IBA57): c.697C> T (p.Arg233Ter) single nucleotide variant Pathogenic GRCh37 Chromosome 1, 228362840: 228362840
34 IBA57 NM_001010867.3(IBA57): c.697C> T (p.Arg233Ter) single nucleotide variant Pathogenic GRCh38 Chromosome 1, 228175139: 228175139
35 IBA57 NM_001010867.3(IBA57): c.323A> C (p.Tyr108Ser) single nucleotide variant Pathogenic rs781627051 GRCh37 Chromosome 1, 228353840: 228353840
36 IBA57 NM_001010867.3(IBA57): c.323A> C (p.Tyr108Ser) single nucleotide variant Pathogenic rs781627051 GRCh38 Chromosome 1, 228166139: 228166139
37 IBA57 NM_001010867.3(IBA57): c.940C> T (p.Gln314Ter) single nucleotide variant Pathogenic GRCh37 Chromosome 1, 228363083: 228363083
38 IBA57 NM_001010867.3(IBA57): c.940C> T (p.Gln314Ter) single nucleotide variant Pathogenic GRCh38 Chromosome 1, 228175382: 228175382
39 IBA57 NM_001010867.3(IBA57): c.150C> A (p.Cys50Ter) single nucleotide variant Pathogenic rs765132163 GRCh37 Chromosome 1, 228353667: 228353667
40 IBA57 NM_001010867.3(IBA57): c.150C> A (p.Cys50Ter) single nucleotide variant Pathogenic rs765132163 GRCh38 Chromosome 1, 228165966: 228165966
41 IBA57 NM_001010867.3(IBA57): c.354C> A (p.His118Gln) single nucleotide variant Uncertain significance GRCh38 Chromosome 1, 228174704: 228174704
42 IBA57 NM_001010867.3(IBA57): c.354C> A (p.His118Gln) single nucleotide variant Uncertain significance GRCh37 Chromosome 1, 228362405: 228362405
43 IBA57 NM_001010867.3(IBA57): c.1033G> A (p.Ala345Thr) single nucleotide variant Uncertain significance rs150912462 GRCh37 Chromosome 1, 228363176: 228363176
44 IBA57 NM_001010867.3(IBA57): c.1033G> A (p.Ala345Thr) single nucleotide variant Uncertain significance rs150912462 GRCh38 Chromosome 1, 228175475: 228175475
45 IBA57 NM_001010867.3(IBA57): c.215G> C (p.Gly72Ala) single nucleotide variant Uncertain significance GRCh37 Chromosome 1, 228353732: 228353732
46 IBA57 NM_001010867.3(IBA57): c.215G> C (p.Gly72Ala) single nucleotide variant Uncertain significance GRCh38 Chromosome 1, 228166031: 228166031

Expression for Multiple Mitochondrial Dysfunctions Syndrome 3

Search GEO for disease gene expression data for Multiple Mitochondrial Dysfunctions Syndrome 3.

Pathways for Multiple Mitochondrial Dysfunctions Syndrome 3

GO Terms for Multiple Mitochondrial Dysfunctions Syndrome 3

Sources for Multiple Mitochondrial Dysfunctions Syndrome 3

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