MCID: MLT119
MIFTS: 25

Multiple Mitochondrial Dysfunctions Syndrome 3

Categories: Genetic diseases, Neuronal diseases, Metabolic diseases, Rare diseases, Eye 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:
onset in utero
two sibs have been reported (last curated july 2013)
death in the perinatal period


HPO:

32
multiple mitochondrial dysfunctions syndrome 3:
Onset and clinical course congenital onset
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 spinal cord, cerebellum and brain, and related phenotypes are high palate and microcephaly

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 9.2 IBA57 IBA57-DT
2 multiple mitochondrial dysfunctions syndrome 9.0 IBA57 IBA57-DT

Symptoms & Phenotypes for Multiple Mitochondrial Dysfunctions Syndrome 3

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Head:
microcephaly

Growth Other:
intrauterine growth retardation

Prenatal Manifestations Amniotic Fluid:
polyhydramnios

Head And Neck Mouth:
high-arched palate

Skeletal:
arthrogryposis

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

Head And Neck Face:
retrognathia

Metabolic Features:
lactic acidosis
metabolic acidosis

Neurologic Central Nervous System:
polymicrogyria
encephalopathy
hypoplasia of the corpus callosum
cerebral atrophy
hypotonia, severe
more
Chest Breasts:
widely spaced nipples

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


Clinical features from OMIM:

615330

Human phenotypes related to Multiple Mitochondrial Dysfunctions Syndrome 3:

32 (show all 15)
# Description HPO Frequency HPO Source Accession
1 high palate 32 HP:0000218
2 microcephaly 32 HP:0000252
3 retrognathia 32 HP:0000278
4 encephalopathy 32 HP:0001298
5 intrauterine growth retardation 32 HP:0001511
6 polyhydramnios 32 HP:0001561
7 metabolic acidosis 32 HP:0001942
8 cerebral atrophy 32 HP:0002059
9 hypoplasia of the corpus callosum 32 HP:0002079
10 polymicrogyria 32 HP:0002126
11 arthrogryposis multiplex congenita 32 HP:0002804
12 lactic acidosis 32 HP:0003128
13 abnormality of mitochondrial metabolism 32 HP:0003287
14 wide intermamillary distance 32 HP:0006610
15 severe muscular hypotonia 32 HP:0006829

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
Spinal Cord, Cerebellum, Brain, 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 24)
# 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 GRCh38 Chromosome 1, 228174812: 228174812
6 IBA57 NM_001010867.3(IBA57): c.462C> T (p.His154=) single nucleotide variant Benign rs148398789 GRCh37 Chromosome 1, 228362513: 228362513
7 IBA57 NM_001010867.3(IBA57): c.167G> A (p.Arg56His) single nucleotide variant no interpretation for the single variant rs1035428169 GRCh38 Chromosome 1, 228165983: 228165983
8 IBA57 NM_001010867.3(IBA57): c.167G> A (p.Arg56His) single nucleotide variant no interpretation for the single variant rs1035428169 GRCh37 Chromosome 1, 228353684: 228353684
9 IBA57 NM_001010867.3(IBA57): c.826C> T (p.Arg276Cys) single nucleotide variant no interpretation for the single variant rs143575106 GRCh37 Chromosome 1, 228362969: 228362969
10 IBA57 NM_001010867.3(IBA57): c.826C> T (p.Arg276Cys) single nucleotide variant no interpretation for the single variant rs143575106 GRCh38 Chromosome 1, 228175268: 228175268
11 IBA57 NM_001010867.3(IBA57): c.801C> T (p.Ala267=) single nucleotide variant Likely benign rs138699407 GRCh37 Chromosome 1, 228362944: 228362944
12 IBA57 NM_001010867.3(IBA57): c.801C> T (p.Ala267=) single nucleotide variant Likely benign rs138699407 GRCh38 Chromosome 1, 228175243: 228175243
13 IBA57 NM_001010867.3(IBA57): c.947A> C (p.Asn316Thr) single nucleotide variant Likely benign rs200319163 GRCh37 Chromosome 1, 228363090: 228363090
14 IBA57 NM_001010867.3(IBA57): c.947A> C (p.Asn316Thr) single nucleotide variant Likely benign rs200319163 GRCh38 Chromosome 1, 228175389: 228175389
15 IBA57 NM_001010867.3(IBA57): c.313C> T (p.Arg105Trp) single nucleotide variant Pathogenic GRCh37 Chromosome 1, 228353830: 228353830
16 IBA57 NM_001010867.3(IBA57): c.313C> T (p.Arg105Trp) single nucleotide variant Pathogenic GRCh38 Chromosome 1, 228166129: 228166129
17 IBA57 NM_001010867.3(IBA57): c.645C> T (p.Asp215=) single nucleotide variant Benign rs61743941 GRCh38 Chromosome 1, 228174995: 228174995
18 IBA57 NM_001010867.3(IBA57): c.645C> T (p.Asp215=) single nucleotide variant Benign rs61743941 GRCh37 Chromosome 1, 228362696: 228362696
19 IBA57 NM_001010867.3(IBA57): c.961C> T (p.Leu321=) single nucleotide variant Likely benign rs376206530 GRCh37 Chromosome 1, 228363104: 228363104
20 IBA57 NM_001010867.3(IBA57): c.961C> T (p.Leu321=) single nucleotide variant Likely benign rs376206530 GRCh38 Chromosome 1, 228175403: 228175403
21 IBA57 NM_001010867.3(IBA57): c.206T> C (p.Phe69Ser) single nucleotide variant Uncertain significance rs778284446 GRCh38 Chromosome 1, 228166022: 228166022
22 IBA57 NM_001010867.3(IBA57): c.206T> C (p.Phe69Ser) single nucleotide variant Uncertain significance rs778284446 GRCh37 Chromosome 1, 228353723: 228353723
23 IBA57 NM_001010867.3(IBA57): c.335T> G (p.Leu112Trp) single nucleotide variant Uncertain significance rs775646159 GRCh38 Chromosome 1, 228166151: 228166151
24 IBA57 NM_001010867.3(IBA57): c.335T> G (p.Leu112Trp) single nucleotide variant Uncertain significance rs775646159 GRCh37 Chromosome 1, 228353852: 228353852

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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