MCID: MLT139
MIFTS: 24

Multiple Mitochondrial Dysfunctions Syndrome 4

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

Aliases & Classifications for Multiple Mitochondrial Dysfunctions Syndrome 4

MalaCards integrated aliases for Multiple Mitochondrial Dysfunctions Syndrome 4:

Name: Multiple Mitochondrial Dysfunctions Syndrome 4 57 12 75 29 6
Mmds4 57 75
Mitochondrial Dysfunctions, Multiple, Syndrome, Type 4 40
Multiple Mitochondrial Dysfunctions Syndrome Type 4 59

Characteristics:

Orphanet epidemiological data:

59
multiple mitochondrial dysfunctions syndrome type 4
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy; Age of death: early childhood,infantile;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
death in early childhood may occur
onset in the first year of life


HPO:

32
multiple mitochondrial dysfunctions syndrome 4:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 57 616370
Disease Ontology 12 DOID:0080136
Orphanet 59 ORPHA457406
MeSH 44 D028361

Summaries for Multiple Mitochondrial Dysfunctions Syndrome 4

OMIM : 57 MMDS4 is an autosomal recessive neurodegenerative disorder that usually results in death in early childhood. Affected individuals have normal development for the first months of life, but thereafter show progressive loss of motor and social skills with hypotonia, spasticity, and nystagmus. Patients regress to a vegetative state with lack of eye contact and speech, and poor feeding. Most patients have optic atrophy, and some may develop seizures. Brain imaging shows diffuse leukodystrophy in the subcortical region, brainstem, cerebellum, and spinal cord. Laboratory studies tend to show increased CSF glycine and decreased activity of mitochondrial complex II; there may be additional biochemical evidence of mitochondrial dysfunction (summary by Alaimo et al., 2018). For a general description and a discussion of genetic heterogeneity of multiple mitochondrial dysfunctions syndrome, see MMDS1 (605711). (616370)

MalaCards based summary : Multiple Mitochondrial Dysfunctions Syndrome 4, also known as mmds4, is related to isca2-related mitochondrial disorder and niemann-pick disease, type c2. An important gene associated with Multiple Mitochondrial Dysfunctions Syndrome 4 is ISCA2 (Iron-Sulfur Cluster Assembly 2). Affiliated tissues include eye, cerebellum and spinal cord, and related phenotypes are optic atrophy and spasticity

UniProtKB/Swiss-Prot : 75 Multiple mitochondrial dysfunctions syndrome 4: A severe disorder of systemic energy metabolism, resulting in weakness, respiratory failure, lack of neurologic development, lactic acidosis, hyperglycinemia and early death.

Related Diseases for Multiple Mitochondrial Dysfunctions Syndrome 4

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 4 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 isca2-related mitochondrial disorder 11.2
2 niemann-pick disease, type c2 9.3 ISCA2 NPC2
3 multiple mitochondrial dysfunctions syndrome 9.2 ISCA2 NPC2
4 niemann-pick disease 9.0 ISCA2 NPC2

Symptoms & Phenotypes for Multiple Mitochondrial Dysfunctions Syndrome 4

Symptoms via clinical synopsis from OMIM:

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

Muscle Soft Tissue:
hypotonia
atrophic fibers seen on biopsy
some abnormal aggregation of mitochondria

Neurologic Central Nervous System:
spasticity
hyperreflexia
absent speech
periventricular white matter abnormalities
neurodevelopmental regression to a vegetative state
more
Laboratory Abnormalities:
increased csf glycine, glutamate, and lactate
fibroblasts show decreased mitochondrial complex ii activity
mildly decreased complex iv activity
decreased mtdna levels
decreased mitochondrial membrane potential
more

Clinical features from OMIM:

616370

Human phenotypes related to Multiple Mitochondrial Dysfunctions Syndrome 4:

32
# Description HPO Frequency HPO Source Accession
1 optic atrophy 32 HP:0000648
2 spasticity 32 HP:0001257
3 absent speech 32 HP:0001344
4 leukodystrophy 32 HP:0002415
5 abnormality of the periventricular white matter 32 HP:0002518

Drugs & Therapeutics for Multiple Mitochondrial Dysfunctions Syndrome 4

Search Clinical Trials , NIH Clinical Center for Multiple Mitochondrial Dysfunctions Syndrome 4

Genetic Tests for Multiple Mitochondrial Dysfunctions Syndrome 4

Genetic tests related to Multiple Mitochondrial Dysfunctions Syndrome 4:

# Genetic test Affiliating Genes
1 Multiple Mitochondrial Dysfunctions Syndrome 4 29 ISCA2

Anatomical Context for Multiple Mitochondrial Dysfunctions Syndrome 4

MalaCards organs/tissues related to Multiple Mitochondrial Dysfunctions Syndrome 4:

41
Eye, Cerebellum, Spinal Cord, Brain

Publications for Multiple Mitochondrial Dysfunctions Syndrome 4

Variations for Multiple Mitochondrial Dysfunctions Syndrome 4

UniProtKB/Swiss-Prot genetic disease variations for Multiple Mitochondrial Dysfunctions Syndrome 4:

75
# Symbol AA change Variation ID SNP ID
1 ISCA2 p.Gly77Ser VAR_073794 rs730882246

ClinVar genetic disease variations for Multiple Mitochondrial Dysfunctions Syndrome 4:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 ISCA2 NM_194279.3(ISCA2): c.229G> A (p.Gly77Ser) single nucleotide variant Pathogenic/Likely pathogenic rs730882246 GRCh38 Chromosome 14, 74494329: 74494329
2 ISCA2 NM_194279.3(ISCA2): c.229G> A (p.Gly77Ser) single nucleotide variant Pathogenic/Likely pathogenic rs730882246 GRCh37 Chromosome 14, 74961032: 74961032
3 ISCA2 NM_194279.3(ISCA2): c.295delT (p.Phe99Leufs) deletion Pathogenic GRCh38 Chromosome 14, 74494830: 74494830
4 ISCA2 NM_194279.3(ISCA2): c.295delT (p.Phe99Leufs) deletion Pathogenic GRCh37 Chromosome 14, 74961533: 74961533
5 ISCA2 NM_194279.3(ISCA2): c.334A> G (p.Ser112Gly) single nucleotide variant Pathogenic rs767352340 GRCh38 Chromosome 14, 74494869: 74494869
6 ISCA2 NM_194279.3(ISCA2): c.334A> G (p.Ser112Gly) single nucleotide variant Pathogenic rs767352340 GRCh37 Chromosome 14, 74961572: 74961572

Expression for Multiple Mitochondrial Dysfunctions Syndrome 4

Search GEO for disease gene expression data for Multiple Mitochondrial Dysfunctions Syndrome 4.

Pathways for Multiple Mitochondrial Dysfunctions Syndrome 4

GO Terms for Multiple Mitochondrial Dysfunctions Syndrome 4

Sources for Multiple Mitochondrial Dysfunctions Syndrome 4

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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