MCID: LKD008
MIFTS: 37

Leukodystrophy, Hypomyelinating, 4

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

Aliases & Classifications for Leukodystrophy, Hypomyelinating, 4

MalaCards integrated aliases for Leukodystrophy, Hypomyelinating, 4:

Name: Leukodystrophy, Hypomyelinating, 4 57 75 29 13 6 73
Mitochondrial Hsp60 Chaperonopathy 57 12 59 75
Mitchap60 Disease 57 12 75
Hld4 57 12 75
Pelizaeus-Merzbacher-Like Disease Due to Hspd1 Mutation 12 59
Hypomyelinating Leukodystrophy 4 12 15
Leukodystrophy, Hypomyelinating, Type 4 40
Mitchap-60 Disease 75

Characteristics:

Orphanet epidemiological data:

59
pelizaeus-merzbacher-like disease due to hspd1 mutation
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal; Age of death: early childhood;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset between birth and 3 months of age
usually fatal in first 2 decades
exacerbation during febrile episodes
allelic disorder to autosomal dominant spg13


HPO:

32
leukodystrophy, hypomyelinating, 4:
Onset and clinical course neonatal onset
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 59  
Rare neurological diseases


Summaries for Leukodystrophy, Hypomyelinating, 4

UniProtKB/Swiss-Prot : 75 Leukodystrophy, hypomyelinating, 4: A severe autosomal recessive hypomyelinating leukodystrophy. Clinically characterized by infantile-onset rotary nystagmus, progressive spastic paraplegia, neurologic regression, motor impairment, profound mental retardation. Death usually occurs within the first two decades of life.

MalaCards based summary : Leukodystrophy, Hypomyelinating, 4, also known as mitochondrial hsp60 chaperonopathy, is related to leukodystrophy and sennetsu fever, and has symptoms including apnea, seizures and shallow breathing. An important gene associated with Leukodystrophy, Hypomyelinating, 4 is HSPD1 (Heat Shock Protein Family D (Hsp60) Member 1), and among its related pathways/superpathways are Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors and Validated targets of C-MYC transcriptional activation. Affiliated tissues include brain, and related phenotypes are nystagmus and seizures

Disease Ontology : 12 A hypomyelinating leukodystrophy characterized by autosomal recessive inheritance of hypotonia, nystagmus, psychomotor developmental delay, and severe hypomyelinating leukoencephalopathy that has material basis in homozygous mutation in the HSPD1 gene on chromosome 2q33.

Description from OMIM: 612233

Related Diseases for Leukodystrophy, Hypomyelinating, 4

Graphical network of the top 20 diseases related to Leukodystrophy, Hypomyelinating, 4:



Diseases related to Leukodystrophy, Hypomyelinating, 4

Symptoms & Phenotypes for Leukodystrophy, Hypomyelinating, 4

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
nystagmus
strabismus

Abdomen Gastrointestinal:
feeding difficulties

Respiratory:
apneic episodes
shallow breathing

Laboratory Abnormalities:
intermittent increase of urinary ethylmalonic acid
serum lactate may be increased during encephalopathic exacerbations

Neurologic Central Nervous System:
seizures
hyperreflexia
choreoathetosis
hypotonia
extensor plantar responses
more
Skeletal:
joint contractures

Head And Neck Head:
microcephaly, acquired


Clinical features from OMIM:

612233

Human phenotypes related to Leukodystrophy, Hypomyelinating, 4:

32 (show all 16)
# Description HPO Frequency HPO Source Accession
1 nystagmus 32 HP:0000639
2 seizures 32 HP:0001250
3 muscular hypotonia 32 HP:0001252
4 hyperreflexia 32 HP:0001347
5 global developmental delay 32 HP:0001263
6 flexion contracture 32 HP:0001371
7 feeding difficulties in infancy 32 HP:0008872
8 strabismus 32 HP:0000486
9 babinski sign 32 HP:0003487
10 apnea 32 HP:0002104
11 intellectual disability, profound 32 HP:0002187
12 choreoathetosis 32 HP:0001266
13 progressive spasticity 32 HP:0002191
14 leukodystrophy 32 HP:0002415
15 postnatal microcephaly 32 HP:0005484
16 generalized hypotonia 32 HP:0001290

UMLS symptoms related to Leukodystrophy, Hypomyelinating, 4:


apnea, seizures, shallow breathing

GenomeRNAi Phenotypes related to Leukodystrophy, Hypomyelinating, 4 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased influenza A H1N1 (A/Hamburg/04/2009) virus numbers GR00195-A-3 9.16 HSPD1 MYC
2 Reduced mammosphere formation GR00396-S 9.02 HSPD1 HSPE1 MYC PLP1 S100A9
3 Decreased influenza A H1N1 (A/WSN/33) virus numbers GR00195-A-2 8.96 HSPD1 MYC

Drugs & Therapeutics for Leukodystrophy, Hypomyelinating, 4

Search Clinical Trials , NIH Clinical Center for Leukodystrophy, Hypomyelinating, 4

Genetic Tests for Leukodystrophy, Hypomyelinating, 4

Genetic tests related to Leukodystrophy, Hypomyelinating, 4:

# Genetic test Affiliating Genes
1 Leukodystrophy, Hypomyelinating, 4 29 HSPD1

Anatomical Context for Leukodystrophy, Hypomyelinating, 4

MalaCards organs/tissues related to Leukodystrophy, Hypomyelinating, 4:

41
Brain

Publications for Leukodystrophy, Hypomyelinating, 4

Articles related to Leukodystrophy, Hypomyelinating, 4:

# Title Authors Year
1
Mitochondrial Hsp60 chaperonopathy causes an autosomal-recessive neurodegenerative disorder linked to brain hypomyelination and leukodystrophy. ( 18571143 )
2008

Variations for Leukodystrophy, Hypomyelinating, 4

UniProtKB/Swiss-Prot genetic disease variations for Leukodystrophy, Hypomyelinating, 4:

75
# Symbol AA change Variation ID SNP ID
1 HSPD1 p.Asp29Gly VAR_054785 rs72466451

ClinVar genetic disease variations for Leukodystrophy, Hypomyelinating, 4:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 HSPD1 NM_199440.1(HSPD1): c.86A> G (p.Asp29Gly) single nucleotide variant Pathogenic rs72466451 GRCh37 Chromosome 2, 198363487: 198363487
2 HSPD1 NM_199440.1(HSPD1): c.86A> G (p.Asp29Gly) single nucleotide variant Pathogenic rs72466451 GRCh38 Chromosome 2, 197498763: 197498763

Expression for Leukodystrophy, Hypomyelinating, 4

Search GEO for disease gene expression data for Leukodystrophy, Hypomyelinating, 4.

Pathways for Leukodystrophy, Hypomyelinating, 4

GO Terms for Leukodystrophy, Hypomyelinating, 4

Biological processes related to Leukodystrophy, Hypomyelinating, 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 positive regulation of gene expression GO:0010628 9.43 GJC2 MYC PLP1
2 protein folding GO:0006457 9.33 HSPD1 HSPE1 HSPE1-MOB4
3 response to unfolded protein GO:0006986 9.32 HSPD1 HSPE1
4 astrocyte development GO:0014002 8.96 PLP1 S100A9
5 activation of cysteine-type endopeptidase activity involved in apoptotic process GO:0006919 8.8 HSPD1 HSPE1 S100A9

Molecular functions related to Leukodystrophy, Hypomyelinating, 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 unfolded protein binding GO:0051082 8.96 HSPD1 HSPE1
2 chaperone binding GO:0051087 8.62 HSPD1 HSPE1

Sources for Leukodystrophy, Hypomyelinating, 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
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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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