HLD4
MCID: LKD008
MIFTS: 36

Leukodystrophy, Hypomyelinating, 4 (HLD4)

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

Aliases & Classifications for Leukodystrophy, Hypomyelinating, 4

MalaCards integrated aliases for Leukodystrophy, Hypomyelinating, 4:

Name: Leukodystrophy, Hypomyelinating, 4 58 76 30 13 6 74
Mitochondrial Hsp60 Chaperonopathy 58 12 60 76
Mitchap60 Disease 58 12 76
Hld4 58 12 76
Pelizaeus-Merzbacher-Like Disease Due to Hspd1 Mutation 12 60
Hypomyelinating Leukodystrophy 4 12 15
Leukodystrophy, Hypomyelinating, Type 4 41
Mitchap-60 Disease 76

Characteristics:

Orphanet epidemiological data:

60
pelizaeus-merzbacher-like disease due to hspd1 mutation
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal; Age of death: early childhood;

OMIM:

58
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:

33
leukodystrophy, hypomyelinating, 4:
Onset and clinical course neonatal onset
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 60  
Rare neurological diseases


Summaries for Leukodystrophy, Hypomyelinating, 4

UniProtKB/Swiss-Prot : 76 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 seizures, apnea 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

Human phenotypes related to Leukodystrophy, Hypomyelinating, 4:

33 (show all 16)
# Description HPO Frequency HPO Source Accession
1 nystagmus 33 HP:0000639
2 seizures 33 HP:0001250
3 muscular hypotonia 33 HP:0001252
4 hyperreflexia 33 HP:0001347
5 global developmental delay 33 HP:0001263
6 flexion contracture 33 HP:0001371
7 feeding difficulties in infancy 33 HP:0008872
8 strabismus 33 HP:0000486
9 babinski sign 33 HP:0003487
10 apnea 33 HP:0002104
11 intellectual disability, profound 33 HP:0002187
12 choreoathetosis 33 HP:0001266
13 progressive spasticity 33 HP:0002191
14 generalized hypotonia 33 HP:0001290
15 leukodystrophy 33 HP:0002415
16 postnatal microcephaly 33 HP:0005484

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Eyes:
nystagmus
strabismus

Abdomen Gastrointestinal:
feeding difficulties

Respiratory:
shallow breathing
apneic episodes

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

UMLS symptoms related to Leukodystrophy, Hypomyelinating, 4:


seizures, apnea, shallow breathing

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

27
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Reduced mammosphere formation GR00396-S 9.02 HSPD1 HSPE1 MYC PLP1 S100A9

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 30 HSPD1

Anatomical Context for Leukodystrophy, Hypomyelinating, 4

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

42
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:

76
# 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
3 POLR3A NM_007055.4(POLR3A): c.2471A> C (p.His824Pro) single nucleotide variant Likely pathogenic GRCh38 Chromosome 10, 78000983: 78000983
4 POLR3A NM_007055.4(POLR3A): c.2471A> C (p.His824Pro) single nucleotide variant Likely pathogenic GRCh37 Chromosome 10, 79760741: 79760741

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

Cellular components related to Leukodystrophy, Hypomyelinating, 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 rough endoplasmic reticulum GO:0005791 8.65 MYC
2 myelin sheath GO:0043209 8.62 GJC2 PLP1

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 response to unfolded protein GO:0006986 9.16 HSPD1 HSPE1
3 protein folding GO:0006457 9.13 HSPD1 HSPE1 HSPE1-MOB4
4 positive regulation of inflammatory response GO:0050729 9.02 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 chaperone binding GO:0051087 8.62 HSPD1 HSPE1

Sources for Leukodystrophy, Hypomyelinating, 4

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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