HLD3
MCID: LKD015
MIFTS: 46

Leukodystrophy, Hypomyelinating, 3 (HLD3)

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

Aliases & Classifications for Leukodystrophy, Hypomyelinating, 3

MalaCards integrated aliases for Leukodystrophy, Hypomyelinating, 3:

Name: Leukodystrophy, Hypomyelinating, 3 58 76 13
Leukodystrophy, Hypomyelinating 3 54 30 6
Hld3 58 12 76
Pelizaeus-Merzbacher-Like Disease Due to Aimp1 Mutation 12 60
Hypomyelinating Leukodystrophy 3 12 15
Pelizaeus-Merzbacher-Like Disease, Autosomal Recessive, 2 74
Leukodystrophy, Hypomyelinating, Type 3 41
Perinatal Sudanophilic Leukodystrophy 54

Characteristics:

Orphanet epidemiological data:

60
pelizaeus-merzbacher-like disease due to aimp1 mutation
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal; Age of death: early childhood;

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
onset in first months of life
nystagmus is often the presenting sign


HPO:

33
leukodystrophy, hypomyelinating, 3:
Mortality/Aging death in infancy
Onset and clinical course progressive
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 60  
Rare neurological diseases


Summaries for Leukodystrophy, Hypomyelinating, 3

OMIM : 58 Autosomal recessive hypomyelinating leukodystrophy-3 (HLD3) is a severe neurologic disorder characterized by early infantile onset of global developmental delay, lack of development, lack of speech acquisition, and peripheral spasticity associated with decreased myelination in the central nervous system (summary by Feinstein et al., 2010). The disorder is phenotypically similar to X-linked Pelizaeus-Merzbacher disease (PMD; 312080), which is caused by mutation in the PLP1 gene (300401). For a general phenotypic description and a discussion of genetic heterogeneity of HLD, see 312080. (260600)

MalaCards based summary : Leukodystrophy, Hypomyelinating, 3, also known as leukodystrophy, hypomyelinating 3, is related to leukodystrophy and leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism, and has symptoms including abnormal pyramidal signs and paraparesis, spastic. An important gene associated with Leukodystrophy, Hypomyelinating, 3 is AIMP1 (Aminoacyl TRNA Synthetase Complex Interacting Multifunctional Protein 1), and among its related pathways/superpathways are Metabolism and Metabolism of water-soluble vitamins and cofactors. Affiliated tissues include brain, and related phenotypes are seizures and nystagmus

Disease Ontology : 12 A hypomyelinating leukodystrophy characterized by autosomal recessive inheritance of early infantile onset of global developmental delay, lack of development, lack of speech acquisition, and peripheral spasticity associated with decreased myelination in the central nervous system that has material basis in homozygous mutation in the AIMP1 gene on chromosome 4q24.

UniProtKB/Swiss-Prot : 76 Leukodystrophy, hypomyelinating, 3: A severe autosomal recessive hypomyelinating leukodystrophy characterized by early infantile onset of global developmental delay, lack of development, lack of speech acquisition, and peripheral spasticity associated with decreased myelination in the central nervous system.

Related Diseases for Leukodystrophy, Hypomyelinating, 3

Diseases in the Hypomyelinating Leukodystrophy family:

Leukodystrophy, Hypomyelinating, 3 Leukodystrophy, Hypomyelinating, 2
Leukodystrophy, Hypomyelinating, 5 Leukodystrophy, Hypomyelinating, 4
Leukodystrophy, Hypomyelinating, 6 Leukodystrophy, Hypomyelinating, 9
Leukodystrophy, Hypomyelinating, 10 Leukodystrophy, Hypomyelinating, 11
Leukodystrophy, Hypomyelinating, 12 Leukodystrophy, Hypomyelinating, 13
Leukodystrophy, Hypomyelinating, 14 Leukodystrophy, Hypomyelinating, 15
Leukodystrophy, Hypomyelinating, 16 Leukodystrophy, Hypomyelinating, 17

Diseases related to Leukodystrophy, Hypomyelinating, 3 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 54)
# Related Disease Score Top Affiliating Genes
1 leukodystrophy 10.5
2 leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism 10.2 AIMP1 POLR3A
3 hypomyelinating leukodystrophy 10.0 AIMP1 POLR3A
4 hepatic lipase deficiency 10.0 APOA1 APOE
5 cerebral atherosclerosis 10.0 APOA1 APOE
6 fish-eye disease 10.0 APOA1 APOA2
7 hereditary amyloidosis 10.0 APOA1 APOA2
8 xanthoma disseminatum 9.9 APOB APOE
9 hypercholesterolemia, autosomal dominant, type b 9.9 APOB APOE
10 defective apolipoprotein b-100 9.9 APOB APOE
11 amyloidosis, familial visceral 9.9 APOA1 APOA2
12 huntington disease-like 1 9.9 APOB APOE
13 hyperlipoproteinemia, type iv 9.8 APOA2 APOB
14 sea-blue histiocyte disease 9.8 APOB APOE
15 homozygous familial hypercholesterolemia 9.8 APOB APOE
16 dysbaric osteonecrosis 9.8 APOA1 APOB
17 xanthomatosis 9.8 APOB APOE
18 fetal macrosomia 9.8 APOA1 APOB
19 familial lcat deficiency 9.7 APOA1 APOA2 APOE
20 chylomicron retention disease 9.7 APOA1 APOB
21 vitamin e, familial isolated deficiency of 9.7 APOA1 APOB
22 hypobetalipoproteinemia, familial, 2 9.7 APOA1 APOB
23 lipoprotein glomerulopathy 9.6 APOA2 APOB APOE
24 schnyder corneal dystrophy 9.6 APOA2 APOB APOE
25 inherited metabolic disorder 9.6 APOA1 APOB
26 hyperlipoproteinemia, type v 9.6 APOA1 APOB APOE
27 hyperlipidemia, familial combined 9.6 APOA1 APOA2 APOB
28 ischemic heart disease 9.6 APOA1 APOB APOE
29 hypoalphalipoproteinemia, primary 9.6 APOA1 APOA2 APOB
30 hypertriglyceridemia, familial 9.6 APOA1 APOB APOE
31 hyperlipoproteinemia, type iii 9.6 APOA1 APOB APOE
32 peripheral vascular disease 9.6 APOA1 APOB
33 coronary stenosis 9.6 APOA1 APOB APOE
34 carotid artery disease 9.6 APOA1 APOB APOE
35 gallbladder disease 9.5 APOA1 APOB APOE
36 abetalipoproteinemia 9.5 APOA1 APOB APOE
37 familial hyperlipidemia 9.5 APOA1 APOB APOE
38 arteries, anomalies of 9.5 APOA1 APOB APOE
39 lipid metabolism disorder 9.5 APOA1 APOB APOE
40 atherosclerosis susceptibility 9.5 APOA1 APOB APOE
41 arteriosclerosis 9.5 APOA1 APOB APOE
42 cerebrovascular disease 9.5 APOA1 APOB APOE
43 vascular disease 9.5 APOA1 APOB APOE
44 acquired metabolic disease 9.4 APOA1 APOB
45 hypolipoproteinemia 9.3 APOA1 APOA2 APOB APOE
46 arcus corneae 9.3 APOA1 APOA2 APOB APOE
47 hyperalphalipoproteinemia 1 9.3 APOA1 APOA2 APOB APOE
48 lecithin:cholesterol acyltransferase deficiency 9.3 APOA1 APOA2 APOB APOE
49 tangier disease 9.3 APOA1 APOA2 APOB APOE
50 coronary heart disease 1 9.3 APOA1 APOA2 APOB APOE

Graphical network of the top 20 diseases related to Leukodystrophy, Hypomyelinating, 3:



Diseases related to Leukodystrophy, Hypomyelinating, 3

Symptoms & Phenotypes for Leukodystrophy, Hypomyelinating, 3

Human phenotypes related to Leukodystrophy, Hypomyelinating, 3:

33 (show all 21)
# Description HPO Frequency HPO Source Accession
1 seizures 33 frequent (33%) HP:0001250
2 nystagmus 33 HP:0000639
3 failure to thrive 33 HP:0001508
4 eeg abnormality 33 HP:0002353
5 coarse facial features 33 HP:0000280
6 global developmental delay 33 HP:0001263
7 microcephaly 33 HP:0000252
8 visual impairment 33 HP:0000505
9 arthrogryposis multiplex congenita 33 HP:0002804
10 kyphoscoliosis 33 HP:0002751
11 premature birth 33 HP:0001622
12 corpus callosum atrophy 33 HP:0007371
13 leukodystrophy 33 HP:0002415
14 progressive flexion contractures 33 HP:0005876
15 spastic paraparesis 33 HP:0002313
16 muscular hypotonia of the trunk 33 HP:0008936
17 global brain atrophy 33 HP:0002283
18 abnormal pyramidal sign 33 HP:0007256
19 projectile vomiting 33 HP:0002587
20 sudanophilic leukodystrophy 33 HP:0003269
21 diffuse cerebral sclerosis 33 HP:0006918

Symptoms via clinical synopsis from OMIM:

58
Growth Other:
failure to thrive

Skeletal Spine:
kyphoscoliosis

Head And Neck Face:
coarse facies

Head And Neck Eyes:
impaired vision
horizontal or rotary nystagmus
pale fundi
slow pupillary reflexes

Head And Neck Head:
microcephaly

Neurologic Central Nervous System:
spastic paraparesis
pyramidal signs
abnormal eeg
atrophy of the corpus callosum
axial hypotonia
more
Skeletal:
joint contractures, progressive

Muscle Soft Tissue:
atrophy of the lower limbs

Clinical features from OMIM:

260600

UMLS symptoms related to Leukodystrophy, Hypomyelinating, 3:


abnormal pyramidal signs, paraparesis, spastic

GenomeRNAi Phenotypes related to Leukodystrophy, Hypomyelinating, 3 according to GeneCards Suite gene sharing:

27
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased free cholesterol GR00340-A-2 9.13 APOA1 APOB APOE
2 Increased LDL uptake GR00340-A-1 8.62 APOA1 APOE

Drugs & Therapeutics for Leukodystrophy, Hypomyelinating, 3

Search Clinical Trials , NIH Clinical Center for Leukodystrophy, Hypomyelinating, 3

Genetic Tests for Leukodystrophy, Hypomyelinating, 3

Genetic tests related to Leukodystrophy, Hypomyelinating, 3:

# Genetic test Affiliating Genes
1 Leukodystrophy, Hypomyelinating 3 30 AIMP1

Anatomical Context for Leukodystrophy, Hypomyelinating, 3

MalaCards organs/tissues related to Leukodystrophy, Hypomyelinating, 3:

42
Brain

Publications for Leukodystrophy, Hypomyelinating, 3

Articles related to Leukodystrophy, Hypomyelinating, 3:

# Title Authors Year
1
Neurochemical findings in a perinatal sudanophilic leukodystrophy rich in steryl ester. ( 978227 )
1976
2
Correspondence: Lipid analysis of perinatal sudanophilic leukodystrophy. ( 4810283 )
1974
3
Perinatal sudanophilic leukodystrophy. ( 4685841 )
1973

Variations for Leukodystrophy, Hypomyelinating, 3

ClinVar genetic disease variations for Leukodystrophy, Hypomyelinating, 3:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 AIMP1 NM_001142415.1(AIMP1): c.115C> T (p.Gln39Ter) single nucleotide variant Pathogenic rs724159969 GRCh37 Chromosome 4, 107248613: 107248613
2 AIMP1 NM_001142415.1(AIMP1): c.115C> T (p.Gln39Ter) single nucleotide variant Pathogenic rs724159969 GRCh38 Chromosome 4, 106327456: 106327456
3 AIMP1 NM_001142415.1(AIMP1): c.292_293delCA (p.Gln98Valfs) deletion Pathogenic rs387906865 GRCh37 Chromosome 4, 107249301: 107249302
4 AIMP1 NM_001142415.1(AIMP1): c.292_293delCA (p.Gln98Valfs) deletion Pathogenic rs387906865 GRCh38 Chromosome 4, 106328144: 106328145
5 AIMP1 NM_001142415.1(AIMP1): c.334C> T (p.Gln112Ter) single nucleotide variant Pathogenic rs879253867 GRCh37 Chromosome 4, 107249343: 107249343
6 AIMP1 NM_001142415.1(AIMP1): c.334C> T (p.Gln112Ter) single nucleotide variant Pathogenic rs879253867 GRCh38 Chromosome 4, 106328186: 106328186
7 AIMP1 NM_001142416.1(AIMP1): c.976A> G (p.Arg326Gly) single nucleotide variant not provided GRCh37 Chromosome 4, 107268814: 107268814
8 AIMP1 NM_001142416.1(AIMP1): c.976A> G (p.Arg326Gly) single nucleotide variant not provided GRCh38 Chromosome 4, 106347657: 106347657
9 AIMP1 NM_001142415.1(AIMP1): c.162delA (p.Lys54Asnfs) deletion Pathogenic GRCh37 Chromosome 4, 107248660: 107248660
10 AIMP1 NM_001142415.1(AIMP1): c.162delA (p.Lys54Asnfs) deletion Pathogenic GRCh38 Chromosome 4, 106327503: 106327503

Expression for Leukodystrophy, Hypomyelinating, 3

Search GEO for disease gene expression data for Leukodystrophy, Hypomyelinating, 3.

Pathways for Leukodystrophy, Hypomyelinating, 3

Pathways related to Leukodystrophy, Hypomyelinating, 3 according to GeneCards Suite gene sharing:

(show all 12)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.54 AIMP1 AIMP2 APOA1 APOA2 APOB APOE
2
Show member pathways
12.17 APOA1 APOA2 APOB APOE
3
Show member pathways
11.99 APOA1 APOA2 APOB APOE
4
Show member pathways
11.97 APOA1 APOB APOE
5
Show member pathways
11.59 APOA1 APOA2 APOB APOE
6
Show member pathways
11.51 APOA1 APOB APOE
7 11.38 APOA1 APOA2
8
Show member pathways
11.14 APOA1 APOB
9
Show member pathways
11 APOA1 APOA2 APOB APOE
10 10.89 APOA1 APOA2
11 10.81 APOA1 APOB
12 10.68 APOA1 APOA2

GO Terms for Leukodystrophy, Hypomyelinating, 3

Cellular components related to Leukodystrophy, Hypomyelinating, 3 according to GeneCards Suite gene sharing:

(show all 16)
# Name GO ID Score Top Affiliating Genes
1 extracellular region GO:0005576 9.96 AIMP1 APOA1 APOA2 APOB APOE
2 extracellular space GO:0005615 9.92 AIMP1 APOA1 APOA2 APOB APOE
3 endoplasmic reticulum lumen GO:0005788 9.76 APOA1 APOA2 APOB APOE
4 early endosome GO:0005769 9.73 APOA1 APOA2 APOB APOE
5 blood microparticle GO:0072562 9.69 APOA1 APOA2 APOE
6 extracellular vesicle GO:1903561 9.55 APOA1 APOE
7 clathrin-coated endocytic vesicle membrane GO:0030669 9.54 APOB APOE
8 high-density lipoprotein particle GO:0034364 9.54 APOA1 APOA2 APOE
9 endocytic vesicle lumen GO:0071682 9.5 APOA1 APOB APOE
10 aminoacyl-tRNA synthetase multienzyme complex GO:0017101 9.49 AIMP1 AIMP2
11 spherical high-density lipoprotein particle GO:0034366 9.48 APOA1 APOA2
12 low-density lipoprotein particle GO:0034362 9.43 APOA1 APOB APOE
13 discoidal high-density lipoprotein particle GO:0034365 9.4 APOA1 APOE
14 intermediate-density lipoprotein particle GO:0034363 9.33 APOA1 APOB APOE
15 very-low-density lipoprotein particle GO:0034361 9.26 APOA1 APOA2 APOB APOE
16 chylomicron GO:0042627 8.92 APOA1 APOA2 APOB APOE

Biological processes related to Leukodystrophy, Hypomyelinating, 3 according to GeneCards Suite gene sharing:

(show all 44)
# Name GO ID Score Top Affiliating Genes
1 post-translational protein modification GO:0043687 9.92 APOA1 APOA2 APOB APOE
2 cellular protein metabolic process GO:0044267 9.88 APOA1 APOA2 APOB APOE
3 lipid transport GO:0006869 9.86 APOA1 APOA2 APOB APOE
4 receptor-mediated endocytosis GO:0006898 9.85 APOA1 APOB APOE
5 steroid metabolic process GO:0008202 9.83 APOA1 APOB APOE
6 cholesterol homeostasis GO:0042632 9.83 APOA1 APOA2 APOB APOE
7 cholesterol metabolic process GO:0008203 9.8 APOA1 APOA2 APOB APOE
8 cholesterol transport GO:0030301 9.75 APOA1 APOA2 APOB
9 triglyceride catabolic process GO:0019433 9.74 APOA1 APOB APOE
10 reverse cholesterol transport GO:0043691 9.72 APOA1 APOA2 APOE
11 high-density lipoprotein particle remodeling GO:0034375 9.71 APOA1 APOA2 APOE
12 response to estrogen GO:0043627 9.69 APOA1 APOA2
13 animal organ regeneration GO:0031100 9.69 APOA1 APOA2
14 tRNA aminoacylation for protein translation GO:0006418 9.69 AIMP1 AIMP2
15 low-density lipoprotein particle remodeling GO:0034374 9.69 APOA2 APOB APOE
16 cholesterol biosynthetic process GO:0006695 9.68 APOA1 APOE
17 negative regulation of endothelial cell proliferation GO:0001937 9.68 AIMP1 APOE
18 triglyceride metabolic process GO:0006641 9.68 APOA2 APOE
19 triglyceride homeostasis GO:0070328 9.68 APOA1 APOE
20 phosphatidylcholine biosynthetic process GO:0006656 9.67 APOA1 APOA2
21 artery morphogenesis GO:0048844 9.67 APOB APOE
22 retinoid metabolic process GO:0001523 9.67 APOA1 APOA2 APOB APOE
23 positive regulation of lipid biosynthetic process GO:0046889 9.66 APOA1 APOE
24 very-low-density lipoprotein particle remodeling GO:0034372 9.65 APOA1 APOE
25 chylomicron remnant clearance GO:0034382 9.65 APOB APOE
26 regulation of Cdc42 protein signal transduction GO:0032489 9.65 APOA1 APOE
27 high-density lipoprotein particle assembly GO:0034380 9.65 APOA1 APOA2 APOE
28 regulation of cholesterol transport GO:0032374 9.64 APOA1 APOE
29 negative regulation of cytokine secretion involved in immune response GO:0002740 9.64 APOA1 APOA2
30 peptidyl-methionine modification GO:0018206 9.63 APOA1 APOA2
31 very-low-density lipoprotein particle clearance GO:0034447 9.63 APOB APOE
32 phospholipid efflux GO:0033700 9.63 APOA1 APOA2 APOE
33 regulation of intestinal cholesterol absorption GO:0030300 9.62 APOA1 APOA2
34 negative regulation of lipase activity GO:0060192 9.61 APOA1 APOA2
35 protein oxidation GO:0018158 9.61 APOA1 APOA2
36 high-density lipoprotein particle clearance GO:0034384 9.61 APOA1 APOA2 APOE
37 lipoprotein catabolic process GO:0042159 9.6 APOB APOE
38 negative regulation of very-low-density lipoprotein particle remodeling GO:0010903 9.59 APOA1 APOA2
39 positive regulation of cholesterol esterification GO:0010873 9.58 APOA1 APOA2 APOE
40 cholesterol efflux GO:0033344 9.56 APOA1 APOA2 APOB APOE
41 lipoprotein biosynthetic process GO:0042158 9.5 APOA1 APOB APOE
42 lipoprotein metabolic process GO:0042157 9.46 APOA1 APOA2 APOB APOE
43 chylomicron assembly GO:0034378 9.26 APOA1 APOA2 APOB APOE
44 chylomicron remodeling GO:0034371 8.92 APOA1 APOA2 APOB APOE

Molecular functions related to Leukodystrophy, Hypomyelinating, 3 according to GeneCards Suite gene sharing:

(show all 14)
# Name GO ID Score Top Affiliating Genes
1 lipid binding GO:0008289 9.61 APOA1 APOA2 APOE
2 phospholipid binding GO:0005543 9.56 APOA1 APOA2 APOB APOE
3 amyloid-beta binding GO:0001540 9.54 APOA1 APOE
4 heat shock protein binding GO:0031072 9.52 APOA1 APOA2
5 low-density lipoprotein particle receptor binding GO:0050750 9.51 APOB APOE
6 cholesterol binding GO:0015485 9.5 APOA1 APOA2 APOE
7 high-density lipoprotein particle binding GO:0008035 9.49 APOA1 APOA2
8 lipase inhibitor activity GO:0055102 9.48 APOA1 APOA2
9 lipoprotein particle binding GO:0071813 9.46 APOA1 APOE
10 apolipoprotein receptor binding GO:0034190 9.4 APOA1 APOA2
11 high-density lipoprotein particle receptor binding GO:0070653 9.37 APOA1 APOA2
12 phosphatidylcholine-sterol O-acyltransferase activator activity GO:0060228 9.33 APOA1 APOA2 APOE
13 lipid transporter activity GO:0005319 9.26 APOA1 APOA2 APOB APOE
14 cholesterol transporter activity GO:0017127 8.92 APOA1 APOA2 APOB APOE

Sources for Leukodystrophy, Hypomyelinating, 3

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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