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 57 75 13
Leukodystrophy, Hypomyelinating 3 53 29 6
Hld3 57 12 75
Pelizaeus-Merzbacher-Like Disease Due to Aimp1 Mutation 12 59
Hypomyelinating Leukodystrophy 3 12 15
Pelizaeus-Merzbacher-Like Disease, Autosomal Recessive, 2 73
Leukodystrophy, Hypomyelinating, Type 3 40
Perinatal Sudanophilic Leukodystrophy 53

Characteristics:

Orphanet epidemiological data:

59
pelizaeus-merzbacher-like disease due to aimp1 mutation
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal; Age of death: early childhood;

OMIM:

57
Inheritance:
autosomal recessive

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


HPO:

32
leukodystrophy, hypomyelinating, 3:
Mortality/Aging death in infancy
Onset and clinical course progressive
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 59  
Rare neurological diseases


Summaries for Leukodystrophy, Hypomyelinating, 3

OMIM : 57 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, eye and heart, and related phenotypes are nystagmus and seizures

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 : 75 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 60)
# Related Disease Score Top Affiliating Genes
1 leukodystrophy 10.3
2 leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism 10.1 AIMP1 POLR3A
3 fish-eye disease 10.0 APOA1 APOA2
4 hereditary amyloidosis 10.0 APOA1 APOA2
5 hepatic lipase deficiency 10.0 APOA1 APOE
6 cerebral atherosclerosis 10.0 APOA1 APOE
7 amyloidosis aa 10.0 APOA1 LPA
8 hypomyelinating leukodystrophy 10.0 AIMP1 POLR3A
9 aortic atherosclerosis 9.9 APOE LPA
10 xanthoma disseminatum 9.9 APOB APOE
11 hyperlipoproteinemia, type iv 9.9 APOA2 APOB
12 hypercholesterolemia, autosomal dominant, type b 9.9 APOB APOE
13 defective apolipoprotein b-100 9.9 APOB APOE
14 familial lcat deficiency 9.9 APOA1 APOA2 APOE
15 sea-blue histiocyte disease 9.9 APOB APOE
16 dysbaric osteonecrosis 9.9 APOA1 APOB
17 homozygous familial hypercholesterolemia 9.9 APOB APOE
18 niemann-pick disease, type b 9.9 APOA1 LPA
19 fetal macrosomia 9.9 APOA1 APOB
20 chylomicron retention disease 9.8 APOA1 APOB
21 amyloidosis, familial visceral 9.8 APOA1 APOA2 LPA
22 vitamin e, familial isolated deficiency of 9.8 APOA1 APOB
23 schnyder corneal dystrophy 9.8 APOA2 APOB APOE
24 hypoalphalipoproteinemia, primary 9.8 APOA1 APOA2 APOB
25 hyperlipoproteinemia, type v 9.8 APOA1 APOB APOE
26 ischemic heart disease 9.8 APOA1 APOB APOE
27 hypertriglyceridemia, familial 9.7 APOA1 APOB APOE
28 coronary stenosis 9.7 APOA1 APOB APOE
29 abetalipoproteinemia 9.7 APOA1 APOB APOE
30 gallbladder disease 9.7 APOA1 APOB APOE
31 cerebrovascular disease 9.7 APOA1 APOB APOE
32 huntington disease-like 1 9.7 APOB APOE LPA
33 hypobetalipoproteinemia, familial, 2 9.7 APOA1 APOB LPA
34 xanthomatosis 9.7 APOB APOE LPA
35 peripheral vascular disease 9.7 APOA1 APOB LPA
36 coronary artery anomaly 9.7 APOA1 APOB LPA
37 inherited metabolic disorder 9.7 APOA1 APOB
38 stroke, ischemic 9.7 APOB APOE LPA
39 diabetes mellitus, insulin-dependent 9.6 APOA1 APOB LPA
40 hyperalphalipoproteinemia 1 9.6 APOA1 APOA2 APOB APOE
41 hypertension, essential 9.6 APOA1 APOB LPA
42 lipoprotein glomerulopathy 9.6 APOA2 APOB APOE LPA
43 hyperlipidemia, familial combined 9.6 APOA1 APOA2 APOB LPA
44 hyperlipoproteinemia, type iii 9.5 APOA1 APOB APOE LPA
45 carotid artery disease 9.5 APOA1 APOB APOE LPA
46 familial hyperlipidemia 9.5 APOA1 APOB APOE LPA
47 arteries, anomalies of 9.5 APOA1 APOB APOE LPA
48 lipid metabolism disorder 9.5 APOA1 APOB APOE LPA
49 atherosclerosis susceptibility 9.5 APOA1 APOB APOE LPA
50 arteriosclerosis 9.5 APOA1 APOB APOE LPA

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



Diseases related to Leukodystrophy, Hypomyelinating, 3

Symptoms & Phenotypes for Leukodystrophy, Hypomyelinating, 3

Symptoms via clinical synopsis from OMIM:

57
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

Human phenotypes related to Leukodystrophy, Hypomyelinating, 3:

32 (show all 21)
# Description HPO Frequency HPO Source Accession
1 nystagmus 32 HP:0000639
2 seizures 32 frequent (33%) HP:0001250
3 failure to thrive 32 HP:0001508
4 eeg abnormality 32 HP:0002353
5 coarse facial features 32 HP:0000280
6 global developmental delay 32 HP:0001263
7 microcephaly 32 HP:0000252
8 visual impairment 32 HP:0000505
9 arthrogryposis multiplex congenita 32 HP:0002804
10 premature birth 32 HP:0001622
11 corpus callosum atrophy 32 HP:0007371
12 kyphoscoliosis 32 HP:0002751
13 leukodystrophy 32 HP:0002415
14 progressive flexion contractures 32 HP:0005876
15 spastic paraparesis 32 HP:0002313
16 muscular hypotonia of the trunk 32 HP:0008936
17 global brain atrophy 32 HP:0002283
18 abnormal pyramidal sign 32 HP:0007256
19 projectile vomiting 32 HP:0002587
20 sudanophilic leukodystrophy 32 HP:0003269
21 diffuse cerebral sclerosis 32 HP:0006918

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:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased free cholesterol GR00340-A-2 9.26 APOA1 APOB APOE LPA
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 29 AIMP1

Anatomical Context for Leukodystrophy, Hypomyelinating, 3

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

41
Brain, Eye, Heart

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

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.292_293delCA (p.Gln98Valfs) deletion Pathogenic rs387906865 GRCh37 Chromosome 4, 107249301: 107249302
2 AIMP1 NM_001142415.1(AIMP1): c.292_293delCA (p.Gln98Valfs) deletion Pathogenic rs387906865 GRCh38 Chromosome 4, 106328144: 106328145
3 AIMP1 NM_001142415.1(AIMP1): c.115C> T (p.Gln39Ter) single nucleotide variant Pathogenic rs724159969 GRCh37 Chromosome 4, 107248613: 107248613
4 AIMP1 NM_001142415.1(AIMP1): c.115C> T (p.Gln39Ter) single nucleotide variant Pathogenic rs724159969 GRCh38 Chromosome 4, 106327456: 106327456
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

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
13.49 AIMP1 AIMP2 APOA1 APOA2 APOB APOE
2
Show member pathways
12.28 APOA1 APOA2 APOB APOE
3
Show member pathways
11.99 APOA1 APOB APOE
4
Show member pathways
11.89 APOA1 APOA2 APOB APOE LPA
5
Show member pathways
11.79 APOA1 APOA2 APOB APOE
6
Show member pathways
11.51 APOA1 APOB APOE
7 11.19 APOB LPA
8
Show member pathways
11.14 APOA1 APOB
9
Show member pathways
11.09 APOA1 APOA2 APOB APOE LPA
10 10.87 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 space GO:0005615 9.95 AIMP1 APOA1 APOA2 APOB APOE
2 endoplasmic reticulum lumen GO:0005788 9.76 APOA1 APOA2 APOB APOE
3 early endosome GO:0005769 9.73 APOA1 APOA2 APOB APOE
4 blood microparticle GO:0072562 9.69 APOA1 APOA2 APOE
5 extracellular vesicle GO:1903561 9.56 APOA1 APOE
6 clathrin-coated endocytic vesicle membrane GO:0030669 9.54 APOB APOE
7 high-density lipoprotein particle GO:0034364 9.54 APOA1 APOA2 APOE
8 endocytic vesicle lumen GO:0071682 9.5 APOA1 APOB APOE
9 aminoacyl-tRNA synthetase multienzyme complex GO:0017101 9.49 AIMP1 AIMP2
10 spherical high-density lipoprotein particle GO:0034366 9.48 APOA1 APOA2
11 low-density lipoprotein particle GO:0034362 9.43 APOA1 APOB APOE
12 discoidal high-density lipoprotein particle GO:0034365 9.4 APOA1 APOE
13 intermediate-density lipoprotein particle GO:0034363 9.33 APOA1 APOB APOE
14 very-low-density lipoprotein particle GO:0034361 9.26 APOA1 APOA2 APOB APOE
15 chylomicron GO:0042627 8.92 APOA1 APOA2 APOB APOE
16 extracellular region GO:0005576 10 AIMP1 APOA1 APOA2 APOB APOE LPA

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

(show all 45)
# Name GO ID Score Top Affiliating Genes
1 lipid metabolic process GO:0006629 9.96 APOA1 APOB APOE LPA
2 post-translational protein modification GO:0043687 9.95 APOA1 APOA2 APOB APOE
3 cellular protein metabolic process GO:0044267 9.88 APOA1 APOA2 APOB APOE
4 receptor-mediated endocytosis GO:0006898 9.85 APOA1 APOB APOE
5 cholesterol homeostasis GO:0042632 9.84 APOA1 APOA2 APOB APOE
6 steroid metabolic process GO:0008202 9.83 APOA1 APOB APOE
7 cholesterol metabolic process GO:0008203 9.83 APOA1 APOA2 APOB APOE
8 lipid transport GO:0006869 9.77 APOA1 APOA2 APOB APOE LPA
9 cholesterol transport GO:0030301 9.75 APOA1 APOA2 APOB
10 triglyceride catabolic process GO:0019433 9.74 APOA1 APOB APOE
11 reverse cholesterol transport GO:0043691 9.73 APOA1 APOA2 APOE
12 retinoid metabolic process GO:0001523 9.73 APOA1 APOA2 APOB APOE
13 high-density lipoprotein particle remodeling GO:0034375 9.72 APOA1 APOA2 APOE
14 response to estrogen GO:0043627 9.7 APOA1 APOA2
15 animal organ regeneration GO:0031100 9.69 APOA1 APOA2
16 tRNA aminoacylation for protein translation GO:0006418 9.69 AIMP1 AIMP2
17 cholesterol biosynthetic process GO:0006695 9.69 APOA1 APOE
18 high-density lipoprotein particle assembly GO:0034380 9.69 APOA1 APOA2 APOE
19 negative regulation of endothelial cell proliferation GO:0001937 9.68 AIMP1 APOE
20 triglyceride metabolic process GO:0006641 9.68 APOA2 APOE
21 triglyceride homeostasis GO:0070328 9.68 APOA1 APOE
22 phosphatidylcholine biosynthetic process GO:0006656 9.68 APOA1 APOA2
23 artery morphogenesis GO:0048844 9.67 APOB APOE
24 positive regulation of lipid biosynthetic process GO:0046889 9.67 APOA1 APOE
25 phospholipid efflux GO:0033700 9.67 APOA1 APOA2 APOE
26 very-low-density lipoprotein particle remodeling GO:0034372 9.65 APOA1 APOE
27 chylomicron remnant clearance GO:0034382 9.65 APOB APOE
28 high-density lipoprotein particle clearance GO:0034384 9.65 APOA1 APOA2 APOE
29 regulation of Cdc42 protein signal transduction GO:0032489 9.64 APOA1 APOE
30 regulation of cholesterol transport GO:0032374 9.64 APOA1 APOE
31 negative regulation of cytokine secretion involved in immune response GO:0002740 9.63 APOA1 APOA2
32 peptidyl-methionine modification GO:0018206 9.63 APOA1 APOA2
33 positive regulation of cholesterol esterification GO:0010873 9.63 APOA1 APOA2 APOE
34 very-low-density lipoprotein particle clearance GO:0034447 9.62 APOB APOE
35 regulation of intestinal cholesterol absorption GO:0030300 9.62 APOA1 APOA2
36 cholesterol efflux GO:0033344 9.62 APOA1 APOA2 APOB APOE
37 negative regulation of lipase activity GO:0060192 9.61 APOA1 APOA2
38 protein oxidation GO:0018158 9.61 APOA1 APOA2
39 lipoprotein catabolic process GO:0042159 9.6 APOB APOE
40 negative regulation of very-low-density lipoprotein particle remodeling GO:0010903 9.59 APOA1 APOA2
41 lipoprotein biosynthetic process GO:0042158 9.58 APOA1 APOB APOE
42 lipoprotein metabolic process GO:0042157 9.56 APOA1 APOA2 APOB APOE
43 low-density lipoprotein particle remodeling GO:0034374 9.46 APOA2 APOB APOE LPA
44 chylomicron assembly GO:0034378 9.26 APOA1 APOA2 APOB APOE
45 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 15)
# Name GO ID Score Top Affiliating Genes
1 lipid binding GO:0008289 9.73 APOA1 APOA2 APOB APOE
2 heparin binding GO:0008201 9.69 APOB APOE LPA
3 phospholipid binding GO:0005543 9.56 APOA1 APOA2 APOB APOE
4 amyloid-beta binding GO:0001540 9.55 APOA1 APOE
5 heat shock protein binding GO:0031072 9.54 APOA1 APOA2
6 low-density lipoprotein particle receptor binding GO:0050750 9.52 APOB APOE
7 cholesterol binding GO:0015485 9.5 APOA1 APOA2 APOE
8 high-density lipoprotein particle binding GO:0008035 9.49 APOA1 APOA2
9 lipase inhibitor activity GO:0055102 9.48 APOA1 APOA2
10 lipoprotein particle binding GO:0071813 9.46 APOA1 APOE
11 apolipoprotein receptor binding GO:0034190 9.4 APOA1 APOA2
12 high-density lipoprotein particle receptor binding GO:0070653 9.37 APOA1 APOA2
13 phosphatidylcholine-sterol O-acyltransferase activator activity GO:0060228 9.33 APOA1 APOA2 APOE
14 lipid transporter activity GO:0005319 9.26 APOA1 APOA2 APOB APOE
15 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 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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