MCID: LKD015
MIFTS: 44

Leukodystrophy, Hypomyelinating, 3

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Eye diseases, Fetal 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, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism and fish-eye disease, and has symptoms including paraparesis, spastic and abnormal pyramidal signs. 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 failure to thrive

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 55)
# Related Disease Score Top Affiliating Genes
1 leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism 10.5 AIMP1 POLR3A
2 fish-eye disease 10.1 APOA1 APOA2
3 hereditary amyloidosis 10.1 APOA1 APOA2
4 hepatic lipase deficiency 10.1 APOA1 APOE
5 cerebral atherosclerosis 10.1 APOA1 APOE
6 hypomyelinating leukodystrophy 9.9 AIMP1 POLR3A
7 amyloidosis aa 9.9 APOA1 LPA
8 aortic atherosclerosis 9.8 APOE LPA
9 xanthoma disseminatum 9.8 APOB APOE
10 hypercholesterolemia, autosomal dominant, type b 9.8 APOB APOE
11 defective apolipoprotein b-100 9.7 APOB APOE
12 dysbaric osteonecrosis 9.7 APOA1 APOB
13 familial lcat deficiency 9.7 APOA1 APOA2 APOE
14 homozygous familial hypercholesterolemia 9.6 APOB APOE
15 fetal macrosomia 9.6 APOA1 APOB
16 vitamin e, familial isolated deficiency of 9.5 APOA1 APOB
17 amyloidosis, familial visceral 9.5 APOA1 APOA2 LPA
18 chylomicron retention disease 9.5 APOA1 APOB
19 hypertriglyceridemia, familial 9.4 APOA1 APOB
20 schnyder corneal dystrophy 9.3 APOA2 APOB APOE
21 hypoalphalipoproteinemia, primary 9.3 APOA1 APOA2 APOB
22 hypobetalipoproteinemia, familial, 1 9.2 APOA1 APOB APOE
23 ischemic heart disease 9.2 APOA1 APOB APOE
24 abetalipoproteinemia 9.2 APOA1 APOB APOE
25 coronary stenosis 9.2 APOA1 APOB APOE
26 gallbladder disease 9.2 APOA1 APOB APOE
27 cerebrovascular disease 9.1 APOA1 APOB APOE
28 xanthomatosis 9.1 APOB APOE LPA
29 peripheral vascular disease 9.0 APOA1 APOB LPA
30 inherited metabolic disorder 9.0 APOA1 APOB
31 stroke, ischemic 8.9 APOB APOE LPA
32 diabetes mellitus, insulin-dependent 8.8 APOA1 APOB LPA
33 hyperlipoproteinemia, type iv 8.7 APOA1 APOA2 APOB APOE
34 hyperalphalipoproteinemia 1 8.7 APOA1 APOA2 APOB APOE
35 hypertension, essential 8.6 APOA1 APOB LPA
36 lipoprotein glomerulopathy 8.6 APOA2 APOB APOE LPA
37 hyperlipoproteinemia, type iii 8.5 APOA1 APOB APOE LPA
38 carotid artery disease 8.5 APOA1 APOB APOE LPA
39 familial hyperlipidemia 8.5 APOA1 APOB APOE LPA
40 lipid metabolism disorder 8.5 APOA1 APOB APOE LPA
41 arteries, anomalies of 8.5 APOA1 APOB APOE LPA
42 atherosclerosis susceptibility 8.5 APOA1 APOB APOE LPA
43 arteriosclerosis 8.5 APOA1 APOB APOE LPA
44 vascular disease 8.4 APOA1 APOB APOE LPA
45 hyperlipidemia, familial combined 8.0 APOA1 APOA2 APOB APOE LPA
46 hypolipoproteinemia 8.0 APOA1 APOA2 APOB APOE LPA
47 arcus corneae 8.0 APOA1 APOA2 APOB APOE LPA
48 lecithin:cholesterol acyltransferase deficiency 8.0 APOA1 APOA2 APOB APOE LPA
49 coronary heart disease 1 8.0 APOA1 APOA2 APOB APOE LPA
50 tangier disease 8.0 APOA1 APOA2 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 20)
# Description HPO Frequency HPO Source Accession
1 seizures 32 frequent (33%) HP:0001250
2 failure to thrive 32 HP:0001508
3 eeg abnormality 32 HP:0002353
4 abnormal pyramidal signs 32 HP:0007256
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 projectile vomiting 32 HP:0002587
19 sudanophilic leukodystrophy 32 HP:0003269
20 diffuse cerebral sclerosis 32 HP:0006918

UMLS symptoms related to Leukodystrophy, Hypomyelinating, 3:


paraparesis, spastic, abnormal pyramidal signs

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

Publications for Leukodystrophy, Hypomyelinating, 3

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

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 13)
# 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 11.38 APOA1 APOA2
8 11.19 APOB LPA
9
Show member pathways
11.14 APOA1 APOB
10
Show member pathways
11.09 APOA1 APOA2 APOB APOE LPA
11 10.87 APOA1 APOA2
12 10.81 APOA1 APOB
13 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 9.99 AIMP1 APOA1 APOA2 APOB APOE LPA
2 extracellular space GO:0005615 9.95 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 9.7 APOA1 APOA2 APOE
6 extracellular vesicle GO:1903561 9.56 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 46)
# Name GO ID Score Top Affiliating Genes
1 lipid metabolic process GO:0006629 9.97 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 steroid metabolic process GO:0008202 9.84 APOA1 APOB APOE
6 cholesterol metabolic process GO:0008203 9.84 APOA1 APOA2 APOB APOE
7 cholesterol homeostasis GO:0042632 9.83 APOA1 APOA2 APOB APOE
8 retinoid metabolic process GO:0001523 9.78 APOA1 APOA2 APOB APOE
9 lipid transport GO:0006869 9.77 APOA1 APOA2 APOB APOE LPA
10 cholesterol transport GO:0030301 9.75 APOA1 APOA2 APOB
11 triglyceride catabolic process GO:0019433 9.74 APOA1 APOB APOE
12 reverse cholesterol transport GO:0043691 9.73 APOA1 APOA2 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 9.7 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 triglyceride metabolic process GO:0006641 9.69 APOA2 APOE
19 high-density lipoprotein particle assembly GO:0034380 9.69 APOA1 APOA2 APOE
20 negative regulation of endothelial cell proliferation GO:0001937 9.68 AIMP1 APOE
21 phosphatidylcholine biosynthetic process GO:0006656 9.68 APOA1 APOA2
22 triglyceride homeostasis GO:0070328 9.68 APOA1 APOE
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 9.66 APOA1 APOE
27 neuron projection regeneration GO:0031102 9.65 APOA1 APOE
28 chylomicron remnant clearance GO:0034382 9.65 APOB APOE
29 regulation of cholesterol transport GO:0032374 9.64 APOA1 APOE
30 regulation of Cdc42 protein signal transduction GO:0032489 9.64 APOA1 APOE
31 peptidyl-methionine modification GO:0018206 9.63 APOA1 APOA2
32 negative regulation of cytokine secretion involved in immune response GO:0002740 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 lipoprotein catabolic process GO:0042159 9.61 APOB APOE
39 high-density lipoprotein particle clearance GO:0034384 9.61 APOA1 APOA2 APOE
40 protein oxidation GO:0018158 9.6 APOA1 APOA2
41 negative regulation of very-low-density lipoprotein particle remodeling GO:0010903 9.59 APOA1 APOA2
42 lipoprotein biosynthetic process GO:0042158 9.58 APOA1 APOB APOE
43 lipoprotein metabolic process GO:0042157 9.56 APOA1 APOA2 APOB APOE
44 low-density lipoprotein particle remodeling GO:0034374 9.46 APOA2 APOB APOE LPA
45 chylomicron assembly GO:0034378 9.26 APOA1 APOA2 APOB APOE
46 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 phosphatidylcholine binding GO:0031210 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 lipoprotein particle binding GO:0071813 9.48 APOA1 APOE
10 lipase inhibitor activity GO:0055102 9.46 APOA1 APOA2
11 high-density lipoprotein particle receptor binding GO:0070653 9.4 APOA1 APOA2
12 apolipoprotein receptor binding GO:0034190 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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