MCID: LKD015
MIFTS: 44

Leukodystrophy, Hypomyelinating, 3

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

Aliases & Classifications for Leukodystrophy, Hypomyelinating, 3

MalaCards integrated aliases for Leukodystrophy, Hypomyelinating, 3:

Name: Leukodystrophy, Hypomyelinating, 3 53 71 13
Hld3 53 12 71
Pelizaeus-Merzbacher-Like Disease Due to Aimp1 Mutation 12 55
Leukodystrophy, Hypomyelinating 3 49 28
Hypomyelinating Leukodystrophy 3 12 14
Pelizaeus-Merzbacher-Like Disease, Autosomal Recessive, 2 69
Perinatal Sudanophilic Leukodystrophy 49

Characteristics:

Orphanet epidemiological data:

55
pelizaeus-merzbacher-like disease due to aimp1 mutation
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal; Age of death: early childhood;

OMIM:

53
Inheritance:
autosomal recessive

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


HPO:

31
leukodystrophy, hypomyelinating, 3:
Mortality/Aging death in infancy
Onset and clinical course progressive
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 55  
Rare neurological diseases


Summaries for Leukodystrophy, Hypomyelinating, 3

OMIM : 53 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 hld3, is related to leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism and fish-eye disease, and has symptoms including seizures, abnormal pyramidal signs and failure to thrive. 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 Decreased free cholesterol and Increased LDL uptake

UniProtKB/Swiss-Prot : 71 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.

NIH Rare Diseases : 49 This condition doesn't have a summary yet. Please see our page(s) on Leukodystrophy.

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.

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

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 10.3 AIMP1 POLR3A
2 fish-eye disease 10.1 APOA1 APOA2
3 hereditary amyloidosis 10.0 APOA1 APOA2
4 hepatic lipase deficiency 10.0 APOA1 APOE
5 cerebral atherosclerosis 10.0 APOA1 APOE
6 hypomyelinating leukodystrophy 10.0 AIMP1 POLR3A
7 amyloidosis aa 9.9 APOA1 LPA
8 aortic atherosclerosis 9.9 APOE LPA
9 xanthoma disseminatum 9.8 APOB APOE
10 hypercholesterolemia, autosomal dominant, type b 9.8 APOB APOE
11 defective apolipoprotein b-100 9.8 APOB APOE
12 familial lcat deficiency 9.8 APOA1 APOA2 APOE
13 dysbaric osteonecrosis 9.8 APOA1 APOB
14 homozygous familial hypercholesterolemia 9.7 APOB APOE
15 vitamin e, familial isolated deficiency of 9.7 APOA1 APOB
16 amyloidosis, familial visceral 9.7 APOA1 APOA2 LPA
17 fetal macrosomia 9.7 APOA1 APOB
18 chylomicron retention disease 9.6 APOA1 APOB
19 schnyder corneal dystrophy 9.6 APOA2 APOB APOE
20 hypoalphalipoproteinemia, primary 9.5 APOA1 APOA2 APOB
21 hypobetalipoproteinemia, familial, 1 9.5 APOA1 APOB APOE
22 ischemic heart disease 9.5 APOA1 APOB APOE
23 hypertriglyceridemia, familial 9.5 APOA1 APOB APOE
24 hyperlipidemia, familial combined 9.5 APOA1 APOB APOE
25 coronary stenosis 9.5 APOA1 APOB APOE
26 abetalipoproteinemia 9.5 APOA1 APOB APOE
27 gallbladder disease 9.5 APOA1 APOB APOE
28 cerebrovascular disease 9.4 APOA1 APOB APOE
29 xanthomatosis 9.4 APOB APOE LPA
30 peripheral vascular disease 9.4 APOA1 APOB LPA
31 inherited metabolic disorder 9.4 APOA1 APOB
32 stroke, ischemic 9.3 APOB APOE LPA
33 diabetes mellitus, insulin-dependent 9.3 APOA1 APOB LPA
34 hyperlipoproteinemia, type iv 9.2 APOA1 APOA2 APOB APOE
35 hyperalphalipoproteinemia 1 9.2 APOA1 APOA2 APOB APOE
36 hypertension, essential 9.1 APOA1 APOB LPA
37 lipoprotein glomerulopathy 9.1 APOA2 APOB APOE LPA
38 hyperlipoproteinemia, type iii 9.1 APOA1 APOB APOE LPA
39 carotid artery disease 9.1 APOA1 APOB APOE LPA
40 familial hyperlipidemia 9.1 APOA1 APOB APOE LPA
41 lipid metabolism disorder 9.1 APOA1 APOB APOE LPA
42 arteries, anomalies of 9.1 APOA1 APOB APOE LPA
43 atherosclerosis susceptibility 9.1 APOA1 APOB APOE LPA
44 arteriosclerosis 9.0 APOA1 APOB APOE LPA
45 vascular disease 9.0 APOA1 APOB APOE LPA
46 hypolipoproteinemia 8.7 APOA1 APOA2 APOB APOE LPA
47 arcus corneae 8.7 APOA1 APOA2 APOB APOE LPA
48 lecithin:cholesterol acyltransferase deficiency 8.7 APOA1 APOA2 APOB APOE LPA
49 coronary heart disease 1 8.7 APOA1 APOA2 APOB APOE LPA
50 tangier disease 8.7 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:

53
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:

31 (show all 20)
# Description HPO Frequency HPO Source Accession
1 seizures 31 frequent (33%) HP:0001250
2 abnormal pyramidal signs 31 HP:0007256
3 failure to thrive 31 HP:0001508
4 eeg abnormality 31 HP:0002353
5 coarse facial features 31 HP:0000280
6 global developmental delay 31 HP:0001263
7 microcephaly 31 HP:0000252
8 visual impairment 31 HP:0000505
9 arthrogryposis multiplex congenita 31 HP:0002804
10 premature birth 31 HP:0001622
11 kyphoscoliosis 31 HP:0002751
12 leukodystrophy 31 HP:0002415
13 progressive flexion contractures 31 HP:0005876
14 spastic paraparesis 31 HP:0002313
15 muscular hypotonia of the trunk 31 HP:0008936
16 global brain atrophy 31 HP:0002283
17 corpus callosum atrophy 31 HP:0007371
18 projectile vomiting 31 HP:0002587
19 sudanophilic leukodystrophy 31 HP:0003269
20 diffuse cerebral sclerosis 31 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:

25
# 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 28 AIMP1

Anatomical Context for Leukodystrophy, Hypomyelinating, 3

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

38
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.115C> T (p.Gln39Ter) single nucleotide variant Pathogenic rs724159969 GRCh37 Chromosome 4, 107248613: 107248613
3 AIMP1 NM_001142415.1(AIMP1): c.334C> T (p.Gln112Ter) single nucleotide variant Pathogenic rs879253867 GRCh37 Chromosome 4, 107249343: 107249343

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 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 43)
# 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 9.9 APOA1 APOA2 APOB APOE
4 receptor-mediated endocytosis GO:0006898 9.84 APOA1 APOB APOE
5 cholesterol metabolic process GO:0008203 9.84 APOA1 APOA2 APOB APOE
6 steroid metabolic process GO:0008202 9.83 APOA1 APOB APOE
7 cholesterol homeostasis GO:0042632 9.8 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 high-density lipoprotein particle assembly GO:0034380 9.7 APOA1 APOA2 APOE
15 response to estrogen GO:0043627 9.69 APOA1 APOA2
16 phospholipid efflux GO:0033700 9.69 APOA1 APOA2 APOE
17 animal organ regeneration GO:0031100 9.68 APOA1 APOA2
18 tRNA aminoacylation for protein translation GO:0006418 9.68 AIMP1 AIMP2
19 triglyceride metabolic process GO:0006641 9.68 APOA2 APOE
20 negative regulation of endothelial cell proliferation GO:0001937 9.68 AIMP1 APOE
21 phosphatidylcholine biosynthetic process GO:0006656 9.67 APOA1 APOA2
22 triglyceride homeostasis GO:0070328 9.67 APOA1 APOE
23 artery morphogenesis GO:0048844 9.66 APOB APOE
24 chylomicron remnant clearance GO:0034382 9.65 APOB APOE
25 neuron projection regeneration GO:0031102 9.64 APOA1 APOE
26 regulation of Cdc42 protein signal transduction GO:0032489 9.64 APOA1 APOE
27 negative regulation of cytokine secretion involved in immune response GO:0002740 9.63 APOA1 APOA2
28 peptidyl-methionine modification GO:0018206 9.63 APOA1 APOA2
29 positive regulation of cholesterol esterification GO:0010873 9.63 APOA1 APOA2 APOE
30 very-low-density lipoprotein particle clearance GO:0034447 9.62 APOB APOE
31 regulation of intestinal cholesterol absorption GO:0030300 9.62 APOA1 APOA2
32 lipoprotein metabolic process GO:0042157 9.62 APOA1 APOA2 APOB APOE
33 negative regulation of lipase activity GO:0060192 9.61 APOA1 APOA2
34 lipoprotein catabolic process GO:0042159 9.61 APOB APOE
35 high-density lipoprotein particle clearance GO:0034384 9.61 APOA1 APOA2 APOE
36 protein oxidation GO:0018158 9.59 APOA1 APOA2
37 negative regulation of very-low-density lipoprotein particle remodeling GO:0010903 9.58 APOA1 APOA2
38 lipoprotein biosynthetic process GO:0042158 9.58 APOA1 APOB APOE
39 cholesterol efflux GO:0033344 9.56 APOA1 APOA2 APOB APOE
40 low-density lipoprotein particle remodeling GO:0034374 9.46 APOA2 APOB APOE LPA
41 chylomicron assembly GO:0034378 9.26 APOA1 APOA2 APOB APOE
42 chylomicron remodeling GO:0034371 8.92 APOA1 APOA2 APOB APOE
43 transport GO:0006810 10.09 APOA1 APOA2 APOB APOE LPA

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

(show all 16)
# 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 amyloid-beta binding GO:0001540 9.56 APOA1 APOE
4 phospholipid binding GO:0005543 9.56 APOA1 APOA2 APOB APOE
5 heat shock protein binding GO:0031072 9.55 APOA1 APOA2
6 phosphatidylcholine binding GO:0031210 9.54 APOA1 APOA2
7 low-density lipoprotein particle receptor binding GO:0050750 9.52 APOB APOE
8 cholesterol binding GO:0015485 9.5 APOA1 APOA2 APOE
9 high-density lipoprotein particle binding GO:0008035 9.49 APOA1 APOA2
10 lipase inhibitor activity GO:0055102 9.48 APOA1 APOA2
11 lipoprotein particle binding GO:0071813 9.46 APOA1 APOE
12 high-density lipoprotein particle receptor binding GO:0070653 9.4 APOA1 APOA2
13 apolipoprotein receptor binding GO:0034190 9.37 APOA1 APOA2
14 phosphatidylcholine-sterol O-acyltransferase activator activity GO:0060228 9.33 APOA1 APOA2 APOE
15 lipid transporter activity GO:0005319 9.26 APOA1 APOA2 APOB APOE
16 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
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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