MCID: LKD015
MIFTS: 43

Leukodystrophy, Hypomyelinating, 3

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

Aliases & Classifications for Leukodystrophy, Hypomyelinating, 3

MalaCards integrated aliases for Leukodystrophy, Hypomyelinating, 3:

Name: Leukodystrophy, Hypomyelinating, 3 54 71 13
Leukodystrophy, Hypomyelinating 3 50 24 29
Hld3 12 24 71
Pelizaeus-Merzbacher-Like Disease Due to Aimp1 Mutation 12 56
Hypomyelinating Leukodystrophy 3 12 14
Pelizaeus-Merzbacher-Like Disease, Autosomal Recessive, 2 69
Perinatal Sudanophilic Leukodystrophy 50

Characteristics:

Orphanet epidemiological data:

56
pelizaeus-merzbacher-like disease due to aimp1 mutation
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal; Age of death: early childhood;

OMIM:

54
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: 56  
Rare neurological diseases


Summaries for Leukodystrophy, Hypomyelinating, 3

OMIM : 54
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 systemic lupus erythematosus with nephritis 1 and short stature, brachydactyly, intellectual developmental disability, and seizures, and has symptoms including failure to thrive, visual impairment and seizures. 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

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.

NIH Rare Diseases : 50 this condition doesn't have a summary yet. please see our page(s) on leukodystrophy.

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.

Related Diseases for Leukodystrophy, Hypomyelinating, 3

Diseases in the Hypomyelinating Leukodystrophy family:

Leukodystrophy, Hypomyelinating, 2 Leukodystrophy, Hypomyelinating, 10
Leukodystrophy, Hypomyelinating, 4 Leukodystrophy, Hypomyelinating, 3
Leukodystrophy, Hypomyelinating, 9 Leukodystrophy, Hypomyelinating, 11
Leukodystrophy, Hypomyelinating, 5 Leukodystrophy, Hypomyelinating, 13
Leukodystrophy, Hypomyelinating, 12 Leukodystrophy, Hypomyelinating, 6

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

(show top 50) (show all 56)
id Related Disease Score Top Affiliating Genes
1 systemic lupus erythematosus with nephritis 1 10.4 AIMP1 POLR3A
2 short stature, brachydactyly, intellectual developmental disability, and seizures 10.2 APOA1 APOA2
3 hereditary congenital facial paresis 10.2 APOA1 APOA2
4 pars planitis 10.2 APOA1 APOE
5 amelogenesis imperfecta, type iia3 10.1 APOA1 APOE
6 amyloidosis nodular localized cutaneous 10.0 APOA1 LPA
7 arthritis 9.9 APOE LPA
8 xk aprosencephaly 9.9 APOB APOE
9 hypercholesterolemia, due to ligand-defective apo b 9.9 APOB APOE
10 delta-1-pyrroline-5-carboxylate dehydrogenase deficiency 9.9 APOB APOE
11 cataract, autosomal dominant congenital 4 9.8 APOB APOE
12 otospondylomegaepiphyseal dysplasia 9.8 APOA1 APOB
13 familial osteochondritis dissecans 9.8 APOA1 APOA2 APOE
14 prieto syndrome 9.8 AIMP1 POLR3A
15 legg-calve-perthes disease 9.8 APOA1 APOB
16 infantile-onset mesial temporal lobe epilepsy with severe cognitive regression 9.7 APOB APOE
17 fetal parvovirus syndrome 9.7 APOA1 APOB
18 afibrinogenemia, congenital 9.6 APOA1 APOA2 LPA
19 carnitine deficiency, systemic primary 9.6 APOA1 APOB
20 joubert syndrome 21 9.6 APOA1 APOB
21 ovarian clear cell malignant adenofibroma 9.5 APOA1 APOB
22 hypobetalipoproteinemia 9.4 APOB APOE
23 islet cell tumor 9.4 APOA1 APOB APOE
24 pontocerebellar hypoplasia 9.4 APOA1 APOB APOE
25 melorheostosis 9.4 APOA1 APOB APOE
26 wolfram syndrome 2 9.4 APOA1 APOB APOE
27 malignant type ab thymoma 9.3 APOA1 APOB APOE
28 malignant fibrous histiocytoma of bone 9.3 APOB APOE LPA
29 dental anomalies and short stature 9.3 APOA1 APOB LPA
30 angina pectoris 9.3 APOA1 APOB LPA
31 stroke, ischemic 9.2 APOB APOE LPA
32 autoimmune hepatitis 9.1 APOB APOE LPA
33 hypertension, essential 9.1 APOA1 APOB LPA
34 hyperlipidemia, familial combined 9.0 APOA1 APOA2 APOB APOE
35 lissencephaly 6, with microcephaly 9.0 APOA1 APOA2 APOB APOE
36 hyperchylomicronemia, late-onset 8.9 APOA1 APOA2 APOB APOE
37 mental retardation, autosomal dominant 45 8.9 APOA2 APOB APOE LPA
38 alzheimer disease-2 8.8 APOA1 APOB APOE LPA
39 chondrocalcinosis with early-onset osteoarthritis 8.8 APOA1 APOB APOE LPA
40 glossopharyngeal nerve disease 8.8 APOA1 APOB APOE LPA
41 acute apical periodontitis 8.8 APOA1 APOB APOE LPA
42 skin squamous cell carcinoma 8.8 APOA1 APOB APOE LPA
43 myelophthisic anemia 8.8 APOA1 APOB APOE LPA
44 pericarditis 8.8 APOA1 APOB APOE LPA
45 bird fancier's lung 8.4 APOA1 APOA2 APOB APOE LPA
46 stone in bladder diverticulum 8.4 APOA1 APOA2 APOB APOE LPA
47 fish-eye disease 8.4 APOA1 APOA2 APOB APOE LPA
48 von hippel-lindau syndrome 8.4 APOA1 APOB APOE LPA
49 apolipoprotein c-iii deficiency 8.4 APOA1 APOA2 APOB APOE LPA
50 obesity, hyperphagia, and developmental delay 8.3 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:

54

Growth- Other:
failure to thrive

Neurologic- Central Nervous System:
abnormal eeg
pyramidal signs
axial hypotonia
spastic paraparesis
generalized brain atrophy
more
Skeletal- Spine:
kyphoscoliosis

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

Head And Neck- Face:
coarse facies

Head And Neck- Head:
microcephaly

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

id Genetic test Affiliating Genes
1 Leukodystrophy, Hypomyelinating 3 29 24 AIMP1

Anatomical Context for Leukodystrophy, Hypomyelinating, 3

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

39
Brain

Publications for Leukodystrophy, Hypomyelinating, 3

Variations for Leukodystrophy, Hypomyelinating, 3

ClinVar genetic disease variations for Leukodystrophy, Hypomyelinating, 3:

6
id 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)
id Super pathways Score Top Affiliating Genes
1
Show member pathways
13.54 AIMP1 APOA1 APOA2 APOB APOE LPA
2
Show member pathways
12.23 APOA1 APOA2 APOB APOE
3
Show member pathways
11.89 APOA1 APOA2 APOB APOE LPA
4
Show member pathways
11.79 APOA1 APOA2 APOB APOE
5
Show member pathways
11.45 APOA1 APOB APOE
6 11.37 APOA1 APOA2
7 11.18 APOB LPA
8
Show member pathways
11.12 APOA1 APOB
9 10.87 APOA1 APOA2
10 10.81 APOA1 APOB
11
Show member pathways
10.76 APOA1 APOA2 APOB APOE
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 15)
id Name GO ID Score Top Affiliating Genes
1 extracellular region GO:0005576 9.97 AIMP1 APOA1 APOA2 APOB APOE LPA
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 spherical high-density lipoprotein particle GO:0034366 9.48 APOA1 APOA2
11 low-density lipoprotein particle GO:0034362 9.43 APOA1 APOB APOE
12 intermediate-density lipoprotein particle GO:0034363 9.33 APOA1 APOB APOE
13 very-low-density lipoprotein particle GO:0034361 9.26 APOA1 APOA2 APOB APOE
14 discoidal high-density lipoprotein particle GO:0034365 9.1 APOA1
15 chylomicron GO:0042627 8.92 APOA1 APOA2 APOB APOE

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

(show all 42)
id 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 9.94 APOA1 APOA2 APOB APOE
3 cellular protein metabolic process GO:0044267 9.88 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 lipid transport GO:0006869 9.77 APOA1 APOA2 APOB APOE LPA
9 triglyceride catabolic process GO:0019433 9.75 APOA1 APOB APOE
10 cholesterol transport GO:0030301 9.74 APOA1 APOA2 APOB
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 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 triglyceride metabolic process GO:0006641 9.68 APOA2 APOE
19 negative regulation of endothelial cell proliferation GO:0001937 9.68 AIMP1 APOE
20 phosphatidylcholine biosynthetic process GO:0006656 9.67 APOA1 APOA2
21 triglyceride homeostasis GO:0070328 9.67 APOA1 APOE
22 artery morphogenesis GO:0048844 9.66 APOB APOE
23 chylomicron remnant clearance GO:0034382 9.65 APOB APOE
24 neuron projection regeneration GO:0031102 9.65 APOA1 APOE
25 positive regulation of cholesterol esterification GO:0010873 9.65 APOA1 APOA2 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 high-density lipoprotein particle clearance GO:0034384 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 cholesterol efflux GO:0033344 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 protein oxidation GO:0018158 9.6 APOA1 APOA2
36 negative regulation of very-low-density lipoprotein particle remodeling GO:0010903 9.59 APOA1 APOA2
37 lipoprotein biosynthetic process GO:0042158 9.58 APOA1 APOB APOE
38 lipoprotein metabolic process GO:0042157 9.56 APOA1 APOA2 APOB APOE
39 low-density lipoprotein particle remodeling GO:0034374 9.46 APOA2 APOB APOE LPA
40 chylomicron assembly GO:0034378 9.26 APOA1 APOA2 APOB APOE
41 chylomicron remodeling GO:0034371 8.92 APOA1 APOA2 APOB APOE
42 transport GO:0006810 10.08 APOA1 APOA2 APOB APOE LPA

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

(show all 16)
id 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 heat shock protein binding GO:0031072 9.56 APOA1 APOA2
4 phospholipid binding GO:0005543 9.56 APOA1 APOA2 APOB APOE
5 beta-amyloid binding GO:0001540 9.55 APOA1 APOE
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
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 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 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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