HLD9
MCID: LKD016
MIFTS: 26

Leukodystrophy, Hypomyelinating, 9 (HLD9)

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

Aliases & Classifications for Leukodystrophy, Hypomyelinating, 9

MalaCards integrated aliases for Leukodystrophy, Hypomyelinating, 9:

Name: Leukodystrophy, Hypomyelinating, 9 57 74 29 6 72
Hld9 57 12 74
Rars-Related Autosomal Recessive Hypomyelinating Leukodystrophy 12 59
Leukodystrophy, Hypomyelinating, Type 9 40
Hypomyelinating Leukodystrophy 9 12

Characteristics:

Orphanet epidemiological data:

59
rars-related autosomal recessive hypomyelinating leukodystrophy
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
onset in the first year of life
six patients from 5 families have been reported (last curated november 2018)


HPO:

32
leukodystrophy, hypomyelinating, 9:
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity


Classifications:

Orphanet: 59  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0060791
MeSH 44 D020279
ICD10 33 E75.2
ICD10 via Orphanet 34 E75.2
Orphanet 59 ORPHA438114
UMLS 72 C4015323

Summaries for Leukodystrophy, Hypomyelinating, 9

OMIM : 57 Hypomyelinating leukodystrophy-9 is an autosomal recessive neurologic disorder characterized by onset of delayed psychomotor development, spasticity, and nystagmus in the first year of life. Additional neurologic features such as ataxia and abnormal movements may also occur. Brain imaging shows diffuse hypomyelination affecting all regions of the brain (summary by Wolf et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of HLD, see 312080. (616140)

MalaCards based summary : Leukodystrophy, Hypomyelinating, 9, is also known as hld9, and has symptoms including ataxia and action tremor. An important gene associated with Leukodystrophy, Hypomyelinating, 9 is RARS1 (Arginyl-TRNA Synthetase 1). Affiliated tissues include brain and eye, and related phenotypes are nystagmus and hyperreflexia

Disease Ontology : 12 A hypomyelinating leukodystrophy characterized by delayed psychomotor development, spasticity, and nystagmus starting in the first year of life that has material basis in compound heterozygous mutation in the RARS gene on chromosome 5q34.

UniProtKB/Swiss-Prot : 74 Leukodystrophy, hypomyelinating, 9: An autosomal recessive neurodegenerative disorder characterized by delayed psychomotor development, severe spasticity, nystagmus, and ataxia associated with diffuse hypomyelination apparent on brain MRI.

Related Diseases for Leukodystrophy, Hypomyelinating, 9

Symptoms & Phenotypes for Leukodystrophy, Hypomyelinating, 9

Human phenotypes related to Leukodystrophy, Hypomyelinating, 9:

59 32 (show all 31)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 nystagmus 59 32 frequent (33%) Frequent (79-30%) HP:0000639
2 hyperreflexia 59 32 frequent (33%) Frequent (79-30%) HP:0001347
3 global developmental delay 59 32 frequent (33%) Frequent (79-30%) HP:0001263
4 intellectual disability, mild 59 32 frequent (33%) Frequent (79-30%) HP:0001256
5 developmental stagnation 59 32 frequent (33%) Frequent (79-30%) HP:0007281
6 dysmetria 59 32 frequent (33%) Frequent (79-30%) HP:0001310
7 intention tremor 59 32 frequent (33%) Frequent (79-30%) HP:0002080
8 dystonia 59 32 frequent (33%) Frequent (79-30%) HP:0001332
9 difficulty walking 59 32 frequent (33%) Frequent (79-30%) HP:0002355
10 hyperintensity of cerebral white matter on mri 59 32 frequent (33%) Frequent (79-30%) HP:0030890
11 lower limb spasticity 59 32 frequent (33%) Frequent (79-30%) HP:0002061
12 hypoplasia of the corpus callosum 59 32 frequent (33%) Frequent (79-30%) HP:0002079
13 lower limb hypertonia 59 32 frequent (33%) Frequent (79-30%) HP:0006895
14 poor eye contact 59 32 frequent (33%) Frequent (79-30%) HP:0000817
15 poor head control 59 32 frequent (33%) Frequent (79-30%) HP:0002421
16 progressive extrapyramidal movement disorder 59 32 frequent (33%) Frequent (79-30%) HP:0007153
17 infantile axial hypotonia 59 32 frequent (33%) Frequent (79-30%) HP:0009062
18 cerebral hypomyelination 59 32 frequent (33%) Frequent (79-30%) HP:0006808
19 microcephaly 59 32 occasional (7.5%) Occasional (29-5%) HP:0000252
20 vomiting 59 32 occasional (7.5%) Occasional (29-5%) HP:0002013
21 increased serum lactate 59 32 occasional (7.5%) Occasional (29-5%) HP:0002151
22 focal-onset seizure 59 32 occasional (7.5%) Occasional (29-5%) HP:0007359
23 diffuse cerebral atrophy 59 32 occasional (7.5%) Occasional (29-5%) HP:0002506
24 pseudobulbar paralysis 59 32 occasional (7.5%) Occasional (29-5%) HP:0007024
25 absent smooth pursuit 59 32 occasional (7.5%) Occasional (29-5%) HP:0007179
26 dysarthria 59 32 Frequent (79-30%) HP:0001260
27 intellectual disability 32 HP:0001249
28 ataxia 59 Frequent (79-30%)
29 spasticity 32 HP:0001257
30 abnormality of extrapyramidal motor function 32 HP:0002071
31 leukodystrophy 32 HP:0002415

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
nystagmus
poor smooth pursuit
poor visual fixation (1 patient)

Head And Neck Head:
microcephaly (1 patient)

Neurologic Central Nervous System:
ataxia
dysarthria
hyperreflexia
dysmetria
intention tremor
more
Muscle Soft Tissue:
hypertonicity of the lower limbs

Clinical features from OMIM:

616140

UMLS symptoms related to Leukodystrophy, Hypomyelinating, 9:


ataxia, action tremor

Drugs & Therapeutics for Leukodystrophy, Hypomyelinating, 9

Search Clinical Trials , NIH Clinical Center for Leukodystrophy, Hypomyelinating, 9

Genetic Tests for Leukodystrophy, Hypomyelinating, 9

Genetic tests related to Leukodystrophy, Hypomyelinating, 9:

# Genetic test Affiliating Genes
1 Leukodystrophy, Hypomyelinating, 9 29 RARS1

Anatomical Context for Leukodystrophy, Hypomyelinating, 9

MalaCards organs/tissues related to Leukodystrophy, Hypomyelinating, 9:

41
Brain, Eye

Publications for Leukodystrophy, Hypomyelinating, 9

Articles related to Leukodystrophy, Hypomyelinating, 9:

# Title Authors PMID Year
1
Mutations in RARS cause a hypomyelination disorder akin to Pelizaeus-Merzbacher disease. 8 71
28905880 2017
2
Mutations in RARS cause hypomyelination. 8 71
24777941 2014

Variations for Leukodystrophy, Hypomyelinating, 9

ClinVar genetic disease variations for Leukodystrophy, Hypomyelinating, 9:

6
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 RARS1 NM_002887.4(RARS1): c.1846_1847del (p.Tyr616fs) deletion Pathogenic rs1064792894 5:167945040-167945041 5:168518035-168518036
2 RARS1 NM_002887.4(RARS1): c.2T> C (p.Met1Thr) single nucleotide variant Pathogenic rs769713780 5:167913505-167913505 5:168486500-168486500
3 RARS1 NM_002887.4(RARS1): c.5A> G (p.Asp2Gly) single nucleotide variant Pathogenic rs672601372 5:167913508-167913508 5:168486503-168486503
4 RARS1 NM_002887.4(RARS1): c.45+1G> T single nucleotide variant Pathogenic rs672601373 5:167913549-167913549 5:168486544-168486544
5 RARS1 NM_002887.4(RARS1): c.94_95TG[1] (p.Cys32fs) short repeat Pathogenic rs672601374 5:167915657-167915658 5:168488652-168488653
6 RARS1 NM_002887.4(RARS1): c.1A> G (p.Met1Val) single nucleotide variant Pathogenic rs672601375 5:167913504-167913504 5:168486499-168486499
7 RARS1 NM_002887.4(RARS1): c.1535G> A (p.Arg512Gln) single nucleotide variant Pathogenic rs369398935 5:167943865-167943865 5:168516860-168516860
8 RARS1 NM_002887.4(RARS1): c.1367C> T (p.Ser456Leu) single nucleotide variant Pathogenic rs139644798 5:167937606-167937606 5:168510601-168510601

UniProtKB/Swiss-Prot genetic disease variations for Leukodystrophy, Hypomyelinating, 9:

74
# Symbol AA change Variation ID SNP ID
1 RARS1 p.Asp2Gly VAR_072666 rs672601372
2 RARS1 p.Arg512Gln VAR_072667 rs369398935

Expression for Leukodystrophy, Hypomyelinating, 9

Search GEO for disease gene expression data for Leukodystrophy, Hypomyelinating, 9.

Pathways for Leukodystrophy, Hypomyelinating, 9

GO Terms for Leukodystrophy, Hypomyelinating, 9

Sources for Leukodystrophy, Hypomyelinating, 9

3 CDC
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64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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