HLD13
MCID: LKD022
MIFTS: 38

Leukodystrophy, Hypomyelinating, 13 (HLD13)

Categories: Ear diseases, Eye diseases, Fetal diseases, Genetic diseases, Mental diseases, Muscle diseases, Neuronal diseases, Rare diseases
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Aliases & Classifications for Leukodystrophy, Hypomyelinating, 13

MalaCards integrated aliases for Leukodystrophy, Hypomyelinating, 13:

Name: Leukodystrophy, Hypomyelinating, 13 57 73 38
Hypomyelinating Leukodystrophy 13 11 28 5 14
Hld13 57 11 73
C11orf73-Related Autosomal Recessive Hypomyelinating Leukoencephalopathy 58
C11orf73-Related Autosomal Recessive Hypomyelinating Leukodystrophy 58
Hypomyelinating Leukodystrophy Due to Hikeshi Deficiency 58

Characteristics:


Inheritance:

Autosomal recessive 57

Prevelance:

C11orf73-Related Autosomal Recessive Hypomyelinating Leukodystrophy: <1/1000000 (Worldwide) 58

Age Of Onset:

C11orf73-Related Autosomal Recessive Hypomyelinating Leukodystrophy: Infancy 58

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
onset in infancy
sudden death may occur
three families of ashkenazi jewish descent have been reported (last curated march 2016)


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases


Summaries for Leukodystrophy, Hypomyelinating, 13

OMIM®: 57 Hypomyelinating leukodystrophy-13 is an autosomal recessive neurodegenerative disorder characterized by infantile onset of delayed psychomotor development, axial hypotonia, and spasticity associated with delayed myelination and periventricular white matter abnormalities on brain imaging. More variable neurologic deficits, such as visual impairment, may also occur. Some patients may experience cardiac failure during acute illness (summary by Edvardson et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of HLD, see 312080. (616881) (Updated 08-Dec-2022)

MalaCards based summary: Leukodystrophy, Hypomyelinating, 13, also known as hypomyelinating leukodystrophy 13, is related to spastic ataxia 4 and leukodystrophy, hypomyelinating, 11. An important gene associated with Leukodystrophy, Hypomyelinating, 13 is HIKESHI (Heat Shock Protein Nuclear Import Factor Hikeshi), and among its related pathways/superpathways are Beta-Adrenergic Signaling and NFAT and Cardiac Hypertrophy. Affiliated tissues include brain, eye and heart, and related phenotypes are ataxia and visual impairment

Disease Ontology: 11 A hypomyelinating leukodystrophy characterized by autosomal recessive inheritance of infantile onset of delayed psychomotor development, axial hypotonia, and spasticity associated with delayed myelination and periventricular white matter abnormalities that has material basis in homozygous mutation in the C11ORF73 gene on chromosome 11q14.

UniProtKB/Swiss-Prot: 73 An autosomal recessive neurodegenerative disorder with infantile onset, affecting mainly the central white matter. Clinical features include early feeding difficulties, global developmental delay, postnatal progressive microcephaly, truncal hypotonia, spasticity, and variable neurologic deficits, such as visual impairment.

Orphanet: 58 A rare leukodystrophy characterized by infantile onset of lower limb spasticity and severe developmental delay associated with delayed myelination and periventricular white matter abnormalities. Other reported signs and symptoms include microcephaly, optic atrophy, nystagmus, ataxia, or seizures.

Related Diseases for Leukodystrophy, Hypomyelinating, 13

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
Leukodystrophy, Hypomyelinating, 18 Leukodystrophy, Hypomyelinating, 19, Transient Infantile
Leukodystrophy, Hypomyelinating, 20 Leukodystrophy, Hypomyelinating, 21
Leukodystrophy, Hypomyelinating, 22 Leukodystrophy, Hypomyelinating, 24

Diseases related to Leukodystrophy, Hypomyelinating, 13 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 22)
# Related Disease Score Top Affiliating Genes
1 spastic ataxia 4 9.9 POLR3B EIF2B2
2 leukodystrophy, hypomyelinating, 11 9.8 POLR3B HIKESHI EIF2B3
3 glycogen storage disease xv 9.8 EIF2B4 EIF2B3
4 leukoencephalopathy, hereditary diffuse, with spheroids 1 9.7 EIF2B4 EIF2B3
5 pelizaeus-merzbacher disease 9.7 POLR3B HYCC1 HIKESHI
6 childhood ataxia with central nervous system hypomyelination / vanishing white matter 9.6 EIF2B4 EIF2B3 EIF2B2
7 hemangioma of intra-abdominal structure 9.6 EIF2B4 EIF2B3 EIF2B2
8 combined saposin deficiency 9.6 EIF2B4 EIF2B3 EIF2B2
9 mehmo syndrome 9.6 EIF2B4 EIF2B3 EIF2B2
10 hypomyelinating leukoencephalopathy 9.5 POLR3B HYCC1 HIKESHI EIF2B2
11 leukodystrophy, hypomyelinating, 6 9.5 PYCR2 POLR3B
12 leukodystrophy, hypomyelinating, 4 9.5 PYCR2 HYCC1 HIKESHI
13 cerebral degeneration 9.4 POLR3B EIF2B4 EIF2B3 EIF2B2
14 leukoencephalopathy with vanishing white matter 9.4 POLR3B EIF2B4 EIF2B3 EIF2B2
15 hypomyelinating leukodystrophy 9.3 PYCR2 POLR3B HYCC1 HIKESHI
16 leukodystrophy, hypomyelinating, 9 9.3 POLR3B HYCC1 HIKESHI EIF2B4 EIF2B3
17 leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism 9.3 POLR3B HYCC1 HIKESHI EIF2B4 EIF2B3
18 peripheral demyelinating neuropathy, central dysmyelination, waardenburg syndrome, and hirschsprung disease 9.3 POLR3B HIKESHI EIF2B4 EIF2B3 EIF2B2
19 spastic ataxia 8 8.9 PYCR2 POLR3B HYCC1 HIKESHI EIF2B4 EIF2B3
20 leukodystrophy, hypomyelinating, 12 8.8 PYCR2 HYCC1 HIKESHI EIF2B4 EIF2B3 EIF2B2
21 leukodystrophy 8.6 PYCR2 POLR3B HYCC1 HIKESHI EIF2B4 EIF2B3
22 leukodystrophy, hypomyelinating, 10 8.6 PYCR2 POLR3B HYCC1 HIKESHI EIF2B4 EIF2B3

Graphical network of the top 20 diseases related to Leukodystrophy, Hypomyelinating, 13:



Diseases related to Leukodystrophy, Hypomyelinating, 13

Symptoms & Phenotypes for Leukodystrophy, Hypomyelinating, 13

Human phenotypes related to Leukodystrophy, Hypomyelinating, 13:

30 (show all 15)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ataxia 30 Occasional (7.5%) HP:0001251
2 visual impairment 30 Occasional (7.5%) HP:0000505
3 optic atrophy 30 Occasional (7.5%) HP:0000648
4 spasticity 30 HP:0001257
5 failure to thrive 30 HP:0001508
6 clonus 30 HP:0002169
7 nystagmus 30 HP:0000639
8 global developmental delay 30 HP:0001263
9 flexion contracture 30 HP:0001371
10 absent speech 30 HP:0001344
11 leukodystrophy 30 HP:0002415
12 feeding difficulties 30 HP:0011968
13 generalized hypotonia 30 HP:0001290
14 delayed myelination 30 HP:0012448
15 abnormal periventricular white matter morphology 30 HP:0002518

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Neurologic Central Nervous System:
spasticity
hyperreflexia
clonus
hypertonia
delayed myelination
more
Head And Neck Eyes:
nystagmus
optic atrophy (in some patients)
visual impairment (in some patients)

Abdomen Gastrointestinal:
feeding difficulties

Head And Neck Head:
small head circumference, progressive, postnatal (up to -2 sd)

Growth Other:
failure to thrive

Muscle Soft Tissue:
hypotonia

Skeletal:
joint contractures

Cardiovascular Heart:
heart failure, associated with febrile illness

Clinical features from OMIM®:

616881 (Updated 08-Dec-2022)

GenomeRNAi Phenotypes related to Leukodystrophy, Hypomyelinating, 13 according to GeneCards Suite gene sharing:

25 (show all 29)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased OCT4 protein expression GR00184-A-2 10.29 EIF2B2 EIF2B3 EIF2B4
2 Decreased OCT4 protein expression GR00184-A-5 10.29 EIF2B2 EIF2B3 EIF2B4
3 Decreased OCT4 protein expression GR00184-A-7 10.29 EIF2B2 EIF2B3 EIF2B4
4 Decreased NANOG protein expression GR00184-A-3 10.09 EIF2B2 EIF2B3 EIF2B4
5 Decreased NANOG protein expression GR00184-A-6 10.09 EIF2B2 EIF2B3 EIF2B4
6 Decreased NANOG protein expression GR00184-A-8 10.09 EIF2B2 EIF2B3 EIF2B4
7 Decreased POU5F1-GFP protein expression GR00184-A-1 10.03 EIF2B2 EIF2B3 EIF2B4
8 Decreased POU5F1-GFP protein expression GR00184-A-4 10.03 EIF2B2 EIF2B3 EIF2B4
9 Increased shRNA abundance (Z-score > 2) GR00366-A-104 9.68 EIF2B2
10 Increased shRNA abundance (Z-score > 2) GR00366-A-109 9.68 EIF2B2
11 Increased shRNA abundance (Z-score > 2) GR00366-A-111 9.68 PYCR2
12 Increased shRNA abundance (Z-score > 2) GR00366-A-116 9.68 EIF2B4 PYCR2
13 Increased shRNA abundance (Z-score > 2) GR00366-A-12 9.68 EIF2B2
14 Increased shRNA abundance (Z-score > 2) GR00366-A-120 9.68 EIF2B2
15 Increased shRNA abundance (Z-score > 2) GR00366-A-153 9.68 EIF2B4
16 Increased shRNA abundance (Z-score > 2) GR00366-A-178 9.68 EIF2B4
17 Increased shRNA abundance (Z-score > 2) GR00366-A-180 9.68 EIF2B4
18 Increased shRNA abundance (Z-score > 2) GR00366-A-197 9.68 POLR3B
19 Increased shRNA abundance (Z-score > 2) GR00366-A-20 9.68 EIF2B2
20 Increased shRNA abundance (Z-score > 2) GR00366-A-202 9.68 EIF2B2
21 Increased shRNA abundance (Z-score > 2) GR00366-A-216 9.68 POLR3B PYCR2
22 Increased shRNA abundance (Z-score > 2) GR00366-A-43 9.68 PYCR2
23 Increased shRNA abundance (Z-score > 2) GR00366-A-49 9.68 PYCR2
24 Increased shRNA abundance (Z-score > 2) GR00366-A-58 9.68 PYCR2
25 Increased shRNA abundance (Z-score > 2) GR00366-A-62 9.68 PYCR2
26 Increased shRNA abundance (Z-score > 2) GR00366-A-69 9.68 EIF2B2
27 Increased shRNA abundance (Z-score > 2) GR00366-A-76 9.68 EIF2B2
28 Increased shRNA abundance (Z-score > 2) GR00366-A-81 9.68 EIF2B4
29 Increased shRNA abundance (Z-score > 2) GR00366-A-99 9.68 POLR3B

Drugs & Therapeutics for Leukodystrophy, Hypomyelinating, 13

Search Clinical Trials, NIH Clinical Center for Leukodystrophy, Hypomyelinating, 13

Genetic Tests for Leukodystrophy, Hypomyelinating, 13

Genetic tests related to Leukodystrophy, Hypomyelinating, 13:

# Genetic test Affiliating Genes
1 Hypomyelinating Leukodystrophy 13 28 HIKESHI

Anatomical Context for Leukodystrophy, Hypomyelinating, 13

Organs/tissues related to Leukodystrophy, Hypomyelinating, 13:

MalaCards : Brain, Eye, Heart
ODiseA: Peripheral Nerve, Brain

Publications for Leukodystrophy, Hypomyelinating, 13

Articles related to Leukodystrophy, Hypomyelinating, 13:

# Title Authors PMID Year
1
Leukoencephalopathy and early death associated with an Ashkenazi-Jewish founder mutation in the Hikeshi gene. 57 5
26545878 2016

Variations for Leukodystrophy, Hypomyelinating, 13

ClinVar genetic disease variations for Leukodystrophy, Hypomyelinating, 13:

5
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 HIKESHI NM_016401.4(HIKESHI):c.160G>C (p.Val54Leu) SNV Pathogenic
224891 rs202003795 GRCh37: 11:86017416-86017416
GRCh38: 11:86306374-86306374
2 HIKESHI NM_016401.4(HIKESHI):c.325G>C (p.Ala109Pro) SNV Uncertain Significance
1029600 rs201042989 GRCh37: 11:86048477-86048477
GRCh38: 11:86337435-86337435

UniProtKB/Swiss-Prot genetic disease variations for Leukodystrophy, Hypomyelinating, 13:

73
# Symbol AA change Variation ID SNP ID
1 HIKESHI p.Val54Leu VAR_076411 rs202003795

Expression for Leukodystrophy, Hypomyelinating, 13

Search GEO for disease gene expression data for Leukodystrophy, Hypomyelinating, 13.

Pathways for Leukodystrophy, Hypomyelinating, 13

Pathways related to Leukodystrophy, Hypomyelinating, 13 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.19 EIF2B4 EIF2B3 EIF2B2
2
Show member pathways
12.07 EIF2B4 EIF2B3 EIF2B2
3
Show member pathways
11.78 EIF2B4 EIF2B3 EIF2B2
4
Show member pathways
10.67 EIF2B4 EIF2B3 EIF2B2

GO Terms for Leukodystrophy, Hypomyelinating, 13

Cellular components related to Leukodystrophy, Hypomyelinating, 13 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 eukaryotic translation initiation factor 2B complex GO:0005851 9.1 EIF2B4 EIF2B3 EIF2B2

Biological processes related to Leukodystrophy, Hypomyelinating, 13 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 T cell receptor signaling pathway GO:0050852 9.91 EIF2B4 EIF2B3 EIF2B2
2 response to glucose GO:0009749 9.88 EIF2B4 EIF2B3 EIF2B2
3 translational initiation GO:0006413 9.85 EIF2B4 EIF2B3 EIF2B2
4 myelination GO:0042552 9.8 EIF2B2 EIF2B4 HYCC1
5 ovarian follicle development GO:0001541 9.76 EIF2B4 EIF2B2
6 response to peptide hormone GO:0043434 9.73 EIF2B4 EIF2B3 EIF2B2
7 translation GO:0006412 9.65 EIF2B4 EIF2B3 EIF2B2
8 response to heat GO:0009408 9.63 EIF2B4 EIF2B3 EIF2B2
9 oligodendrocyte development GO:0014003 9.1 EIF2B4 EIF2B3 EIF2B2
10 cellular metabolic process GO:0044237 8.96 EIF2B4 EIF2B2

Molecular functions related to Leukodystrophy, Hypomyelinating, 13 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 guanyl-nucleotide exchange factor activity GO:0005085 9.43 EIF2B4 EIF2B3 EIF2B2
2 nucleotidyltransferase activity GO:0016779 9.33 POLR3B EIF2B3
3 translation initiation factor activity GO:0003743 9.1 EIF2B4 EIF2B3 EIF2B2

Sources for Leukodystrophy, Hypomyelinating, 13

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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