HLD21
MCID: LKD034
MIFTS: 21

Leukodystrophy, Hypomyelinating, 21 (HLD21)

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, 21

MalaCards integrated aliases for Leukodystrophy, Hypomyelinating, 21:

Name: Leukodystrophy, Hypomyelinating, 21 57 73 28 5
Hld21 57 73

Characteristics:


Inheritance:

Autosomal recessive 57

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
onset in infancy
progressive disorder
two unrelated patients of algerian descent have been reported (last curated april 2021)


Classifications:



Summaries for Leukodystrophy, Hypomyelinating, 21

OMIM®: 57 Hypomyelinating leukodystrophy-21 (HLD21) is an autosomal recessive neurodegenerative disorder characterized by global developmental delay apparent from infancy with loss of motor, speech, and cognitive milestones in the first decades of life. Affected individuals show cerebellar and pyramidal signs, including nystagmus, ataxia, dystonia, and spasticity, resulting in the loss of ambulation. Other more variable features include feeding difficulties, poor overall growth with microcephaly, optic atrophy, and seizures. Brain imaging shows diffuse hypomyelination of the white matter and atrophy of the cerebellum and corpus callosum. The disorder is progressive and may lead to premature death (summary by Dorboz et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of HLD, see 312080. (619310) (Updated 08-Dec-2022)

MalaCards based summary: Leukodystrophy, Hypomyelinating, 21, is also known as hld21. An important gene associated with Leukodystrophy, Hypomyelinating, 21 is POLR3K (RNA Polymerase III Subunit K). Affiliated tissues include cerebellum and brain, and related phenotypes are failure to thrive and nystagmus

UniProtKB/Swiss-Prot: 73 An autosomal recessive neurodegenerative disorder characterized by global developmental delay, loss of motor, speech and cognitive milestones in the first decades of life, and diffuse hypomyelination of the white matter and atrophy of the cerebellum and corpus callosum observed on brain imaging. Clinical features include nystagmus, ataxia, dystonia, and spasticity. Other more variable features are feeding difficulties, poor overall growth with microcephaly, optic atrophy, and seizures.The disorder is progressive and may lead to premature death.

Symptoms & Phenotypes for Leukodystrophy, Hypomyelinating, 21

Human phenotypes related to Leukodystrophy, Hypomyelinating, 21:

30 (show all 22)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 failure to thrive 30 Very rare (1%) HP:0001508
2 nystagmus 30 Very rare (1%) HP:0000639
3 ataxia 30 Very rare (1%) HP:0001251
4 dyskinesia 30 Very rare (1%) HP:0100660
5 microcephaly 30 Very rare (1%) HP:0000252
6 optic atrophy 30 Very rare (1%) HP:0000648
7 feeding difficulties in infancy 30 Very rare (1%) HP:0008872
8 absent speech 30 Very rare (1%) HP:0001344
9 cryptorchidism 30 Very rare (1%) HP:0000028
10 growth delay 30 Very rare (1%) HP:0001510
11 hypodontia 30 Very rare (1%) HP:0000668
12 mental deterioration 30 Very rare (1%) HP:0001268
13 dystonia 30 Very rare (1%) HP:0001332
14 cerebellar atrophy 30 Very rare (1%) HP:0001272
15 coma 30 Very rare (1%) HP:0001259
16 athetosis 30 Very rare (1%) HP:0002305
17 tetraparesis 30 Very rare (1%) HP:0002273
18 ketosis 30 Very rare (1%) HP:0001946
19 corpus callosum atrophy 30 Very rare (1%) HP:0007371
20 delayed ability to sit 30 Very rare (1%) HP:0025336
21 motor regression 30 Very rare (1%) HP:0033044
22 hypogonadotropic hypogonadism 30 Very rare (1%) HP:0000044

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Neurologic Central Nervous System:
spasticity
ataxia
hypotonia
global developmental delay
dyskinesia
more
Head And Neck Eyes:
nystagmus
optic atrophy (1 patient)

Genitourinary External Genitalia Male:
cryptorchidism

Head And Neck Head:
microcephaly (-3 sd)

Endocrine Features:
hypogonadotrophic hypogonadism (1 patient)

Growth Other:
failure to thrive
poor overall growth

Metabolic Features:
hypoglycemia
ketosis
episodic decompensation associate with stress

Abdomen Gastrointestinal:
feeding difficulties
tube-feeding

Head And Neck Teeth:
hypodontia (1 patient)

Clinical features from OMIM®:

619310 (Updated 08-Dec-2022)

Drugs & Therapeutics for Leukodystrophy, Hypomyelinating, 21

Search Clinical Trials, NIH Clinical Center for Leukodystrophy, Hypomyelinating, 21

Genetic Tests for Leukodystrophy, Hypomyelinating, 21

Genetic tests related to Leukodystrophy, Hypomyelinating, 21:

# Genetic test Affiliating Genes
1 Leukodystrophy, Hypomyelinating, 21 28 POLR3K

Anatomical Context for Leukodystrophy, Hypomyelinating, 21

Organs/tissues related to Leukodystrophy, Hypomyelinating, 21:

MalaCards : Cerebellum, Brain

Publications for Leukodystrophy, Hypomyelinating, 21

Articles related to Leukodystrophy, Hypomyelinating, 21:

# Title Authors PMID Year
1
Mutation in POLR3K causes hypomyelinating leukodystrophy and abnormal ribosomal RNA regulation. 57 5
30584594 2018

Variations for Leukodystrophy, Hypomyelinating, 21

ClinVar genetic disease variations for Leukodystrophy, Hypomyelinating, 21:

5
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 POLR3K NM_016310.5(POLR3K):c.121C>T (p.Arg41Trp) SNV Pathogenic
1065610 GRCh37: 16:101636-101636
GRCh38: 16:51636-51636

UniProtKB/Swiss-Prot genetic disease variations for Leukodystrophy, Hypomyelinating, 21:

73
# Symbol AA change Variation ID SNP ID
1 POLR3K p.Arg41Trp VAR_085543 rs1432006875

Expression for Leukodystrophy, Hypomyelinating, 21

Search GEO for disease gene expression data for Leukodystrophy, Hypomyelinating, 21.

Pathways for Leukodystrophy, Hypomyelinating, 21

GO Terms for Leukodystrophy, Hypomyelinating, 21

Sources for Leukodystrophy, Hypomyelinating, 21

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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