HMNDYT2
MCID: HYP713
MIFTS: 35

Hypermanganesemia with Dystonia 2 (HMNDYT2)

Categories: Genetic diseases, Liver diseases, Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Hypermanganesemia with Dystonia 2

MalaCards integrated aliases for Hypermanganesemia with Dystonia 2:

Name: Hypermanganesemia with Dystonia 2 57 12 72 29 6 15
Hmndyt2 57 72
Dystonia-Parkinsonism-Hypermanganesemia Syndrome 58
Hypermanganesemia with Dystonia, Type 2 39

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
onset in infancy or first years of life
some patients may respond to early chelation therapy


HPO:

31
hypermanganesemia with dystonia 2:
Inheritance autosomal recessive inheritance
Onset and clinical course progressive


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for Hypermanganesemia with Dystonia 2

OMIM® : 57 Hypermanganesemia with dystonia-2 (HMNDYT2) is an autosomal recessive neurodegenerative disorder characterized predominantly by loss of motor milestones in the first years of life. Affected individuals then develop rapidly progressive abnormal movements, including dystonia, spasticity, bulbar dysfunction, and variable features of parkinsonism, causing loss of ambulation. Cognition may be impaired, but is better preserved than motor function. The disorder results from abnormal accumulation of manganese (Mn), which is toxic to neurons. Chelation therapy, if started early, may provide clinical benefit (summary by Tuschl et al., 2016). For a discussion of genetic heterogeneity of HMNDYT, see HMNDYT1 (613280). (617013) (Updated 20-May-2021)

MalaCards based summary : Hypermanganesemia with Dystonia 2, also known as hmndyt2, is related to hypermanganesemia with dystonia and ehlers-danlos syndrome, spondylodysplastic type, 3. An important gene associated with Hypermanganesemia with Dystonia 2 is SLC39A14 (Solute Carrier Family 39 Member 14), and among its related pathways/superpathways are NRF2 pathway and Metal ion SLC transporters. Affiliated tissues include liver and brain, and related phenotypes are intellectual disability and scoliosis

Disease Ontology : 12 A hypermanganesemia with dystonia that is characterized predominantly by loss of motor milestones in the first years of life and has material basis in homozygous mutation in the SLC39A14 gene on chromosome 8p21.

UniProtKB/Swiss-Prot : 72 Hypermanganesemia with dystonia 2: A metabolic autosomal recessive disorder characterized by increased blood manganese levels, neurodegeneration, and rapidly progressive parkinsonism and dystonia. Affected individuals present with loss of developmental milestones, progressive dystonia and bulbar dysfunction in infancy or early childhood. Towards the end of the first decade, they manifest severe generalized pharmacoresistant dystonia, spasticity, limb contractures and scoliosis, and loss of independent ambulation. Cognition may be impaired, but is better preserved than motor function.

Related Diseases for Hypermanganesemia with Dystonia 2

Graphical network of the top 20 diseases related to Hypermanganesemia with Dystonia 2:



Diseases related to Hypermanganesemia with Dystonia 2

Symptoms & Phenotypes for Hypermanganesemia with Dystonia 2

Human phenotypes related to Hypermanganesemia with Dystonia 2:

58 31 (show all 30)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 58 31 frequent (33%) Frequent (79-30%) HP:0001249
2 scoliosis 58 31 frequent (33%) Frequent (79-30%) HP:0002650
3 tremor 58 31 frequent (33%) Frequent (79-30%) HP:0001337
4 developmental regression 58 31 frequent (33%) Frequent (79-30%) HP:0002376
5 global developmental delay 58 31 occasional (7.5%) Frequent (79-30%) HP:0001263
6 dyskinesia 58 31 frequent (33%) Frequent (79-30%) HP:0100660
7 multiple joint contractures 58 31 frequent (33%) Frequent (79-30%) HP:0002828
8 bulbar signs 58 31 frequent (33%) Frequent (79-30%) HP:0002483
9 babinski sign 58 31 frequent (33%) Frequent (79-30%) HP:0003487
10 cerebellar atrophy 58 31 occasional (7.5%) Frequent (79-30%) HP:0001272
11 cerebral atrophy 58 31 occasional (7.5%) Frequent (79-30%) HP:0002059
12 progressive inability to walk 58 31 frequent (33%) Frequent (79-30%) HP:0002505
13 ankle clonus 58 31 frequent (33%) Frequent (79-30%) HP:0011448
14 poor speech 58 31 frequent (33%) Frequent (79-30%) HP:0002465
15 parkinsonism 58 31 frequent (33%) Frequent (79-30%) HP:0001300
16 bradykinesia 58 31 frequent (33%) Frequent (79-30%) HP:0002067
17 infantile axial hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0009062
18 hypomimic face 58 31 frequent (33%) Frequent (79-30%) HP:0000338
19 progressive microcephaly 58 31 frequent (33%) Frequent (79-30%) HP:0000253
20 hyperintensity of cerebral white matter on mri 58 31 frequent (33%) Frequent (79-30%) HP:0030890
21 oromandibular dystonia 58 31 frequent (33%) Frequent (79-30%) HP:0012048
22 scissor gait 58 31 frequent (33%) Frequent (79-30%) HP:0012407
23 hypermanganesemia 58 31 frequent (33%) Frequent (79-30%) HP:0032097
24 postnatal microcephaly 31 occasional (7.5%) HP:0005484
25 spasticity 58 31 Frequent (79-30%) HP:0001257
26 hyperreflexia 58 Frequent (79-30%)
27 gait disturbance 31 HP:0001288
28 flexion contracture 31 HP:0001371
29 dystonia 58 Frequent (79-30%)
30 muscular hypotonia of the trunk 31 HP:0008936

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
spasticity
hyperreflexia
tremor
developmental regression
dystonia
more
Head And Neck Mouth:
oromandibular dystonia
bulbar dysfunction

Muscle Soft Tissue:
axial hypotonia

Laboratory Abnormalities:
increased blood manganese

Skeletal Spine:
scoliosis

Skeletal:
joint contractures

Head And Neck Head:
microcephaly, acquired (in some patients)

Clinical features from OMIM®:

617013 (Updated 20-May-2021)

Drugs & Therapeutics for Hypermanganesemia with Dystonia 2

Search Clinical Trials , NIH Clinical Center for Hypermanganesemia with Dystonia 2

Genetic Tests for Hypermanganesemia with Dystonia 2

Genetic tests related to Hypermanganesemia with Dystonia 2:

# Genetic test Affiliating Genes
1 Hypermanganesemia with Dystonia 2 29 SLC39A14

Anatomical Context for Hypermanganesemia with Dystonia 2

MalaCards organs/tissues related to Hypermanganesemia with Dystonia 2:

40
Liver, Brain

Publications for Hypermanganesemia with Dystonia 2

Articles related to Hypermanganesemia with Dystonia 2:

# Title Authors PMID Year
1
Novel founder intronic variant in SLC39A14 in two families causing Manganism and potential treatment strategies. 6 57
29685658 2018
2
Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood-onset parkinsonism-dystonia. 57
27231142 2016

Variations for Hypermanganesemia with Dystonia 2

ClinVar genetic disease variations for Hypermanganesemia with Dystonia 2:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 SLC39A14 NM_001128431.4(SLC39A14):c.367C>T (p.Gln123Ter) SNV Pathogenic 446705 rs1554519011 GRCh37: 8:22265919-22265919
GRCh38: 8:22408406-22408406
2 SLC39A14 NM_001128431.4(SLC39A14):c.1407C>G (p.Asn469Lys) SNV Pathogenic 242928 rs750281602 GRCh37: 8:22277139-22277139
GRCh38: 8:22419626-22419626
3 SLC39A14 NM_001128431.4(SLC39A14):c.292T>G (p.Phe98Val) SNV Pathogenic 242924 rs879253763 GRCh37: 8:22265844-22265844
GRCh38: 8:22408331-22408331
4 SLC39A14 NM_001128431.4(SLC39A14):c.1147G>A (p.Gly383Arg) SNV Pathogenic 242927 rs879253766 GRCh37: 8:22273793-22273793
GRCh38: 8:22416280-22416280
5 SLC39A14 NM_001128431.4(SLC39A14):c.457+1504G>A SNV Pathogenic 446706 rs1554519303 GRCh37: 8:22267513-22267513
GRCh38: 8:22410000-22410000
6 SLC39A14 NM_001128431.4(SLC39A14):c.313G>T (p.Glu105Ter) SNV Pathogenic 242925 rs879253764 GRCh37: 8:22265865-22265865
GRCh38: 8:22408352-22408352
7 SLC39A14 NM_001128431.4(SLC39A14):c.457+1469_457+1470del Deletion Pathogenic 242926 rs879253765 GRCh37: 8:22267478-22267479
GRCh38: 8:22409965-22409966
8 SLC39A14 NM_001128431.4(SLC39A14):c.751-9C>G SNV Likely pathogenic 446707 rs1039778197 GRCh37: 8:22273273-22273273
GRCh38: 8:22415760-22415760

UniProtKB/Swiss-Prot genetic disease variations for Hypermanganesemia with Dystonia 2:

72
# Symbol AA change Variation ID SNP ID
1 SLC39A14 p.Phe98Val VAR_077004 rs879253763
2 SLC39A14 p.Gly383Arg VAR_077005 rs879253766
3 SLC39A14 p.Asn469Lys VAR_077006 rs750281602

Expression for Hypermanganesemia with Dystonia 2

Search GEO for disease gene expression data for Hypermanganesemia with Dystonia 2.

Pathways for Hypermanganesemia with Dystonia 2

Pathways related to Hypermanganesemia with Dystonia 2 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.12 SLC39A14 SLC39A13
2
Show member pathways
10.78 SLC39A14 SLC39A13 SLC30A9

GO Terms for Hypermanganesemia with Dystonia 2

Cellular components related to Hypermanganesemia with Dystonia 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 Golgi membrane GO:0000139 8.8 SLC39A13 SLC33A1 AP1S1

Biological processes related to Hypermanganesemia with Dystonia 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ion transport GO:0006811 9.56 SLC39A14 SLC39A13 SLC30A9 SLC25A28
2 transmembrane transport GO:0055085 9.46 SLC39A14 SLC39A13 SLC33A1 SLC30A9
3 metal ion transport GO:0030001 9.37 SLC39A14 SLC39A13
4 zinc ion transmembrane transport GO:0071577 9.32 SLC39A14 SLC39A13
5 cellular zinc ion homeostasis GO:0006882 9.13 SLC39A14 SLC39A13 SLC30A9
6 zinc ion transport GO:0006829 8.8 SLC39A14 SLC39A13 SLC30A9

Molecular functions related to Hypermanganesemia with Dystonia 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 zinc ion transmembrane transporter activity GO:0005385 9.16 SLC39A14 SLC39A13
2 metal ion transmembrane transporter activity GO:0046873 8.96 SLC39A14 SLC39A13
3 iron ion transmembrane transporter activity GO:0005381 8.62 SLC39A14 SLC25A28

Sources for Hypermanganesemia with Dystonia 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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