HMNDYT2
MCID: HYP713
MIFTS: 23

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 58 76 30 6
Hmndyt2 58 76
Dystonia-Parkinsonism-Hypermanganesemia Syndrome 60

Characteristics:

OMIM:

58
Inheritance:
autosomal recessive

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


HPO:

33
hypermanganesemia with dystonia 2:
Onset and clinical course progressive
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Hypermanganesemia with Dystonia 2

OMIM : 58 Hypermanganesemia with dystonia-2 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)

MalaCards based summary : Hypermanganesemia with Dystonia 2, also known as hmndyt2, is related to hypermanganesemia with dystonia. An important gene associated with Hypermanganesemia with Dystonia 2 is SLC39A14 (Solute Carrier Family 39 Member 14). Affiliated tissues include brain and liver, and related phenotypes are global developmental delay and cerebellar atrophy

UniProtKB/Swiss-Prot : 76 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

Diseases in the Hypermanganesemia with Dystonia family:

Hypermanganesemia with Dystonia 1 Hypermanganesemia with Dystonia 2

Diseases related to Hypermanganesemia with Dystonia 2 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 hypermanganesemia with dystonia 11.3

Symptoms & Phenotypes for Hypermanganesemia with Dystonia 2

Human phenotypes related to Hypermanganesemia with Dystonia 2:

60 33 (show all 30)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 global developmental delay 60 33 occasional (7.5%) Frequent (79-30%) HP:0001263
2 cerebellar atrophy 60 33 occasional (7.5%) Frequent (79-30%) HP:0001272
3 cerebral atrophy 60 33 occasional (7.5%) Frequent (79-30%) HP:0002059
4 postnatal microcephaly 33 occasional (7.5%) HP:0005484
5 intellectual disability 60 33 Frequent (79-30%) HP:0001249
6 spasticity 60 33 Frequent (79-30%) HP:0001257
7 tremor 60 33 Frequent (79-30%) HP:0001337
8 developmental regression 60 33 Frequent (79-30%) HP:0002376
9 scoliosis 60 33 Frequent (79-30%) HP:0002650
10 babinski sign 60 33 Frequent (79-30%) HP:0003487
11 oromandibular dystonia 60 33 Frequent (79-30%) HP:0012048
12 bradykinesia 60 33 Frequent (79-30%) HP:0002067
13 ankle clonus 60 33 Frequent (79-30%) HP:0011448
14 parkinsonism 60 33 Frequent (79-30%) HP:0001300
15 gait disturbance 33 HP:0001288
16 hyperreflexia 60 Frequent (79-30%)
17 dyskinesia 60 Frequent (79-30%)
18 flexion contracture 33 HP:0001371
19 dystonia 60 Frequent (79-30%)
20 multiple joint contractures 60 Frequent (79-30%)
21 bulbar signs 60 Frequent (79-30%)
22 hyperintensity of cerebral white matter on mri 60 Frequent (79-30%)
23 hypomimic face 60 Frequent (79-30%)
24 muscular hypotonia of the trunk 33 HP:0008936
25 poor speech 60 Frequent (79-30%)
26 progressive microcephaly 60 Frequent (79-30%)
27 infantile axial hypotonia 60 Frequent (79-30%)
28 progressive inability to walk 60 Frequent (79-30%)
29 scissor gait 60 Frequent (79-30%)
30 hypermanganesemia 60 Frequent (79-30%)

Symptoms via clinical synopsis from OMIM:

58
Neurologic Central Nervous System:
spasticity
tremor
hyperreflexia
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

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 30 SLC39A14

Anatomical Context for Hypermanganesemia with Dystonia 2

MalaCards organs/tissues related to Hypermanganesemia with Dystonia 2:

42
Brain, Liver

Publications for Hypermanganesemia with Dystonia 2

Variations for Hypermanganesemia with Dystonia 2

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

76
# 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

ClinVar genetic disease variations for Hypermanganesemia with Dystonia 2:

6 (show all 16)
# Gene Variation Type Significance SNP ID Assembly Location
1 SLC39A14 NM_015359.5(SLC39A14): c.292T> G (p.Phe98Val) single nucleotide variant Pathogenic rs879253763 GRCh38 Chromosome 8, 22408331: 22408331
2 SLC39A14 NM_015359.5(SLC39A14): c.292T> G (p.Phe98Val) single nucleotide variant Pathogenic rs879253763 GRCh37 Chromosome 8, 22265844: 22265844
3 SLC39A14 NM_015359.5(SLC39A14): c.313G> T (p.Glu105Ter) single nucleotide variant Pathogenic rs879253764 GRCh37 Chromosome 8, 22265865: 22265865
4 SLC39A14 NM_015359.5(SLC39A14): c.313G> T (p.Glu105Ter) single nucleotide variant Pathogenic rs879253764 GRCh38 Chromosome 8, 22408352: 22408352
5 SLC39A14 NM_015359.5(SLC39A14): c.477_478del (p.Ser160Cysfs) deletion Pathogenic rs879253765 GRCh38 Chromosome 8, 22409965: 22409966
6 SLC39A14 NM_015359.5(SLC39A14): c.477_478del (p.Ser160Cysfs) deletion Pathogenic rs879253765 GRCh37 Chromosome 8, 22267478: 22267479
7 SLC39A14 NM_015359.4(SLC39A14): c.1147G> A (p.Gly383Arg) single nucleotide variant Pathogenic rs879253766 GRCh37 Chromosome 8, 22273793: 22273793
8 SLC39A14 NM_015359.4(SLC39A14): c.1147G> A (p.Gly383Arg) single nucleotide variant Pathogenic rs879253766 GRCh38 Chromosome 8, 22416280: 22416280
9 SLC39A14 NM_015359.5(SLC39A14): c.1407C> G (p.Asn469Lys) single nucleotide variant Pathogenic rs750281602 GRCh37 Chromosome 8, 22277139: 22277139
10 SLC39A14 NM_015359.5(SLC39A14): c.1407C> G (p.Asn469Lys) single nucleotide variant Pathogenic rs750281602 GRCh38 Chromosome 8, 22419626: 22419626
11 SLC39A14 NM_015359.5(SLC39A14): c.367C> T (p.Gln123Ter) single nucleotide variant Pathogenic rs1554519011 GRCh37 Chromosome 8, 22265919: 22265919
12 SLC39A14 NM_015359.5(SLC39A14): c.367C> T (p.Gln123Ter) single nucleotide variant Pathogenic rs1554519011 GRCh38 Chromosome 8, 22408406: 22408406
13 SLC39A14 NM_015359.5(SLC39A14): c.512G> A (p.Gly171Glu) single nucleotide variant Pathogenic rs1554519303 GRCh38 Chromosome 8, 22410000: 22410000
14 SLC39A14 NM_015359.5(SLC39A14): c.512G> A (p.Gly171Glu) single nucleotide variant Pathogenic rs1554519303 GRCh37 Chromosome 8, 22267513: 22267513
15 SLC39A14 NM_015359.5(SLC39A14): c.751-9C> G single nucleotide variant Pathogenic rs1039778197 GRCh37 Chromosome 8, 22273273: 22273273
16 SLC39A14 NM_015359.5(SLC39A14): c.751-9C> G single nucleotide variant Pathogenic rs1039778197 GRCh38 Chromosome 8, 22415760: 22415760

Expression for Hypermanganesemia with Dystonia 2

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

Pathways for Hypermanganesemia with Dystonia 2

GO Terms for Hypermanganesemia with Dystonia 2

Sources for Hypermanganesemia with Dystonia 2

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