HMNDYT1
MCID: HYP716
MIFTS: 34

Hypermanganesemia with Dystonia 1 (HMNDYT1)

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

Aliases & Classifications for Hypermanganesemia with Dystonia 1

MalaCards integrated aliases for Hypermanganesemia with Dystonia 1:

Name: Hypermanganesemia with Dystonia 1 57 12 72
Hypermanganesemia with Dystonia, Polycythemia, and Cirrhosis 57 72 29 13 6
Hypermanganesemia with Dystonia Polycythemia and Cirrhosis 20 70
Hmndyt1 57 72
Hmdpc 57 72
Hypermanganesemia with Dystonia, Polycythemia, and Cirrhosis; Hmdpc 57
Hypermanganesemia with Dystonia, Polycythemia and Cirrhosis 39
Cirrhosis-Dystonia-Polycythemia-Hypermanganesemia Syndrome 58

Characteristics:

Orphanet epidemiological data:

58
cirrhosis-dystonia-polycythemia-hypermanganesemia syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood; Age of death: normal life expectancy;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
onset usually in first decade
adult onset of neurologic symptoms has been reported in 1 family
chelation therapy can result in clinical improvement


HPO:

31
hypermanganesemia with dystonia 1:
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare hepatic diseases
Inborn errors of metabolism


Summaries for Hypermanganesemia with Dystonia 1

OMIM® : 57 Hypermanganesemia with dystonia-1 (HMNDYT1) is an autosomal recessive metabolic disorder characterized by increased serum manganese, motor neurodegeneration with extrapyramidal features, polycythemia, and hepatic dysfunction, which leads to cirrhosis in some cases. Intellectual function is preserved (summary by Tuschl et al., 2012 and Quadri et al., 2012). (613280) (Updated 05-Apr-2021)

MalaCards based summary : Hypermanganesemia with Dystonia 1, also known as hypermanganesemia with dystonia, polycythemia, and cirrhosis, is related to hypermanganesemia with dystonia and hypermanganesemia with dystonia 2, and has symptoms including tremor, abnormality of extrapyramidal motor function and bradykinesia. An important gene associated with Hypermanganesemia with Dystonia 1 is SLC30A10 (Solute Carrier Family 30 Member 10). Affiliated tissues include liver, globus pallidus and brain, and related phenotypes are dysarthria and splenomegaly

Disease Ontology : 12 A hypermanganesemia with dystonia that is characterized by increased serum manganese, motor neurodegeneration with extrapyramidal features, polycythemia, and hepatic dysfunction and has material basis in homozygous mutation in the SLC30A10 gene on chromosome 1q41.

UniProtKB/Swiss-Prot : 72 Hypermanganesemia with dystonia 1: A metabolic autosomal recessive disorder characterized by dystonia, parkinsonism, extrapyramidal signs, severe hypermanganesemia, polycythemia, and chronic hepatic disease, including steatosis and cirrhosis.

Related Diseases for Hypermanganesemia with Dystonia 1

Diseases in the Hypermanganesemia with Dystonia family:

Hypermanganesemia with Dystonia 1 Hypermanganesemia with Dystonia 2

Diseases related to Hypermanganesemia with Dystonia 1 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 hypermanganesemia with dystonia 11.3
2 hypermanganesemia with dystonia 2 10.9
3 liver cirrhosis 10.4
4 polycythemia 10.4
5 dystonia/parkinsonism, hypermanganesemia, polycythemia, and chronic liver disease 10.4
6 dystonia 10.1

Graphical network of the top 20 diseases related to Hypermanganesemia with Dystonia 1:



Diseases related to Hypermanganesemia with Dystonia 1

Symptoms & Phenotypes for Hypermanganesemia with Dystonia 1

Human phenotypes related to Hypermanganesemia with Dystonia 1:

58 31 (show all 49)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 dysarthria 58 31 frequent (33%) Frequent (79-30%) HP:0001260
2 splenomegaly 58 31 frequent (33%) Frequent (79-30%) HP:0001744
3 hepatomegaly 58 31 frequent (33%) Frequent (79-30%) HP:0002240
4 portal hypertension 58 31 frequent (33%) Frequent (79-30%) HP:0001409
5 elevated hepatic transaminase 58 31 frequent (33%) Frequent (79-30%) HP:0002910
6 dystonia 58 31 frequent (33%) Frequent (79-30%) HP:0001332
7 dysdiadochokinesis 58 31 frequent (33%) Frequent (79-30%) HP:0002075
8 peripheral neuropathy 58 31 frequent (33%) Frequent (79-30%) HP:0009830
9 esophageal varix 58 31 frequent (33%) Frequent (79-30%) HP:0002040
10 polycythemia 58 31 frequent (33%) Frequent (79-30%) HP:0001901
11 rigidity 58 31 frequent (33%) Frequent (79-30%) HP:0002063
12 difficulty walking 58 31 frequent (33%) Frequent (79-30%) HP:0002355
13 postural instability 58 31 frequent (33%) Frequent (79-30%) HP:0002172
14 bradykinesia 58 31 frequent (33%) Frequent (79-30%) HP:0002067
15 abnormal basal ganglia mri signal intensity 58 31 frequent (33%) Frequent (79-30%) HP:0012751
16 abnormal myelination 58 31 frequent (33%) Frequent (79-30%) HP:0012447
17 hypomimic face 58 31 frequent (33%) Frequent (79-30%) HP:0000338
18 abnormal transferrin saturation 58 31 frequent (33%) Frequent (79-30%) HP:0040135
19 action tremor 58 31 frequent (33%) Frequent (79-30%) HP:0002345
20 abnormal globus pallidus morphology 58 31 frequent (33%) Frequent (79-30%) HP:0002453
21 micronodular cirrhosis 58 31 frequent (33%) Frequent (79-30%) HP:0001413
22 abnormal blood inorganic cation concentration 31 frequent (33%) HP:0010927
23 abnormality of amino acid metabolism 58 31 occasional (7.5%) Occasional (29-5%) HP:0004337
24 microcephaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0000252
25 hypertrophic cardiomyopathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0001639
26 jaundice 58 31 occasional (7.5%) Occasional (29-5%) HP:0000952
27 low levels of vitamin e 58 31 occasional (7.5%) Occasional (29-5%) HP:0100513
28 prolonged prothrombin time 58 31 occasional (7.5%) Occasional (29-5%) HP:0008151
29 spastic paraparesis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002313
30 poor fine motor coordination 58 31 occasional (7.5%) Occasional (29-5%) HP:0007010
31 truncal ataxia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002078
32 astrocytosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002446
33 increased total iron binding capacity 58 31 occasional (7.5%) Occasional (29-5%) HP:0025196
34 hyperglycinemia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002154
35 copper accumulation in liver 58 31 occasional (7.5%) Occasional (29-5%) HP:0025321
36 sensorimotor neuropathy 31 occasional (7.5%) HP:0007141
37 decreased circulating ferritin concentration 31 occasional (7.5%) HP:0012343
38 gait disturbance 58 Frequent (79-30%)
39 tremor 31 HP:0001337
40 hypertonia 58 Frequent (79-30%)
41 cirrhosis 31 HP:0001394
42 abnormality of coagulation 58 Occasional (29-5%)
43 abnormality of the liver 58 Frequent (79-30%)
44 hyperbilirubinemia 31 HP:0002904
45 steppage gait 31 HP:0003376
46 parkinsonism 31 HP:0001300
47 decreased liver function 31 HP:0001410
48 decreased serum ferritin 58 Occasional (29-5%)
49 abnormality of divalent inorganic cation homeostasis 58 Frequent (79-30%)

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
dysarthria
tremor
dystonia
rigidity
postural instability
more
Hematology:
polycythemia

Neurologic Peripheral Nervous System:
sensorimotor neuropathy (1 patient)

Abdomen Liver:
hepatomegaly
cirrhosis
liver dysfunction

Laboratory Abnormalities:
increased total iron binding capacity
increased liver enzymes
hyperbilirubinemia, unconjugated
increased serum manganese
increased erythropoietin
more

Clinical features from OMIM®:

613280 (Updated 05-Apr-2021)

UMLS symptoms related to Hypermanganesemia with Dystonia 1:


tremor; abnormality of extrapyramidal motor function; bradykinesia; muscle rigidity

Drugs & Therapeutics for Hypermanganesemia with Dystonia 1

Search Clinical Trials , NIH Clinical Center for Hypermanganesemia with Dystonia 1

Genetic Tests for Hypermanganesemia with Dystonia 1

Genetic tests related to Hypermanganesemia with Dystonia 1:

# Genetic test Affiliating Genes
1 Hypermanganesemia with Dystonia, Polycythemia, and Cirrhosis 29 SLC30A10

Anatomical Context for Hypermanganesemia with Dystonia 1

MalaCards organs/tissues related to Hypermanganesemia with Dystonia 1:

40
Liver, Globus Pallidus, Brain, Pituitary

Publications for Hypermanganesemia with Dystonia 1

Articles related to Hypermanganesemia with Dystonia 1:

(show all 13)
# Title Authors PMID Year
1
Mutations in SLC30A10 cause parkinsonism and dystonia with hypermanganesemia, polycythemia, and chronic liver disease. 6 57
22341971 2012
2
Syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia caused by mutations in SLC30A10, a manganese transporter in man. 6 57
22341972 2012
3
Hepatic cirrhosis, dystonia, polycythaemia and hypermanganesaemia--a new metabolic disorder. 6 57
18392750 2008
4
Paraparesis, hypermanganesaemia, and polycythaemia: a novel presentation of cirrhosis. 6 57
11040156 2000
5
SLC30A10 Mutation Involved in Parkinsonism Results in Manganese Accumulation within Nanovesicles of the Golgi Apparatus. 6
30272946 2019
6
Pathology of inherited manganese transporter deficiency. 57
24599576 2014
7
Manganese toxicity in a child with iron deficiency and polycythemia. 57
21596707 2011
8
Case report: a metabolic disorder presenting as pediatric manganism. 57
18087599 2007
9
Penicillamine for Hypermanganesemia With Dystonia, Polycythemia, and Cirrhosis in 2 Sisters. 61
33268559 2021
10
Hypermanganesemia with Dystonia 1: A Novel Mutation and Response to Iron Supplementation. 61
31970220 2020
11
Hypermanganesemia with dystonia, polycythemia and cirrhosis in 10 patients: Six novel SLC30A10 mutations and further phenotype delineation. 61
29193034 2018
12
Zebrafish slc30a10 deficiency revealed a novel compensatory mechanism of Atp2c1 in maintaining manganese homeostasis. 61
28692648 2017
13
Hypermanganesemia with Dystonia, Polycythemia and Cirrhosis (HMDPC) due to mutation in the SLC30A10 gene. 61
27117033 2016

Variations for Hypermanganesemia with Dystonia 1

ClinVar genetic disease variations for Hypermanganesemia with Dystonia 1:

6 (show top 50) (show all 60)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 SLC30A10 NR_046437.1(SLC30A10):n.525_533del Deletion Pathogenic 30885 rs281860285 GRCh37: 1:220101461-220101469
GRCh38: 1:219928119-219928127
2 SLC30A10 NM_018713.2(SLC30A10):c.266T>C (p.Leu89Pro) SNV Pathogenic 30886 rs281860284 GRCh37: 1:220101517-220101517
GRCh38: 1:219928175-219928175
3 SLC30A10 NR_046437.1(SLC30A10):n.796del Deletion Pathogenic 30887 rs281860288 GRCh37: 1:220101198-220101198
GRCh38: 1:219927856-219927856
4 SLC30A10 NM_018713.2(SLC30A10):c.507del (p.Pro170fs) Deletion Pathogenic 30888 rs281860287 GRCh37: 1:220101276-220101276
GRCh38: 1:219927934-219927934
5 SLC30A10 NM_018713.2(SLC30A10):c.1235del (p.Gln412fs) Deletion Pathogenic 30889 rs281860292 GRCh37: 1:220089014-220089014
GRCh38: 1:219915672-219915672
6 SLC30A10 nsv1067840 Deletion Pathogenic 38295 GRCh37: 1:219990803-220091941
GRCh38: 1:219817461-219918599
7 SLC30A10 NM_018713.2(SLC30A10):c.1046T>C (p.Leu349Pro) SNV Pathogenic 38406 rs281860291 GRCh37: 1:220089203-220089203
GRCh38: 1:219915861-219915861
8 SLC30A10 NR_046437.1(SLC30A10):n.503_613del Deletion Pathogenic 38407 rs1553313839 GRCh37: 1:220101381-220101491
GRCh38: 1:219928039-219928149
9 SLC30A10 NM_018713.2(SLC30A10):c.500T>C (p.Phe167Ser) SNV Pathogenic 38408 rs281860286 GRCh37: 1:220101283-220101283
GRCh38: 1:219927941-219927941
10 SLC30A10 NR_046437.1(SLC30A10):n.1014_1016del Deletion Pathogenic 38409 rs281860289 GRCh37: 1:220091788-220091790
GRCh38: 1:219918446-219918448
11 SLC30A10 NM_018713.2(SLC30A10):c.922C>T (p.Gln308Ter) SNV Pathogenic 38410 rs281860290 GRCh37: 1:220091633-220091633
GRCh38: 1:219918291-219918291
12 SLC30A10 NM_018713.2(SLC30A10):c.492del (p.Gly165fs) Deletion Pathogenic 375607 rs1057519590 GRCh37: 1:220101291-220101291
GRCh38: 1:219927949-219927949
13 SLC30A10 NR_046437.1(SLC30A10):n.707_764del Deletion Pathogenic 375608 rs1553313783 GRCh37: 1:220101230-220101287
GRCh38: 1:219927888-219927945
14 SLC30A10 NM_018713.3(SLC30A10):c.403C>T (p.Gln135Ter) SNV Pathogenic 997544 GRCh37: 1:220101380-220101380
GRCh38: 1:219928038-219928038
15 SLC30A10 NM_018713.2(SLC30A10):c.460C>T (p.Gln154Ter) SNV Pathogenic 375606 rs1057519589 GRCh37: 1:220101323-220101323
GRCh38: 1:219927981-219927981
16 SLC30A10 NM_018713.2(SLC30A10):c.1006C>T (p.His336Tyr) SNV Pathogenic 375609 rs770740586 GRCh37: 1:220089243-220089243
GRCh38: 1:219915901-219915901
17 SLC30A10 NM_018713.3(SLC30A10):c.*70G>A SNV Uncertain significance 874881 GRCh37: 1:220088721-220088721
GRCh38: 1:219915379-219915379
18 SLC30A10 NM_018713.3(SLC30A10):c.1399G>A (p.Gly467Arg) SNV Uncertain significance 875812 GRCh37: 1:220088850-220088850
GRCh38: 1:219915508-219915508
19 SLC30A10 NM_018713.3(SLC30A10):c.1248C>T (p.Pro416=) SNV Uncertain significance 875813 GRCh37: 1:220089001-220089001
GRCh38: 1:219915659-219915659
20 SLC30A10 NM_018713.3(SLC30A10):c.789T>C (p.Tyr263=) SNV Uncertain significance 875814 GRCh37: 1:220091766-220091766
GRCh38: 1:219918424-219918424
21 SLC30A10 NM_018713.2(SLC30A10):c.-20C>A SNV Uncertain significance 295596 rs886046003 GRCh37: 1:220101802-220101802
GRCh38: 1:219928460-219928460
22 SLC30A10 NM_018713.3(SLC30A10):c.*1088G>C SNV Uncertain significance 876766 GRCh37: 1:220087703-220087703
GRCh38: 1:219914361-219914361
23 SLC30A10 NM_018713.3(SLC30A10):c.624G>A (p.Val208=) SNV Uncertain significance 876801 GRCh37: 1:220101159-220101159
GRCh38: 1:219927817-219927817
24 SLC30A10 NM_018713.3(SLC30A10):c.482G>T (p.Gly161Val) SNV Uncertain significance 876802 GRCh37: 1:220101301-220101301
GRCh38: 1:219927959-219927959
25 SLC30A10 NM_018713.3(SLC30A10):c.*847G>A SNV Uncertain significance 873930 GRCh37: 1:220087944-220087944
GRCh38: 1:219914602-219914602
26 SLC30A10 NM_018713.3(SLC30A10):c.*630G>A SNV Uncertain significance 873931 GRCh37: 1:220088161-220088161
GRCh38: 1:219914819-219914819
27 SLC30A10 NM_018713.3(SLC30A10):c.*466A>T SNV Uncertain significance 873932 GRCh37: 1:220088325-220088325
GRCh38: 1:219914983-219914983
28 SLC30A10 NM_018713.3(SLC30A10):c.*452T>G SNV Uncertain significance 873933 GRCh37: 1:220088339-220088339
GRCh38: 1:219914997-219914997
29 SLC30A10 NM_018713.3(SLC30A10):c.*356G>A SNV Uncertain significance 873934 GRCh37: 1:220088435-220088435
GRCh38: 1:219915093-219915093
30 SLC30A10 NM_018713.3(SLC30A10):c.66C>G (p.Phe22Leu) SNV Uncertain significance 873996 GRCh37: 1:220101717-220101717
GRCh38: 1:219928375-219928375
31 SLC30A10 NM_018713.3(SLC30A10):c.*315G>A SNV Uncertain significance 874877 GRCh37: 1:220088476-220088476
GRCh38: 1:219915134-219915134
32 SLC30A10 NM_018713.3(SLC30A10):c.*172T>C SNV Uncertain significance 874878 GRCh37: 1:220088619-220088619
GRCh38: 1:219915277-219915277
33 SLC30A10 NM_018713.3(SLC30A10):c.*117G>C SNV Uncertain significance 874879 GRCh37: 1:220088674-220088674
GRCh38: 1:219915332-219915332
34 SLC30A10 NM_018713.2(SLC30A10):c.440G>C (p.Gly147Ala) SNV Uncertain significance 295592 rs886046002 GRCh37: 1:220101343-220101343
GRCh38: 1:219928001-219928001
35 SLC30A10 NM_018713.2(SLC30A10):c.676A>G (p.Met226Val) SNV Uncertain significance 295589 rs199783843 GRCh37: 1:220100412-220100412
GRCh38: 1:219927070-219927070
36 SLC30A10 NM_018713.2(SLC30A10):c.-19G>A SNV Uncertain significance 295595 rs199933401 GRCh37: 1:220101801-220101801
GRCh38: 1:219928459-219928459
37 SLC30A10 NM_018713.2(SLC30A10):c.*239A>G SNV Uncertain significance 295581 rs886046000 GRCh37: 1:220088552-220088552
GRCh38: 1:219915210-219915210
38 SLC30A10 NM_018713.2(SLC30A10):c.-68C>T SNV Uncertain significance 295598 rs886046004 GRCh37: 1:220101850-220101850
GRCh38: 1:219928508-219928508
39 SLC30A10 NM_018713.2(SLC30A10):c.1249C>G (p.Pro417Ala) SNV Uncertain significance 295584 rs757737775 GRCh37: 1:220089000-220089000
GRCh38: 1:219915658-219915658
40 SLC30A10 NM_018713.2(SLC30A10):c.907G>A (p.Ala303Thr) SNV Uncertain significance 295587 rs34097842 GRCh37: 1:220091648-220091648
GRCh38: 1:219918306-219918306
41 SLC30A10 NM_018713.2(SLC30A10):c.-70C>T SNV Uncertain significance 295599 rs886046005 GRCh37: 1:220101852-220101852
GRCh38: 1:219928510-219928510
42 SLC30A10 NM_018713.2(SLC30A10):c.1449G>A (p.Thr483=) SNV Uncertain significance 295582 rs148203711 GRCh37: 1:220088800-220088800
GRCh38: 1:219915458-219915458
43 SLC30A10 NM_018713.2(SLC30A10):c.*397C>T SNV Uncertain significance 295579 rs747429986 GRCh37: 1:220088394-220088394
GRCh38: 1:219915052-219915052
44 SLC30A10 NM_018713.2(SLC30A10):c.1118C>A (p.Ala373Glu) SNV Uncertain significance 295585 rs202111121 GRCh37: 1:220089131-220089131
GRCh38: 1:219915789-219915789
45 SLC30A10 NM_018713.2(SLC30A10):c.719-6T>C SNV Uncertain significance 295588 rs61832076 GRCh37: 1:220091842-220091842
GRCh38: 1:219918500-219918500
46 SLC30A10 NM_018713.2(SLC30A10):c.76C>G (p.Leu26Val) SNV Uncertain significance 295594 rs774149422 GRCh37: 1:220101707-220101707
GRCh38: 1:219928365-219928365
47 SLC30A10 NM_018713.2(SLC30A10):c.1068C>T (p.Asp356=) SNV Uncertain significance 295586 rs886046001 GRCh37: 1:220089181-220089181
GRCh38: 1:219915839-219915839
48 SLC30A10 NM_018713.2(SLC30A10):c.-87A>T SNV Likely benign 295600 rs531545790 GRCh37: 1:220101869-220101869
GRCh38: 1:219928527-219928527
49 SLC30A10 NM_018713.2(SLC30A10):c.284C>T (p.Thr95Ile) SNV Likely benign 295593 rs188273166 GRCh37: 1:220101499-220101499
GRCh38: 1:219928157-219928157
50 SLC30A10 NM_018713.2(SLC30A10):c.*945C>T SNV Likely benign 295577 rs115277486 GRCh37: 1:220087846-220087846
GRCh38: 1:219914504-219914504

UniProtKB/Swiss-Prot genetic disease variations for Hypermanganesemia with Dystonia 1:

72
# Symbol AA change Variation ID SNP ID
1 SLC30A10 p.Leu89Pro VAR_072573 rs281860284
2 SLC30A10 p.Leu349Pro VAR_072577 rs281860291

Expression for Hypermanganesemia with Dystonia 1

Search GEO for disease gene expression data for Hypermanganesemia with Dystonia 1.

Pathways for Hypermanganesemia with Dystonia 1

GO Terms for Hypermanganesemia with Dystonia 1

Sources for Hypermanganesemia with Dystonia 1

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
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44 MeSH
45 MESH via Orphanet
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56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
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69 Tocris
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71 UMLS via Orphanet
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