MCID: PRK069
MIFTS: 30

Parkinsonism-Dystonia, Infantile

Categories: Genetic diseases, Rare diseases, Neuronal diseases

Aliases & Classifications for Parkinsonism-Dystonia, Infantile

MalaCards integrated aliases for Parkinsonism-Dystonia, Infantile:

Name: Parkinsonism-Dystonia, Infantile 57 25 13 73
Dopamine Transporter Deficiency Syndrome 57 53 25 75
Infantile Parkinsonism-Dystonia 53 25 29 6
Pkdys 57 25 59 75
Dtds 57 25 75
Parkinsonism-Dystonia Infantile 53 75
Dopamine Transporter Deficiency Syndrome; Dtds 57
Parkinsonism-Dystonia, Infantile ) 40
Infantile Dystonia-Parkinsonism 59
Dystonia-Parkinsonism Infantile 75
Ipd 59

Characteristics:

Orphanet epidemiological data:

59
infantile dystonia-parkinsonism
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
onset in early infancy
decreased life expectancy
death often in the teenage years
poor response to l-dopa


HPO:

32
parkinsonism-dystonia, infantile:
Onset and clinical course infantile onset progressive
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 59  
Rare neurological diseases


Summaries for Parkinsonism-Dystonia, Infantile

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 238455Disease definitionInfantile dystonia-parkinsonism (IPD) is an extremely rare inherited neurological syndrome that presents in early infancy with hypokinetic parkinsonism and dystonia and that can be fatal.EpidemiologyThe prevalence is unknown. Only eight cases have been reported to date.Clinical descriptionThe disease presents soon after birth with irritability and feeding difficulties, followed by progressive parkinsonism (manifesting with resting tremor and bradykinesia), dystonia, axial hypotonia, limb hypertonicity and pyramidal tract signs. Clinically it can resemble cerebral palsy. Global developmental delay and impaired motor development occur during childhood, and patients can have trouble communicating. Treatment with L-dopa is ineffective, and death was reported in one case.EtiologyIPD is caused by mutations in the SLC6A3 gene (5p15.33), which encodes a human dopamine transporter mediating the active reuptake of extracelluar dopamine. Mutations in this gene lead to a reduction in the level of mature dopamine transporter and therefore an impairment in dopaminergic neurotransmission.Genetic counselingIPD is inherited in an autosomal recessive manner. Genetic counseling is possible and is recommended.Visit the Orphanet disease page for more resources.

MalaCards based summary : Parkinsonism-Dystonia, Infantile, also known as dopamine transporter deficiency syndrome, is related to slc6a3-related dopamine transporter deficiency syndrome and diastrophic dysplasia, and has symptoms including constipation, muscle rigidity and tremor. An important gene associated with Parkinsonism-Dystonia, Infantile is SLC6A3 (Solute Carrier Family 6 Member 3). Affiliated tissues include eye, and related phenotypes are global developmental delay and hypertonia

Genetics Home Reference : 25 Dopamine transporter deficiency syndrome is a rare movement disorder. The condition is also known as infantile parkinsonism-dystonia because the problems with movement (dystonia and parkinsonism, described below) usually start in infancy and worsen over time. However, the features of the condition sometimes do not appear until childhood or later.

OMIM : 57 Infantile parkinsonism-dystonia, also known as dopamine transporter deficiency syndrome (DTDS), is an autosomal recessive complex motor neurologic disorder with onset in infancy. Affected individuals show hyperkinesia with orolingual and limb dyskinesia, dystonia, and chorea, or hypokinesia with parkinsonian features, such as bradykinesia, rigidity, and tremor. Other features may include axial hypotonia, pyramidal tract signs, and eye movement abnormalities. Many patients are misdiagnosed as having cerebral palsy. Cognitive function appears to be less severely affected, but most patients die in the teenage years. There is no effective treatment. Laboratory studies show an increased ratio of homovanillic acid (HVA) to 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF), which represents an increase in dopamine metabolites (review by Kurian et al., 2011). For an overlapping phenotype, see tyrosine hydroxylase deficiency (605407), also known as autosomal recessive Segawa syndrome. (613135)

UniProtKB/Swiss-Prot : 75 Parkinsonism-dystonia infantile: A neurodegenerative disorder characterized by infantile onset of parkinsonism and dystonia. Other neurologic features include global developmental delay, bradykinesia and pyramidal tract signs.

Related Diseases for Parkinsonism-Dystonia, Infantile

Diseases related to Parkinsonism-Dystonia, Infantile via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 21)
# Related Disease Score Top Affiliating Genes
1 slc6a3-related dopamine transporter deficiency syndrome 12.3
2 diastrophic dysplasia 11.9
3 invasive pneumococcal disease, recurrent isolated, 1 11.4
4 invasive pneumococcal disease, recurrent isolated, 2 11.3
5 segawa syndrome, autosomal recessive 11.1
6 dystonia 10.3
7 neurodegeneration with brain iron accumulation 2a 10.0
8 personality disorder 9.9
9 paine syndrome 9.8
10 aging 9.8
11 allergic rhinitis 9.8
12 spinal stenosis 9.8
13 aphasia 9.8
14 amblyopia 9.8
15 pathological gambling 9.8
16 interstitial cystitis 9.8
17 cystitis 9.8
18 adenocarcinoma 9.8
19 rhinitis 9.8
20 peritonitis 9.8
21 rem sleep behavior disorder 9.8

Graphical network of the top 20 diseases related to Parkinsonism-Dystonia, Infantile:



Diseases related to Parkinsonism-Dystonia, Infantile

Symptoms & Phenotypes for Parkinsonism-Dystonia, Infantile

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
tremor
chorea
dyskinesia
dystonia
rigidity
more
Head And Neck Face:
masked facies

Head And Neck Mouth:
orolingual dyskinesia

Abdomen Gastrointestinal:
constipation
gastroesophageal reflux
feeding difficulties

Head And Neck Eyes:
oculogyric crises
ocular flutter
eye movement disorder

Laboratory Abnormalities:
increased csf homovanillic acid (hva)
normal csf 5-hydroxyindoleacetic acid (5-hiaa)


Clinical features from OMIM:

613135

Human phenotypes related to Parkinsonism-Dystonia, Infantile:

32 (show all 16)
# Description HPO Frequency HPO Source Accession
1 global developmental delay 32 HP:0001263
2 hypertonia 32 HP:0001276
3 parkinsonism 32 HP:0001300
4 tremor 32 HP:0001337
5 constipation 32 HP:0002019
6 gastroesophageal reflux 32 HP:0002020
7 morphological abnormality of the pyramidal tract 32 HP:0002062
8 rigidity 32 HP:0002063
9 bradykinesia 32 HP:0002067
10 chorea 32 HP:0002072
11 delayed gross motor development 32 HP:0002194
12 limb dystonia 32 HP:0002451
13 abnormal pyramidal signs 32 HP:0007256
14 muscular hypotonia of the trunk 32 HP:0008936
15 feeding difficulties 32 HP:0011968
16 dyskinesia 32 HP:0100660

UMLS symptoms related to Parkinsonism-Dystonia, Infantile:


constipation, muscle rigidity, tremor, bradykinesia, abnormal pyramidal signs, dystonia, limb

Drugs & Therapeutics for Parkinsonism-Dystonia, Infantile

Search Clinical Trials , NIH Clinical Center for Parkinsonism-Dystonia, Infantile

Genetic Tests for Parkinsonism-Dystonia, Infantile

Genetic tests related to Parkinsonism-Dystonia, Infantile:

# Genetic test Affiliating Genes
1 Infantile Parkinsonism-Dystonia 29 SLC6A3

Anatomical Context for Parkinsonism-Dystonia, Infantile

MalaCards organs/tissues related to Parkinsonism-Dystonia, Infantile:

41
Eye

Publications for Parkinsonism-Dystonia, Infantile

Articles related to Parkinsonism-Dystonia, Infantile:

# Title Authors Year
1
Pharmacological Chaperones of the Dopamine Transporter Rescue Dopamine Transporter Deficiency Syndrome Mutations in Heterologous Cells. ( 27555326 )
2016
2
Dopamine transporter deficiency syndrome: phenotypic spectrum from infancy to adulthood. ( 24613933 )
2014
3
Clinical and molecular characterisation of hereditary dopamine transporter deficiency syndrome: an observational cohort and experimental study. ( 21112253 )
2011
4
SLC6A3-Related Dopamine Transporter Deficiency Syndrome ( 28749637 )
1993

Variations for Parkinsonism-Dystonia, Infantile

UniProtKB/Swiss-Prot genetic disease variations for Parkinsonism-Dystonia, Infantile:

75
# Symbol AA change Variation ID SNP ID
1 SLC6A3 p.Leu368Gln VAR_063771 rs267607068
2 SLC6A3 p.Pro395Leu VAR_063772 rs267607069

ClinVar genetic disease variations for Parkinsonism-Dystonia, Infantile:

6
(show top 50) (show all 82)
# Gene Variation Type Significance SNP ID Assembly Location
1 SLC6A3 NM_001044.4(SLC6A3): c.1103T> A (p.Leu368Gln) single nucleotide variant Pathogenic rs267607068 GRCh37 Chromosome 5, 1414859: 1414859
2 SLC6A3 NM_001044.4(SLC6A3): c.1103T> A (p.Leu368Gln) single nucleotide variant Pathogenic rs267607068 GRCh38 Chromosome 5, 1414744: 1414744
3 SLC6A3 NM_001044.4(SLC6A3): c.1184C> T (p.Pro395Leu) single nucleotide variant Pathogenic rs267607069 GRCh37 Chromosome 5, 1411443: 1411443
4 SLC6A3 NM_001044.4(SLC6A3): c.1184C> T (p.Pro395Leu) single nucleotide variant Pathogenic rs267607069 GRCh38 Chromosome 5, 1411328: 1411328
5 SLC6A3 NM_001044.4(SLC6A3): c.1269+1G> A single nucleotide variant Pathogenic rs431905504 GRCh37 Chromosome 5, 1411357: 1411357
6 SLC6A3 NM_001044.4(SLC6A3): c.1269+1G> A single nucleotide variant Pathogenic rs431905504 GRCh38 Chromosome 5, 1411242: 1411242
7 SLC6A3 NM_001044.4(SLC6A3): c.1031+1G> A single nucleotide variant Likely pathogenic rs431905514 GRCh37 Chromosome 5, 1416212: 1416212
8 SLC6A3 NM_001044.4(SLC6A3): c.1031+1G> A single nucleotide variant Likely pathogenic rs431905514 GRCh38 Chromosome 5, 1416097: 1416097
9 SLC6A3 NM_001044.4(SLC6A3): c.671T> C (p.Leu224Pro) single nucleotide variant Pathogenic rs431905515 GRCh37 Chromosome 5, 1422112: 1422112
10 SLC6A3 NM_001044.4(SLC6A3): c.671T> C (p.Leu224Pro) single nucleotide variant Pathogenic rs431905515 GRCh38 Chromosome 5, 1421997: 1421997
11 SLC6A3 NM_001044.4(SLC6A3): c.1561C> T (p.Arg521Trp) single nucleotide variant Pathogenic rs431905516 GRCh37 Chromosome 5, 1406341: 1406341
12 SLC6A3 NM_001044.4(SLC6A3): c.1561C> T (p.Arg521Trp) single nucleotide variant Pathogenic rs431905516 GRCh38 Chromosome 5, 1406226: 1406226
13 SLC6A3 NM_001044.4(SLC6A3): c.1215A> G (p.Ser405=) single nucleotide variant Benign rs6347 GRCh37 Chromosome 5, 1411412: 1411412
14 SLC6A3 NM_001044.4(SLC6A3): c.1215A> G (p.Ser405=) single nucleotide variant Benign rs6347 GRCh38 Chromosome 5, 1411297: 1411297
15 SLC6A3 NM_001044.4(SLC6A3): c.1731C> T (p.Ala577=) single nucleotide variant Benign rs6349 GRCh37 Chromosome 5, 1403073: 1403073
16 SLC6A3 NM_001044.4(SLC6A3): c.1731C> T (p.Ala577=) single nucleotide variant Benign rs6349 GRCh38 Chromosome 5, 1402958: 1402958
17 SLC6A3 NM_001044.4(SLC6A3): c.1676C> T (p.Ala559Val) single nucleotide variant Uncertain significance rs28364997 GRCh37 Chromosome 5, 1403128: 1403128
18 SLC6A3 NM_001044.4(SLC6A3): c.1676C> T (p.Ala559Val) single nucleotide variant Uncertain significance rs28364997 GRCh38 Chromosome 5, 1403013: 1403013
19 SLC6A3 NM_001044.4(SLC6A3): c.499C> T (p.Leu167Phe) single nucleotide variant Uncertain significance rs71653633 GRCh37 Chromosome 5, 1432733: 1432733
20 SLC6A3 NM_001044.4(SLC6A3): c.499C> T (p.Leu167Phe) single nucleotide variant Uncertain significance rs71653633 GRCh38 Chromosome 5, 1432618: 1432618
21 SLC6A3 NM_001044.4(SLC6A3): c.1413C> G (p.Val471=) single nucleotide variant Benign rs8179035 GRCh37 Chromosome 5, 1409226: 1409226
22 SLC6A3 NM_001044.4(SLC6A3): c.1413C> G (p.Val471=) single nucleotide variant Benign rs8179035 GRCh38 Chromosome 5, 1409111: 1409111
23 SLC6A3 NM_001044.4(SLC6A3): c.810C> T (p.Ala270=) single nucleotide variant Benign rs6348 GRCh38 Chromosome 5, 1420686: 1420686
24 SLC6A3 NM_001044.4(SLC6A3): c.810C> T (p.Ala270=) single nucleotide variant Benign rs6348 GRCh37 Chromosome 5, 1420801: 1420801
25 SLC6A3 NM_001044.4(SLC6A3): c.546C> T (p.Asn182=) single nucleotide variant Benign/Likely benign rs28364996 GRCh37 Chromosome 5, 1432686: 1432686
26 SLC6A3 NM_001044.4(SLC6A3): c.546C> T (p.Asn182=) single nucleotide variant Benign/Likely benign rs28364996 GRCh38 Chromosome 5, 1432571: 1432571
27 SLC6A3 NM_001044.4(SLC6A3): c.60G> A (p.Glu20=) single nucleotide variant Benign rs115160598 GRCh37 Chromosome 5, 1443253: 1443253
28 SLC6A3 NM_001044.4(SLC6A3): c.60G> A (p.Glu20=) single nucleotide variant Benign rs115160598 GRCh38 Chromosome 5, 1443138: 1443138
29 SLC6A3 NM_001044.4(SLC6A3): c.1137C> T (p.Ile379=) single nucleotide variant Benign rs201605046 GRCh37 Chromosome 5, 1414825: 1414825
30 SLC6A3 NM_001044.4(SLC6A3): c.1137C> T (p.Ile379=) single nucleotide variant Benign rs201605046 GRCh38 Chromosome 5, 1414710: 1414710
31 SLC6A3 NM_001044.4(SLC6A3): c.1080C> T (p.Ser360=) single nucleotide variant Likely benign rs142241083 GRCh37 Chromosome 5, 1414882: 1414882
32 SLC6A3 NM_001044.4(SLC6A3): c.1080C> T (p.Ser360=) single nucleotide variant Likely benign rs142241083 GRCh38 Chromosome 5, 1414767: 1414767
33 SLC6A3 NM_001044.4(SLC6A3): c.1035C> T (p.Asp345=) single nucleotide variant Benign rs369288905 GRCh37 Chromosome 5, 1414927: 1414927
34 SLC6A3 NM_001044.4(SLC6A3): c.1035C> T (p.Asp345=) single nucleotide variant Benign rs369288905 GRCh38 Chromosome 5, 1414812: 1414812
35 SLC6A3 NM_001044.4(SLC6A3): c.605C> G (p.Ser202Trp) single nucleotide variant Uncertain significance rs149444784 GRCh37 Chromosome 5, 1432627: 1432627
36 SLC6A3 NM_001044.4(SLC6A3): c.605C> G (p.Ser202Trp) single nucleotide variant Uncertain significance rs149444784 GRCh38 Chromosome 5, 1432512: 1432512
37 SLC6A3 NM_001044.4(SLC6A3): c.360C> T (p.Leu120=) single nucleotide variant Likely benign rs148447720 GRCh37 Chromosome 5, 1441532: 1441532
38 SLC6A3 NM_001044.4(SLC6A3): c.360C> T (p.Leu120=) single nucleotide variant Likely benign rs148447720 GRCh38 Chromosome 5, 1441417: 1441417
39 SLC6A3 NM_001044.4(SLC6A3): c.162C> T (p.Pro54=) single nucleotide variant Benign rs6351 GRCh38 Chromosome 5, 1443036: 1443036
40 SLC6A3 NM_001044.4(SLC6A3): c.162C> T (p.Pro54=) single nucleotide variant Benign rs6351 GRCh37 Chromosome 5, 1443151: 1443151
41 SLC6A3 NM_001044.4(SLC6A3): c.114C> G (p.Asn38Lys) single nucleotide variant Uncertain significance rs6350 GRCh38 Chromosome 5, 1443084: 1443084
42 SLC6A3 NM_001044.4(SLC6A3): c.114C> G (p.Asn38Lys) single nucleotide variant Uncertain significance rs6350 GRCh37 Chromosome 5, 1443199: 1443199
43 SLC6A3 NM_001044.4(SLC6A3): c.1843C> T (p.Arg615Cys) single nucleotide variant Uncertain significance rs763131939 GRCh37 Chromosome 5, 1394870: 1394870
44 SLC6A3 NM_001044.4(SLC6A3): c.1843C> T (p.Arg615Cys) single nucleotide variant Uncertain significance rs763131939 GRCh38 Chromosome 5, 1394755: 1394755
45 SLC6A3 NM_001044.4(SLC6A3): c.1036G> A (p.Ala346Thr) single nucleotide variant Uncertain significance rs375720650 GRCh37 Chromosome 5, 1414926: 1414926
46 SLC6A3 NM_001044.4(SLC6A3): c.1036G> A (p.Ala346Thr) single nucleotide variant Uncertain significance rs375720650 GRCh38 Chromosome 5, 1414811: 1414811
47 SLC6A3 NM_001044.4(SLC6A3): c.150G> T (p.Pro50=) single nucleotide variant Benign rs6346 GRCh37 Chromosome 5, 1443163: 1443163
48 SLC6A3 NM_001044.4(SLC6A3): c.150G> T (p.Pro50=) single nucleotide variant Benign rs6346 GRCh38 Chromosome 5, 1443048: 1443048
49 SLC6A3 NM_001044.4(SLC6A3): c.1527G> A (p.Gln509=) single nucleotide variant Benign rs6880875 GRCh38 Chromosome 5, 1406260: 1406260
50 SLC6A3 NM_001044.4(SLC6A3): c.1527G> A (p.Gln509=) single nucleotide variant Benign rs6880875 GRCh37 Chromosome 5, 1406375: 1406375

Expression for Parkinsonism-Dystonia, Infantile

Search GEO for disease gene expression data for Parkinsonism-Dystonia, Infantile.

Pathways for Parkinsonism-Dystonia, Infantile

GO Terms for Parkinsonism-Dystonia, Infantile

Sources for Parkinsonism-Dystonia, Infantile

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7 CNVD
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58 OMIM via Orphanet
62 PubMed
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69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
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74 UMLS via Orphanet
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