PKDYS
MCID: PRK101
MIFTS: 32

Parkinsonism-Dystonia, Infantile, 1 (PKDYS)

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

Aliases & Classifications for Parkinsonism-Dystonia, Infantile, 1

MalaCards integrated aliases for Parkinsonism-Dystonia, Infantile, 1:

Name: Parkinsonism-Dystonia, Infantile, 1 58
Pkdys 58 54 26 60 76
Dopamine Transporter Deficiency Syndrome 58 54 26 76
Infantile Parkinsonism-Dystonia 54 26 30 6
Dtds 58 54 26 76
Parkinsonism-Dystonia, Infantile 26 13
Parkinsonism-Dystonia Infantile 54 76
Slc6a3-Related Dopamine Transporter Deficiency Syndrome 54
Dopamine Transporter Deficiency Syndrome; Dtds 58
Parkinsonism-Dystonia, Infantile ) 41
Infantile Dystonia-Parkinsonism 60
Dystonia-Parkinsonism Infantile 76
Dat Deficiency 54
Pkdys1 58
Ipd 60

Characteristics:

Orphanet epidemiological data:

60
infantile dystonia-parkinsonism
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

58
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:

33
parkinsonism-dystonia, infantile, 1:
Onset and clinical course infantile onset progressive
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 60  
Rare neurological diseases


Summaries for Parkinsonism-Dystonia, Infantile, 1

NIH Rare Diseases : 54 Dopamine transporter deficiency syndrome (DTDS) is a rare movement disorder that causes progressive (worsening) dystonia and parkinsonism. It usually begins in infancy ('classic DTDS') and for this reason, it is also known as 'infantile parkinsonism dystonia.' However, some people with DTDS may not develop symptoms until childhood or later (which is known as 'atypical DTDS'). The dystonia in DTDS is characterized by uncontrollable (involuntary), long-lasting muscle contractions and cramps that involve many different muscles. Dystonia causes difficulty with daily activities and impairs the ability to talk, eat, drink, pick up objects, and walk. Parkinsonism develops as the disorder progresses and is characterized by tremor (shaking), slowed movements (bradykinesia), rigidity (stiffness), and impaired balance and coordination. Additional symptoms that may be present include abnormal eye movements, reduced facial expressions, irritability, sleeping problems, digestive problems (such as reflux or constipation), and recurrent pneumonia which can be life-threatening. Classic DTDS is associated with a poor outlook (prognosis), and death may occur in the teenage years due to unexplained sudden causes or respiratory complications. Those with atypical DTDS may have milder symptoms and a longer lifespan, but the long-term outlook for this form is not well-known. DTDS is caused by mutations in the SLC6A3 gene and inheritance is autosomal recessive. There is no cure for DTDS; treatment aims to relieve symptoms and increase quality of life. Treatment may include medicines to control involuntary movements (such as tetrabenazine and benzodiazepines), medicines to control dystonia (such as pramipexole and ropinirole), and physical therapy to reduce the risk of contractures from muscle rigidity.

MalaCards based summary : Parkinsonism-Dystonia, Infantile, 1, also known as pkdys, is related to slc6a3-related dopamine transporter deficiency syndrome and diastrophic dysplasia, and has symptoms including tremor, constipation and abnormal pyramidal signs. An important gene associated with Parkinsonism-Dystonia, Infantile, 1 is SLC6A3 (Solute Carrier Family 6 Member 3). Affiliated tissues include eye, and related phenotypes are parkinsonism and constipation

Genetics Home Reference : 26 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 : 58 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 increased ratio of dopamine to serotonin metabolites (review by Kurian et al., 2011). (613135)

UniProtKB/Swiss-Prot : 76 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, 1

Graphical network of the top 20 diseases related to Parkinsonism-Dystonia, Infantile, 1:



Diseases related to Parkinsonism-Dystonia, Infantile, 1

Symptoms & Phenotypes for Parkinsonism-Dystonia, Infantile, 1

Human phenotypes related to Parkinsonism-Dystonia, Infantile, 1:

60 33 (show all 29)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 parkinsonism 60 33 hallmark (90%) Very frequent (99-80%) HP:0001300
2 constipation 60 33 frequent (33%) Frequent (79-30%) HP:0002019
3 chorea 60 33 frequent (33%) Frequent (79-30%) HP:0002072
4 global developmental delay 60 33 frequent (33%) Frequent (79-30%) HP:0001263
5 gastroesophageal reflux 60 33 frequent (33%) Frequent (79-30%) HP:0002020
6 irritability 60 33 frequent (33%) Frequent (79-30%) HP:0000737
7 feeding difficulties 60 33 frequent (33%) Frequent (79-30%) HP:0011968
8 absent speech 60 33 frequent (33%) Frequent (79-30%) HP:0001344
9 cerebral palsy 60 33 frequent (33%) Frequent (79-30%) HP:0100021
10 bradykinesia 60 33 frequent (33%) Frequent (79-30%) HP:0002067
11 hypokinesia 60 33 frequent (33%) Frequent (79-30%) HP:0002375
12 hypomimic face 60 33 frequent (33%) Frequent (79-30%) HP:0000338
13 oculogyric crisis 60 33 frequent (33%) Frequent (79-30%) HP:0010553
14 muscular hypotonia of the trunk 60 33 frequent (33%) Frequent (79-30%) HP:0008936
15 orofacial dyskinesia 60 33 frequent (33%) Frequent (79-30%) HP:0002310
16 limb hypertonia 60 33 frequent (33%) Frequent (79-30%) HP:0002509
17 abnormal pyramidal sign 33 frequent (33%) HP:0007256
18 abnormal circulating carboxylic acid concentration 33 frequent (33%) HP:0004354
19 hypertonia 60 33 Frequent (79-30%) HP:0001276
20 tremor 33 HP:0001337
21 abnormal pyramidal signs 60 Frequent (79-30%)
22 dyskinesia 33 HP:0100660
23 dystonia 60 Very frequent (99-80%)
24 rigidity 33 HP:0002063
25 delayed gross motor development 33 HP:0002194
26 limb dystonia 33 HP:0002451
27 abnormality of carboxylic acid metabolism 60 Frequent (79-30%)
28 morphological abnormality of the pyramidal tract 33 HP:0002062
29 ocular flutter 33 HP:0031931

Symptoms via clinical synopsis from OMIM:

58
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

UMLS symptoms related to Parkinsonism-Dystonia, Infantile, 1:


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

Drugs & Therapeutics for Parkinsonism-Dystonia, Infantile, 1

Search Clinical Trials , NIH Clinical Center for Parkinsonism-Dystonia, Infantile, 1

Genetic Tests for Parkinsonism-Dystonia, Infantile, 1

Genetic tests related to Parkinsonism-Dystonia, Infantile, 1:

# Genetic test Affiliating Genes
1 Infantile Parkinsonism-Dystonia 30 SLC6A3

Anatomical Context for Parkinsonism-Dystonia, Infantile, 1

MalaCards organs/tissues related to Parkinsonism-Dystonia, Infantile, 1:

42
Eye

Publications for Parkinsonism-Dystonia, Infantile, 1

Articles related to Parkinsonism-Dystonia, Infantile, 1:

# 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, 1

UniProtKB/Swiss-Prot genetic disease variations for Parkinsonism-Dystonia, Infantile, 1:

76
# 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, 1:

6 (show top 50) (show all 92)
# Gene Variation Type Significance SNP ID Assembly Location
1 SLC6A3 NM_001044.4(SLC6A3): c.1215A> G (p.Ser405=) single nucleotide variant Benign rs6347 GRCh37 Chromosome 5, 1411412: 1411412
2 SLC6A3 NM_001044.4(SLC6A3): c.1215A> G (p.Ser405=) single nucleotide variant Benign rs6347 GRCh38 Chromosome 5, 1411297: 1411297
3 SLC6A3 NM_001044.4(SLC6A3): c.1103T> A (p.Leu368Gln) single nucleotide variant Pathogenic rs267607068 GRCh37 Chromosome 5, 1414859: 1414859
4 SLC6A3 NM_001044.4(SLC6A3): c.1103T> A (p.Leu368Gln) single nucleotide variant Pathogenic rs267607068 GRCh38 Chromosome 5, 1414744: 1414744
5 SLC6A3 NM_001044.4(SLC6A3): c.1184C> T (p.Pro395Leu) single nucleotide variant Pathogenic rs267607069 GRCh37 Chromosome 5, 1411443: 1411443
6 SLC6A3 NM_001044.4(SLC6A3): c.1184C> T (p.Pro395Leu) single nucleotide variant Pathogenic rs267607069 GRCh38 Chromosome 5, 1411328: 1411328
7 SLC6A3 NM_001044.4(SLC6A3): c.1269+1G> A single nucleotide variant Pathogenic rs431905504 GRCh37 Chromosome 5, 1411357: 1411357
8 SLC6A3 NM_001044.4(SLC6A3): c.1269+1G> A single nucleotide variant Pathogenic rs431905504 GRCh38 Chromosome 5, 1411242: 1411242
9 SLC6A3 NM_001044.4(SLC6A3): c.1031+1G> A single nucleotide variant Likely pathogenic rs431905514 GRCh37 Chromosome 5, 1416212: 1416212
10 SLC6A3 NM_001044.4(SLC6A3): c.1031+1G> A single nucleotide variant Likely pathogenic rs431905514 GRCh38 Chromosome 5, 1416097: 1416097
11 SLC6A3 NM_001044.4(SLC6A3): c.671T> C (p.Leu224Pro) single nucleotide variant Pathogenic rs431905515 GRCh37 Chromosome 5, 1422112: 1422112
12 SLC6A3 NM_001044.4(SLC6A3): c.671T> C (p.Leu224Pro) single nucleotide variant Pathogenic rs431905515 GRCh38 Chromosome 5, 1421997: 1421997
13 SLC6A3 NM_001044.4(SLC6A3): c.1561C> T (p.Arg521Trp) single nucleotide variant Pathogenic rs431905516 GRCh37 Chromosome 5, 1406341: 1406341
14 SLC6A3 NM_001044.4(SLC6A3): c.1561C> T (p.Arg521Trp) single nucleotide variant Pathogenic rs431905516 GRCh38 Chromosome 5, 1406226: 1406226
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 GRCh38 Chromosome 5, 1432618: 1432618
20 SLC6A3 NM_001044.4(SLC6A3): c.499C> T (p.Leu167Phe) single nucleotide variant Uncertain significance rs71653633 GRCh37 Chromosome 5, 1432733: 1432733
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 GRCh38 Chromosome 5, 1441417: 1441417
38 SLC6A3 NM_001044.4(SLC6A3): c.360C> T (p.Leu120=) single nucleotide variant Likely benign rs148447720 GRCh37 Chromosome 5, 1441532: 1441532
39 SLC6A3 NM_001044.4(SLC6A3): c.162C> T (p.Pro54=) single nucleotide variant Benign rs6351 GRCh37 Chromosome 5, 1443151: 1443151
40 SLC6A3 NM_001044.4(SLC6A3): c.162C> T (p.Pro54=) single nucleotide variant Benign rs6351 GRCh38 Chromosome 5, 1443036: 1443036
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, 1

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Pathways for Parkinsonism-Dystonia, Infantile, 1

GO Terms for Parkinsonism-Dystonia, Infantile, 1

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