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 53 24 13 69
Dopamine Transporter Deficiency Syndrome 53 49 24 71
Pkdys 53 24 55 71
Infantile Parkinsonism-Dystonia 49 24 28
Dtds 53 24 71
Parkinsonism-Dystonia Infantile 49 71
Dopamine Transporter Deficiency Syndrome; Dtds 53
Infantile Dystonia-Parkinsonism 55
Dystonia-Parkinsonism Infantile 71
Ipd 55

Characteristics:

Orphanet epidemiological data:

55
infantile dystonia-parkinsonism
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

53
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:

31
parkinsonism-dystonia, infantile:
Onset and clinical course infantile onset progressive
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 55  
Rare neurological diseases


Summaries for Parkinsonism-Dystonia, Infantile

NIH Rare Diseases : 49 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. Last updated: 11/1/2013

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, tremor and bradykinesia. An important gene associated with Parkinsonism-Dystonia, Infantile is SLC6A3 (Solute Carrier Family 6 Member 3). Affiliated tissues include eye.

OMIM : 53 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 : 71 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.

Genetics Home Reference : 24 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.

Related Diseases for Parkinsonism-Dystonia, Infantile

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:

53
Abdomen Gastroin testinal:
constipation
gastroesophageal reflux
feeding difficulties

Head And Neck Face:
masked facies

Head And Neck Mouth:
orolingual dyskinesia

Neurologic Central Nervous System:
tremor
dystonia
bradykinesia
chorea
dyskinesia
more
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:

31 (show all 16)
# Description HPO Frequency HPO Source Accession
1 constipation 31 HP:0002019
2 tremor 31 HP:0001337
3 bradykinesia 31 HP:0002067
4 abnormal pyramidal signs 31 HP:0007256
5 chorea 31 HP:0002072
6 global developmental delay 31 HP:0001263
7 dyskinesia 31 HP:0100660
8 hypertonia 31 HP:0001276
9 gastroesophageal reflux 31 HP:0002020
10 feeding difficulties 31 HP:0011968
11 rigidity 31 HP:0002063
12 delayed gross motor development 31 HP:0002194
13 parkinsonism 31 HP:0001300
14 limb dystonia 31 HP:0002451
15 muscular hypotonia of the trunk 31 HP:0008936
16 morphological abnormality of the pyramidal tract 31 HP:0002062

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 28 SLC6A3

Anatomical Context for Parkinsonism-Dystonia, Infantile

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

38
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:

71
# 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
# 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.1184C> T (p.Pro395Leu) single nucleotide variant Pathogenic rs267607069 GRCh37 Chromosome 5, 1411443: 1411443
3 SLC6A3 NM_001044.4(SLC6A3): c.1269+1G> A single nucleotide variant Pathogenic rs431905504 GRCh37 Chromosome 5, 1411357: 1411357
4 SLC6A3 NM_001044.4(SLC6A3): c.1031+1G> A single nucleotide variant Pathogenic/Likely pathogenic rs431905514 GRCh37 Chromosome 5, 1416212: 1416212
5 SLC6A3 NM_001044.4(SLC6A3): c.671T> C (p.Leu224Pro) single nucleotide variant Pathogenic rs431905515 GRCh37 Chromosome 5, 1422112: 1422112
6 SLC6A3 NM_001044.4(SLC6A3): c.1561C> T (p.Arg521Trp) single nucleotide variant Pathogenic rs431905516 GRCh37 Chromosome 5, 1406341: 1406341

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

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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